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Gum Arabic as a Phytochemical Construct for the Stabilization of Gold Nanoparticles: In Vivo Pharmacokinetics and X-ray-Contrast-Imaging Studies
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Abstract
Gold nanoparticles (AuNPs) have exceptional stability against oxidation and therefore will play a significant role in the advancement of clinically useful diagnostic and therapeutic nanomedicines. Despite the huge potential for a new generation of AuNP-based nanomedicinal products, nontoxic AuNP constructs and formulations that can be readily administered site-specifically through the intravenous mode, for diagnostic imaging by computed tomography (CT) or for therapy via various modalities, are still rare. Herein, we report results encompassing: 1) the synthesis and stabilization of AuNPs within the nontoxic phytochemical gum-arabic matrix (GA-AuNPs); 2) detailed in vitro analysis and in vivo pharmacokinetics studies of GA-AuNPs in pigs to gain insight into the organ-specific localization of this new generation of AuNP vector, and 3) X-ray CT contrast measurements of GA-AuNP vectors for potential utility in molecular imaging. Our results demonstrate that naturally occurring GA can be used as a nontoxic phytochemical construct in the production of readily administrable biocompatible AuNPs for diagnostic and therapeutic applications in nanomedicine.
... The utilization of AuNPs for drug administration is of extreme importance owing to their claimed biocompatibility and non-cytotoxicity [79][80][81]. Additionally, metal nanoparticles exhibit lower toxicity compared to other substances. ...
... The utilization of AuNPs for drug administration is of extreme importance o their claimed biocompatibility and non-cytotoxicity [79][80][81]. Additionally, met particles exhibit lower toxicity compared to other substances. ...
The rapid advancements in nanotechnology in the field of nanomedicine have the potential to significantly enhance therapeutic strategies for cancer treatment. There is considerable promise for enhancing the efficacy of cancer therapy through the manufacture of innovative nanocomposite materials. Metallic nanoparticles have been found to enhance the release of anticancer medications that are loaded onto them, resulting in a sustained release, hence reducing the dosage required for drug administration and preventing their buildup in healthy cells. The combination of nanotechnology with biocompatible materials offers new prospects for the development of advanced therapies that exhibit enhanced selectivity, reduced adverse effects, and improved patient outcomes. Chitosan (CS), a polysaccharide possessing distinct physicochemical properties, exhibits favorable attributes for controlled drug delivery due to its biocompatibility and biodegradability. Chitosan nanocomposites exhibit heightened stability, improved biocompatibility, and prolonged release characteristics for anticancer medicines. The incorporation of gold (Au) nanoparticles into the chitosan nanocomposite results in the manifestation of photothermal characteristics, whereas the inclusion of silver (Ag) nanoparticles boosts the antibacterial capabilities of the synthesized nanocomposite. The objective of this review is to investigate the recent progress in the utilization of Ag and Au nanoparticles, or a combination thereof, within a chitosan matrix or its modified derivatives for the purpose of anticancer drug delivery. The research findings for the potential of a chitosan nanocomposite to deliver various anticancer drugs, such as doxorubicin, 5-Fluroacil, curcumin, paclitaxel, and 6-mercaptopurine, were investigated. Moreover, various modifications carried out on the chitosan matrix phase and the nanocomposite surfaces to enhance targeting selectivity, loading efficiency, and pH sensitivity were highlighted. In addition, challenges and perspectives that could motivate further research related to the applications of chitosan nanocomposites in cancer therapy were summarized.
... Processing high-atomic-number materials to the nanoscale, characterizing and modifying these materials for different anatomical sites and diseases, and preparing nanotargeted reagents to achieve these five properties are now the primary focus of research into nano-CT contrast agents. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] Iodine nanometer Ct contrast agents Nanoscale iodinated contrast agents, such as micelles, polymers, and liposomes, have been increasingly developed based on their EPR in solid tumors in nano-formulations and surface modifiability to meet clinical needs for CT diagnostic contrast agents. [8][9][10][11][12] Iodine nanoparticles (NPs) offer numerous research opportunities, one of which is the development of iodine nanoliposome contrast agents. ...
... Gold (Au) nanomaterials have been extensively studied and used in the biomedical field owing to their chemical inertness, oxidation resistance, and excellent biocompatibility. 18 Au has a higher X-ray absorption capacity and provides a contrast effect per unit mass 20 utilized Au NPs encapsulated in natural gum Arabic (GA-AuNPs), they observed their high biocompatibility and stability, as indicated by the stability of the Au content remaining stable within 72 h of injection. ...
X-ray computed tomography (CT) and magnetic resonance (MR) imaging are essential tools in modern medical diagnosis and treatment. However, traditional contrast agents are inadequate in the diagnosis of various health conditions. Consequently, the development of targeted nano-contrast agents has become a crucial area of focus in the development of medical image-enhancing contrast agents. To fully understand the current development of nano-contrast agents, this review provides an overview of the preparation methods and research advancements in CT nano-contrast agents, MR nano-contrast agents, and CT/MR multimodal nano-contrast agents described in previous publications. Due to the physicochemical properties of nanomaterials, such as self-assembly and surface modifiability, these specific nano-contrast agents can greatly improve the targeting of lesions through various preparation methods and clearly highlight the distinction between lesions and normal tissues in both CT and MR. As a result, they have the potential to be used in the early stages of disease to improve diagnostic capacity and level in medical imaging.
... various bioactive and therapeutic phytochemicals from a plethora of plants. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Recent investigations have revealed that encapsulation of phytochemicals on gold nanoparticle surface not only enhances their bioavailability in vivo but the optimum size(s) of phytochemical(s) embedded gold nanoparticles allows target-specific delivery of phytochemicalsthus affording both selectivity and effective bioavailability. 15,16,[22][23][24][25] In continuation of efforts to expand the rich therapeutic potential of phytochemicals from the plant kingdom, we have now focused on the utility of Yucca genus plants which consist of approximately 50 species of the Asparagaceae family, widespread in the southwestern United States, Mexico, and in the Caribbean. ...
... Incorporation of gum arabic on the gold nanoparticulate surface affords optimum in vitro and in vivo stability against agglomeration under the complex biological in vivo conditions. 2,14,15,[18][19][20][54][55][56][57][58][59] As we have utilized nanotechnology to encapsulate Ayurvedically-relevant phytochemicals from Y. filamentosa, we have coined the term nano-Ayurvedic medicine for this medical approach. The US Patents and Trademarks office has recently granted the first ever patent for our invention on nano-Ayurvedic medicine. ...
Purpose
We report an innovative green nanotechnology utilizing an electron-rich cocktail of phytochemicals from Yucca filamentosa L. to synthesize biocompatible gold nanoparticles without the use of any external chemical reducing agents and evaluate their anti-cancer activity.
Methods
Yucca filamentosa L. extract, containing a cocktail of phytochemicals, was prepared, and used to transform gold salt into Y. filamentosa phytochemicals encapsulated gold nanoparticles (YF-AuNPs). Additionally, gum arabic stabilized YF-AuNPs (GAYF-AuNPs) were also prepared to enhance the in vitro/in vivo stability. Anticancer activity was evaluated against prostate (PC-3) and breast (MDAMB-231) cancer cell lines. Targeting abilities of gold nanoparticles were tested using pro-tumor macrophage cell lines.
Results
Comprehensive characterization of new nanomedicine agents YF-AuNPs and GAYF-AuNPs revealed spherical, and monodisperse AuNPs with moderate zeta potentials (−19 and −20 mV, respectively), indicating in vitro/in vivo stability. The core size of YF-AuNPs (14 ± 5 nm) and GAYF-AuNPs (10 ± 5 nm) is suitable for optimal penetration into tumor cells through both enhanced permeability and retention (EPR) effect as well as through the receptor mediated endocytosis. Notably, YF-AuNPs exhibited potent anticancer activity against prostate (PC-3) and breast tumors (MDAMB-231) by inducing early and late apoptotic stages. Moreover, YF-AuNPs resulted in elevated levels of anti-tumor cytokines (TNF-α and IL-12) and reduced levels of pro-tumor cytokines (IL-6 and IL-10), provide compelling evidence on the immunomodulatory property of YF-AuNPs.
Conclusion
Overall, these Y. filamentosa phytochemicals functionalized nano-Ayurvedic medicine agents demonstrated selective toxicity to cancer cells while sparing normal cells. Most notably, to our knowledge, this is the first study that shows YF-AuNP’s targeting efficacy toward pro-tumor macrophage cell lines, suggesting an immunomodulatory pathway for cancer treatment. This work introduces a novel avenue for herbal and nano-Ayurvedic approaches to human cancer treatment, mediated through selective efficacy and immunomodulatory potential.
... Surface-modified nanoparticles are utilized for imaging purposes. Hybrid nanocrystals consisting of Fe3O4 and MnO are utilized for T1-and T2-weighted MR imaging with dual contrast agents [32]. Due to their greater selectivity, improved in vitro and in use stability, and longer half-life in circulation, gold NPs are the most beneficial. ...
... Compared to the regularly used iodine contrast agent iopromide, PEG-coated NPs administered intravenously into rats had a substantially longer blood circulation period (> 4 h). Researchers found that injecting PEG NPs intravenously into hepatoma-bearing rats increased the contrast between the cancerous and healthy liver tissue [31] [32]. The ligand exchange approach was used to make these PEG-coated NPs. ...
In recent years, Nanoparticles (NPs) have gotten a lot of attention because of their multifunctionality, multivalency, and the capacity to carry payloads. Metal nano-particles (MNPs) are of current interest for their promising uses in biomedical imaging technologies for many diseases including cancer. The charge, shape, size, and hydrophilicity of MNPs are still critical for their successful distribution to their target sites in the human body. Imaging in the biomedical field are increasingly relying on nanomaterials (NMs) including nanoparticles, nanorods, and nanospheres. Metal oxide NPs (MONs) are extensively employed in functional imaging, treatment and synergistic combinational platforms. MRI, PET, CT, SPECT, and US imaging are the imaging methods in both clinical areas. There are many studies underway to improve the performance of imaging methods in complicated settings due to the necessity for reliable imaging of tiny biological targets. This review extensively discussed utilization of MONs in several bio imaging techniques.
... Synthesis of AgNPs Using P. emblica Fruit Extracts by [74] The study by Musam and co-workers (2019) reported the synthesis of AgNPs using P. emblica fruit extracts [74]. The fresh fruit extracts of P. emblica plants were prepared by following a procedure reported by [75]. Briefly, the fresh fruits were cleaned with sterilized double-deionized water and then chopped into small pieces, after which the seeds were removed. ...
... UV-visible was used to monitor the absorption spectra of the NPs to determine the stability of the NPs. In other studies by Kattumuri and co-workers (2007) [75], the introduction of an electrolyte method was used to study the stability of AuNPs produced using gum Arabic. Moreover, zeta-potentiometry was also used to provide the stability information of AuNPs because AuNPs with low surface charge tend to agglomerate, and over time the NPs gained a stable state. ...
Nanoparticles and nanotechnology developments continue to advance the livelihood of humankind. However, health challenges due to microorganisms and cancerous cells continue to threaten many people’s lives globally. Therefore, new technological interventions are of great importance. The phytochemicals present in medicinal plants are suggested as biocompatible, cost-effective, and regenerative sources that can be utilized for the green synthesis of nanoparticles. Different plant extracts with various phytochemical constituents can form nanoparticles with specific shapes, sizes, and optical properties. This review focuses on advances in green nanotechnology and provides details on reliable synthetic routes toward medically and biocompatible relevant metallic nanoparticles. We cover a wide range of applications that use phytonanoparticles with an in-depth look at what makes these materials interesting. The study also provides details of the literature on the interventions made in phytonanotechnology for the production of plant-mediated synthesis and capped metallic nanoparticles and their applications in various industries. It was observed that a variety of plants have been well studied, and detailed findings have been reported; however, the study of Phyllanthus is still in its early stages, and more needs to be uncovered.
... Many di↵erent types of polymeric NPs have been developed as contrast agents in the literature. They may be sub-classified as dendrimers [65,66], nanocapsules [67], nanotubes [68] or polymer-coated NPs [69][70][71]. ...
... On the other hand, the coating of inorganic nanoparticles with macromolecules like polymers is a definite necessity in order to stabilize the NPs suspension, to prevent the fast recognition by immune system, by also to induce a specific targeting with the appropriate functionalization. More than half of the published example for that purpose of X-ray imaging concerns gold nanoparticles [80] since they have excellent X-ray attenuation properties and they are considered to be biocompatible and nontoxic in vivo [70,[82][83][84][85][86][87][88]. Coated gold nanoparticles found numerous application for targeted imaging, here is a panel of the representative examples and possibilities. ...
La micro-tomodensitométrie à rayons X (dite micro-CT, CT = Computed Tomography), est une technique d’imagerie de haute résolution qui consiste d’une part à mesurer l’absorption des rayons X par les tissus, et d’autre part de reconstruire les images et les structures anatomiques en 3 dimensions par traitement informatique. L’agent de contraste est une substance capable d’améliorer la visibilité des structures d’un organe ou d’un liquide organique in vivo. Ce travail de thèse a eu pour objectif le développement d’agents de contraste iodés sous formes de nano-émulsions pour des applications précliniques en imagerie biomédicale. Nous nous sommes proposés d’étudier d’une part des nano-émulsions iodées afin d’avoir une longue rémanence vasculaire in vivo, une meilleure biocompatibilité et d’autre part de mettre au point une synthèse et une formulation plus simples que celles des agents de contraste nanoparticulaires commercialisés. Trois différentes huiles iodées ont été synthétisées et utilisées comme partie contrastante dans les nano-émulsions. Enfin, les nano-émulsions de l’α-tocophérol iodé nous ont permis d’atteindre l’objectif de cette thèse. Ces nano-émulsions iodées ont montré une très bonne biocompatibilité et combinent à la fois les propriétés d’un agent de contraste à longue rémanence vasculaire et un agent de contraste spécifique du foie.
... The high Z element concentration in NMOFs made them a suitable choice for CT contrast agents [67]. Regarding contrast materials in CT imaging, gold nanoparticles are preferred due to their high absorption of X-rays coefficient [68,69]. Shang et al., [70] developed tiny core-shell nanoparticles known as Au@MIL-88 (Fe). ...
... In a clinical trial, gum arabic ointment significantly reduced peristomal skin inflammation compared to the control group [41,42]. Besides, gum arabic-gold nanoparticles displayed potential for melanoma treatment [43]. ...
Melanoma is the most deadly skin disease; due to side effects and drug resistance, the development of natural medicines using nanotechnology has received much attention. This study proposed a two-step process for preparing chitosan-gum arabic nanoparticles loaded with menthol. Chitosan-gum arabic nanoparticles with a particle size of 53 ± 5 nm and zeta potential 37 ± 2 mV and chitosan-gum arabic containing menthol with a particle size of 160 ± 15 nm and zeta potential 43 ± 4 mV were prepared. Successful preparation and loading of menthol in nanoparticles were confirmed using ATR-FTIR and GC–MS analyses. Besides, their cytotoxic effects were investigated on A-375 melanoma cells; their IC50 values were 74 (41–140) µg/mL and 29 (17–38) µg/mL. The high efficiency of the developed carrier (chitosan-gum arabic nanoparticles) and chitosan-gum arabic nanoparticles containing menthol makes them suitable candidates for further consideration and in vivo research.
... The MTT assay follows the calorimetric approach, and it is used to evaluate the cyto-viability at more sites. A previous study has assessed the silica NPs 15 nm in size in a dose-dependent manner for breast cancer where the 3-(4,5-dimethylthiazol-2-yl)− 2,5-diphenyltetrazolium bromide (MTT) used, and which turn into dark blue color Formazan indicated the reduced cell viability [143]. The MTT assay was also used to assess the mitochondrial activity and cell integrity for the efficacy of the drugs [144]. ...
This article is an overview of the current state of nanoparticles because of their emerging usage in cancer treatment, covering nanoparticles that have been authorized for use in cancer therapy currently undergoing clinical testing. Recent advances in nanoparticle engineering, coupled with an enhanced understanding of critical nanoparticle attributes (size, shape, and surface properties) in conjunction with biological systems, present novel prospects for therapeutic nanoparticle development. Although inorganic and metallic nanoparticles are gaining recognition in clinical studies due to their potential usefulness but nanomaterials primarily polymeric, liposomal, and nano crystal based dominate the cancer therapy. Polymeric nanoparticles (NPs) contain specific ligands, such as polyglycolic acid (PGA) and polylactic acid (PLA), which have a chemical affinity for malignant cells and target tumors. Nanocrystals stand out with their high loading efficiency, stability, extended drug release, and capacity to deliver poorly soluble medications. The limitations of conventional chemotherapy are overcome in a variety of applications for improved cancer care by metal-based nanoparticles, either used alone or in combination. The dynamic nature of nanotechnology drives continued developments like protein-based nanoparticles and micelles. Polymer and lipid encapsulation within nanocrystals is becoming more and more popular, suggesting a long-term trend. This advancement marks a significant breakthrough in life-saving nanotechnology, particularly in cancer treatment, and sets the stage for pioneering applications in nanomedicine.
... A research was demonstrated that naturally occurring GA can be used as a nontoxic phytochemical construct in the production of readily administrable biocompatible AuNPs for diagnostic and therapeutic applications in nanomedicine [32]. AuNPs-based contrast agents may be useful in x-raybased computed tomography [6]. ...
Metformin is commonly prescribed to people with diabetes. Metformin has been shown in previous studies to be able to prevent the growth of cancer cells. This study aims to investigate the effects of metformin and gold nanoparticles in MCF7 breast cancer and A549 lung cell lines. The effects of metformin and gold nanoparticles on MCF7 breast cancer and A549 lung cells were determined on cells grown in 24 h cell culture. MCF-7 and A549 cells were incubated for 24 h with the treatment of escalating molar concentrations of ifosfamide. The MTT assay was used to determine the cytotoxicity of metformin toward MCF7 and A549 cell lines. The expression of Bax, BCL2, PI3K, Akt3, mTOR, Hsp60, Hsp70, and TNF-α was measured by RT-PCR. Metformin and gold nanoparticles inhibited the proliferation of MCF-7 and A549 cells in a dose and time-dependent manner with an IC50 value of 5 µM and 10 µg/mL. RT-PCR assays showed ifosfamide + metformin + gold nanoparticles significantly reduced the expression of BCL2, PI3K, Akt3, mTOR, Hsp60 and Hsp70 and increased the expression of TNF-α and Bax. The findings obtained in this study suggest that further studies should be conducted, and metformin and gold nanoparticles can be used in breast cancer and lung cancer treatments.
... Gum Arabic (GA), one of the natural polymers, is non-toxic, water-soluble, and vastly used in the stabilization of the food and pharmaceutical industries [23]. Its structure contains charged amine and carboxyl groups that can physically adsorb into the nanoparticle surface when used as a stabilizer [24,25]. ...
Background An innovative intracanal medication formulation was introduced in the current study to improve the calcium hydroxide (Ca(OH) 2) therapeutic capability against resistant Enterococcus faecalis (E. faecalis) biofilm. This in-vitro study aimed to prepare, characterize, and evaluate the antibacterial efficiency of Ca(OH) 2 loaded on Gum Arabic (GA) nanocarrier (Ca(OH) 2-GA NPs) and to compare this efficiency with conventional Ca(OH) 2 , Ca(OH) 2 nanoparticles (NPs), GA, and GA NPs. Materials and methods The prepared nanoparticle formulations for the tested medications were characterized using Transmission Electron Microscope (TEM) and Fourier-Transform Infrared Spectroscopy (FTIR). 141 human mandibular premolars were selected, and their root canals were prepared. Twenty-one roots were then sectioned into 42 tooth slices. All prepared root canals (n = 120) and teeth slices (n = 42) were divided into six groups according to the intracanal medication used. E. faecalis was inoculated in the samples for 21 days to form biofilms, and then the corresponding medications were applied for 7 days. After medication application, the residual E. faecalis bacteria were assessed using CFU, Q-PCR, and SEM. Additionally, the effect of Ca(OH) 2-GA NPs on E. faecalis biofilm genes (agg, ace, and efaA) was investigated using RT-PCR. Data were statistically analyzed at a 0.05 level of significance. Results The synthesis of NPs was confirmed using TEM. The results of the FTIR proved that the Ca(OH) 2 was successfully encapsulated in the GA NPs. Ca(OH) 2-GA NPs caused a significant reduction in the E. faecalis biofilm gene expression when compared to the control (p < 0.001). There were significant differences in the E. faecalis CFU mean count and CT mean values between the tested groups (p < 0.001) except between the Ca(OH) 2 and GA CFU mean count. Ca(OH) 2-GA NPs showed the least statistical E. faecalis mean count among other groups. SEM observation showed that E. faecalis biofilm was diminished in all treatment groups, especially in the Ca(OH) 2-GA NPS group when compared to the control group. Conclusions Ca(OH) 2 and GA nanoparticles demonstrate superior anti-E. faecalis activity when compared to their conventional counterparts. Ca(OH) 2-GA NPs showed the best antibacterial efficacy in treating E. faecalis biofilm. The tested NP formulations could be considered as promising intracanal medications.
... Gum Arabic (GA), one of the natural polymers, is non-toxic, water-soluble, and vastly used in the stabilization of the food and pharmaceutical industries [23]. Its structure contains charged amine and carboxyl groups that can physically adsorb into the nanoparticle surface when used as a stabilizer [24,25]. ...
Abstract
Background An innovative intracanal medication formulation was introduced in the current study to improve
the calcium hydroxide (Ca(OH)2) therapeutic capability against resistant Enterococcus faecalis (E. faecalis) biofilm.
This in-vitro study aimed to prepare, characterize, and evaluate the antibacterial efficiency of Ca(OH)2 loaded on
Gum Arabic (GA) nanocarrier (Ca(OH)2-GA NPs) and to compare this efficiency with conventional Ca(OH)2, Ca(OH)2
nanoparticles (NPs), GA, and GA NPs.
Materials and methods The prepared nanoparticle formulations for the tested medications were characterized
using Transmission Electron Microscope (TEM) and Fourier-Transform Infrared Spectroscopy (FTIR). 141 human
mandibular premolars were selected, and their root canals were prepared. Twenty-one roots were then sectioned
into 42 tooth slices. All prepared root canals (n=120) and teeth slices (n=42) were divided into six groups according
to the intracanal medication used. E. faecalis was inoculated in the samples for 21 days to form biofilms, and then the
corresponding medications were applied for 7 days. After medication application, the residual E. faecalis bacteria were
assessed using CFU, Q-PCR, and SEM. Additionally, the effect of Ca(OH)2-GA NPs on E. faecalis biofilm genes (agg, ace,
and efaA) was investigated using RT-PCR. Data were statistically analyzed at a 0.05 level of significance.
Results The synthesis of NPs was confirmed using TEM. The results of the FTIR proved that the Ca(OH)2 was
successfully encapsulated in the GA NPs. Ca(OH)2-GA NPs caused a significant reduction in the E. faecalis biofilm gene
expression when compared to the control (p<0.001). There were significant differences in the E. faecalis CFU mean
count and CT mean values between the tested groups (p<0.001) except between the Ca(OH)2 and GA CFU mean
count. Ca(OH)2-GA NPs showed the least statistical E. faecalis mean count among other groups. SEM observation
showed that E. faecalis biofilm was diminished in all treatment groups, especially in the Ca(OH)2-GA NPS group when
compared to the control group.
Conclusions Ca(OH)2 and GA nanoparticles demonstrate superior anti-E. faecalis activity when compared to their
conventional counterparts. Ca(OH)2-GA NPs showed the best antibacterial efficacy in treating E. faecalis biofilm. The
tested NP formulations could be considered as promising intracanal medications.
... Gum Arabic (GA), one of the natural polymers, is non-toxic, water-soluble, and vastly used in the stabilization of the food and pharmaceutical industries [23]. Its structure contains charged amine and carboxyl groups that can physically adsorb into the nanoparticle surface when used as a stabilizer [24,25]. ...
... Gum Arabic (GA), one of the natural polymers, is non-toxic, water-soluble, and vastly used in the stabilization of the food and pharmaceutical industries [23]. Its structure contains charged amine and carboxyl groups that can physically adsorb into the nanoparticle surface when used as a stabilizer [24,25]. ...
Background
An innovative intracanal medication formulation was introduced in the current study to improve the calcium hydroxide (Ca(OH)2) therapeutic capability against resistant Enterococcus faecalis (E. faecalis) biofilm. This in-vitro study aimed to prepare, characterize, and evaluate the antibacterial efficiency of Ca(OH)2 loaded on Gum Arabic (GA) nanocarrier (Ca(OH)2-GA NPs) and to compare this efficiency with conventional Ca(OH)2, Ca(OH)2 nanoparticles (NPs), GA, and GA NPs.
Materials and methods
The prepared nanoparticle formulations for the tested medications were characterized using Transmission Electron Microscope (TEM) and Fourier-Transform Infrared Spectroscopy (FTIR). 141 human mandibular premolars were selected, and their root canals were prepared. Twenty-one roots were then sectioned into 42 tooth slices. All prepared root canals (n = 120) and teeth slices (n = 42) were divided into six groups according to the intracanal medication used. E. faecalis was inoculated in the samples for 21 days to form biofilms, and then the corresponding medications were applied for 7 days. After medication application, the residual E. faecalis bacteria were assessed using CFU, Q-PCR, and SEM. Additionally, the effect of Ca(OH)2-GA NPs on E. faecalis biofilm genes (agg, ace, and efaA) was investigated using RT-PCR. Data were statistically analyzed at a 0.05 level of significance.
Results
The synthesis of NPs was confirmed using TEM. The results of the FTIR proved that the Ca(OH)2 was successfully encapsulated in the GA NPs. Ca(OH)2-GA NPs caused a significant reduction in the E. faecalis biofilm gene expression when compared to the control (p < 0.001). There were significant differences in the E. faecalis CFU mean count and CT mean values between the tested groups (p < 0.001) except between the Ca(OH)2 and GA CFU mean count. Ca(OH)2-GA NPs showed the least statistical E. faecalis mean count among other groups. SEM observation showed that E. faecalis biofilm was diminished in all treatment groups, especially in the Ca(OH)2-GA NPS group when compared to the control group.
Conclusions
Ca(OH)2 and GA nanoparticles demonstrate superior anti-E. faecalis activity when compared to their conventional counterparts. Ca(OH)2-GA NPs showed the best antibacterial efficacy in treating E. faecalis biofilm. The tested NP formulations could be considered as promising intracanal medications.
... Appliance of green chemistry to the synthesis of nanomaterials has an essential value in medicinal and scientific aspects [8,9]. Biologically synthesized silver nanoparticles (AgNPs) have wide range of applications because of their notable physical and chemical properties. ...
The synthesis, characterization and application of biologically synthesized nanomaterials are an important aspect in nanotechnology. The present study deals with the synthesis of silver nanoparticles (AgNPs) using aqueous extract of brown seaweed Dictyota Bartayresiana as the reducing agent. The formation of AgNPs was confirmed by UV-Vis Spectroscopy, Scanning electron microscopy (SEM) and Transmission electron microscopy (TEM). The synthesized AgNPs was predominately crystalline in shape, polydispersed and ranged from 15 to 40 nm in size. Fourier Transform Infra-Red (FT-IR) spectroscopy analysis showed that the synthesized AgNPs was capped with bimolecular compounds which are responsible for reduction of silver ions. The antifungal effects of these AgNPs were studied against Humiclo insulans (MTCC 4520) and Fusarium dimerum (MTCC 6583). The present study indicates that AgNPs has considerable antifungal activity in comparison with other antifungal drugs.
... 73,74 This polymer is widely used as a stabilizer, reducing agent, emulsifying agent, and additive in various NP syntheses. [75][76][77][78] The functional hydroxyl groups in the structure of this natural polymer can make a physicochemical hydrogen bond with hydroxyl groups on the surface of MNPs. 79 Other hydroxyl groups not involved in hydrogen bonds can be functionalized by covalent bonds with various linkers. ...
Triazoles are biologically important compounds that play a crucial role in biomedical applications. In this
study, we present an innovative and eco-friendly nanocatalyst system for synthesizing compounds via
the click reaction. The system is composed of Arabic gum (AG), iron oxide magnetic nanoparticles
(Fe3O4 MNPs), (3-chloropropyl) trimethoxysilane (CPTMS), 2-aminopyridine (AP), and Cu(I) ions. Using AP
as an anchor for Cu(I) ions and Fe3O4 MNPs allows facile separation using an external magnet. The
hydrophilic nature of the Fe3O4@AG/AP-Cu(I) nanocomposite makes it highly efficient in water as
a green solvent. The highest reaction efficiency (95.0%) was achieved in H2O solvent with 50.0 mg of
nanocatalyst for 60 min at room temperature. The reaction yield remained consistent for six runs,
demonstrating the stability and effectiveness of the catalyst.
... Various heavy metal-based NPs have been investigated as potential CT contrast agents, including NPs made of palladium (Pd, Z = 46) [24], silver (Ag, Z = 47) [25][26][27][28], cerium (Ce, Z = 58) [29,30], gadolinium (Gd, Z = 64) [31][32][33][34][35], dysprosium (Dy, Z = 66) [32,36,37], holmium (Ho, Z = 67) [37][38][39][40], ytterbium (Yb, Z = 70) [32,[41][42][43][44][45][46], tantalum (Ta, Z = 73) [32,[47][48][49][50] , tungsten (W, Z = 74) [51][52][53][54][55], platinum (Pt, Z = 78) [56][57][58][59][60][61][62][63], gold (Au, Z = 79) [64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81], and bismuth (Bi, Z = 83) [32,[82][83][84][85][86][87][88]. These NPs are overviewed (Table 1) and their performances are compared with those of commercial iodinebased CT contrast agents based on their X-ray attenuation efficiencies and in vivo performance. ...
Contrast agents developed for X-ray computed tomography (CT) offer extremely valuable tools and techniques in diagnostics via contrast enhancements. Heavy metal-based nanoparticles (NPs) can provide high contrast in CT images. These result from a high density of heavy metal atoms with high X-ray attenuation coefficients that exceed that of iodine (I), which is currently used in hydrophilic organic CT contrast agents. Nontoxicity and colloidal stability are vital characteristics in designing heavy metal-based NPs as CT contrast agents. In addition, the particle size must be small for in vivo renal excretion. In vitro phantom imaging studies can provide X-ray attenuation efficiency, which is a critical parameter for CT contrast agents, and the imaging performance of CT contrast agents can be demonstrated via in vivo experiments. This review focuses on in vitro and in vivo studies of various heavy metal-based NPs (metal: Au, Pt, Pd, Ag, Ce, Gd, Dy, Ho, Yb, Ta, W, and Bi) and provides an outlook on their use as high-performance CT contrast agents.
... Biocompatible gold NPs can be created by continuously mixing an aqueous gum Arabic solution (0.2 percent), phosphine amino acid, and NaAuCl 4 together. The produced NPs can be used as molecular imaging contrast agents and can exhibit in vitro and in vivo endurance for months in aqueous, salt, and buffered solutions using an X-ray computed tomography scan [14]. ...
Recently, there have been various chemical carriers and routines for treatment of infections. Plant gum nanoparticles are being used greatly for this purpose. They have several advantages over chemical drug carriers including being biodegradable, biocompatible, nontoxic, providing better tolerance to the patient, and having fewer side effects. They also do not cause allergies in humans, do not irritate the skin or eyes, and have low production costs. The use of plant gums as drug carriers is limited due to a series of disadvantages. They may have microbial contamination because of the moisture in their content. Also, in storage, their viscosity decreases due to contact with water. By green nanoparticle synthesis of these plant gums as drug carriers, the disadvantages can be limited. There are several studies showing that plant gum drug carriers can have a great combination with various drugs and nanoparticles, thus they could be extremely effective against multi-resistant bacteria and even systemic illness like cancer. These days, the need for green synthesis of medicine and drug carriers has become quite popular and it will be even more essential in the future because of emerging antibiotic-resistant bacteria and climate change.
... AuNPs are inherently biocompatible and exhibit higher drug loading and improved pharmacological response [27]. In the synthesis of AuNPs, countless scientists have found that the physical and chemical character of nanoparticles changes [28,29]. Stabilizing AuNPs with biodegradable polymers and gums is an innovative field of study for synthesizing more suitable nanomaterials. ...
The objective of the study was to develop a transdermal nanoformulation of hesperidin (HSP) against Proteus vulgaris (P. vulgaris). Based on the low water solubility of HSP, we prepared HSP-enabled AuNPs stabilized with xanthan gum (XA), referred to as HSP@XA@AuNPs. The HSP@XA@AuNP formulation was evaluated for particle size (43.16 nm), PDI (0.565), zeta potential (−31.9 mV), and entrapment efficiency (56.7%). The HSP@XA@AuNPs gel was developed by incorporating selected formulation grades into a 1% Carbopol gel base and characterized by physical evaluation and rheological studies. The color of the HSP@XA@AuNP gel was light pink, and the texture was very smooth and non-greasy. The gel was shown to be odorless. A field emission scanning electron microscope (FESEM) was used to investigate the shape of HSP@XA@AuNPs further. The drug release was 73.08% for the HSP@XA@AuNPs and 86.26% for the HSP@XA@AuNPs gel in 500 min. The prepared gel showed antimicrobial activity against P. vulgaris with an MIC of 1.78 μg/mL. In conclusion, the HSP@XA@AuNPs gel could be an advanced modality for treating P. vulgaris.
... For example, magnetite nanoparticles (one of the iron oxides) were encapsulated in Arabic gum to increase the agent's stability [9]. Because gold nanoparticles (AuNPs) are resistant to oxidation, nanoparticles containing AuNP are now depleted due to toxicity [10]. (Figure 3), like Arabic gum, has an ancient history that is a dry exudate from the stems and branches of Astragalus gummifer (and other Asian species of Astragalus (legumes group)) [2]. ...
The unique attributes, biodegradability, biocompatibility, perfect accessibility, and low production costs led to the use of natural gums in a different section of our lives. Among them, we can mention gums obtained from microorganisms (xanthan gum and gellan gum), plant tissues (Arabic gum and gum tragacanth), seeds (konjac gum and guar gum), seaweeds (alginates, agar gum, and carrageenans). Gums have essential applications in the medical and pharmaceutical, food, biotechnology, and critical agricultural industries. Encapsulation is one of the new methods to increase the stability of bioactive compounds during processing and storage. Encapsulation technology using natural gums is a new way to improve the performance of microbial agents in various sciences, especially agriculture, which represents a bright future in this field.
Resveratrol functionalized palladium nanoparticles (Res-PdNPs) inhibit NF-κB, reprogram tumor-associated macrophages from the M2 to the M1 phenotype, and enhance in vivo anti-tumor activity.
Introduction: As the largest organ of the body, the skin is exposed to physical, chemical and biological damage, and skin cancer is one of the most common types of cancer. Due to side effects and drug resistance, the development of herbal medicines using nanotechnology has received much attention.
Materials and methods: In this study, three types of nanofibers were prepared by electrospinning method, and prepared nanofiber were evaluated by SEM and FTIR analyses. Next, the toxicity of these nanofibers was investigated on melanoma cancer cells (A-375) and healthy cells (HFFF2) of human skin.
Results: Polyethylene oxide nanofibers with an average diameter of 9 ± 187 nm, polyethylene oxide-gum arabic nanofibers with an average diameter of 27 ± 200 nm, and polyethylene oxide-gum arabic-menthol with a diameter of 46 ± 338 nm were prepared. The morphology of these nanofibers was investigated with the help of scanning electron microscope. The results showed that polyethylene oxide-gum arabic-menthol nanofibers had the most toxic effect on cancer cells, which is significantly less on healthy skin cells.
Conclusion: Due to the non-toxicity of polyethylene oxide-gum arabic-menthol nanofibers on healthy skin cells, it can be used as a non-toxic wound dressing after complete in-vivo studies.
The term “nanotechnology,” or “nanoscience,” refers to the science carried out on a nanometer scale and alludes to structures having a dimension between 1 and 100 nm. In the last 20 years alone, the nanoneuroscience and nanoneurosurgery fields have emerged as new frontiers of science, leading to astonishing advancements in biomedical science and clinical practice. Nanotechnology emerged as a field of study in the twentieth century with Richard Feynman, Norio Taniguchi, Eric Drexler, and Robert A. Freitas Jr as some of the original visionaries who set a course that would lead to the application of nanomechanical concepts in neurosurgery and nanoneurosurgery. After the discovery of carbon nanoparticles and nanotubes in the late twentieth century, there was a major growth of interest in the application of nanotechnology in material, electrical, and optical engineering. Not long after, a search for applications in biomedical science began, finding uses in drug delivery, nucleic acid/macromolecule delivery, imaging, and as an interface to treat disorders and injuries. Nanomedicine for a neurological or neurosurgical application has not yet been approved by the Food and Drug Administration (FDA); however, a variety of nanoplatforms for biomedical applications are available for research and clinical trials. The continuation of nanotechnology and neuroscience research relies in part on the collaborative efforts of the US Congress. The National Nanotechnology Initiative (NNI) was launched in 2000 by President Clinton to help fund the development of nanotechnologies applicable to neurosurgical uses. The United States Congressional Neuroscience Caucus has a mission to raise awareness of the importance of neuroscience research in the hope of spurring support from society and federal policy.
Recent advancements in nanotechnology have revolutionized medical imaging and therapeutics by introducing a wide range of nanomaterials. These nanoparticles possess exceptional properties such as increased surface area, enhanced optical characteristics, and improved mechanical and magnetic properties. They can be categorized based on their size, shape, and nature. Nanoparticles have exhibited promising results in enhancing the sensitivity of magnetic resonance imaging (MRI), overcoming the limitations of optical imaging techniques, and improving drug delivery through the blood–brain barrier. Specifically, gadolinium (Gd)-based metallofullerenes (MFs) and iron oxide nanoparticles have shown immense potential for MRI, while gold nanoparticles (GNPs) have demonstrated remarkable photothermal properties for therapy. The development of targeted molecular imaging agents and multifunctional nanoprobes has further expanded the scope of their applications. Gadolinium-based endohedral MFs have emerged as particularly noteworthy nanomaterials, offering significant MRI relaxivity properties compared to conventional Gd chelates, with enhancements of up to 20 times (Mikawa, Bioconjugate Chemistry 12: 510–514, 2001) and 30 times (Fatouros, Radiology 240: 756–764, 2006). The relaxivity mechanism of these metallofullerenes differs from that of classical Gd chelates as it relies on the electronic interactions between the fullerene cage and water molecules, instead of internal water interactions.
This unique property enhances water solubility and optimizes the magnetic coupling between Gd3+ unpaired electrons and external water protons. Moreover, the presence of hydroxyl groups on the surface facilitates proton exchange, further expanding their potential applications in tumor treatment and antioxidant activity. Overall, these advancements in nanomaterials hold tremendous promise in revolutionizing medical imaging and therapeutics.
Background: Invasive cervical cancer is recognized as the second most common malignancy in women after breast cancer. Objectives: This study investigates, for the first time, the effect of gold nanoparticle-doped graphene oxide (GO) nanosheets on the human epithelial carcinoma (HeLa) cell line in the presence of heliox cold plasma. Methods: Graphene oxide nanosheets were synthesized using the Hummer method and then doped with gold nanoparticles. The nanoparticles were characterized by transmission electron microscopy (TEM), and the diffraction peaks of GO and gold nanoparticles were confirmed through X-ray diffraction (XRD) analysis. Additionally, the optical absorbance of the nanoparticles was measured in the range of 200 - 900 nm using UV-Visible spectroscopy. A plasma generator was fabricated to produce cold plasma using helium (He) and oxygen (O₂) gases at a 99:1 ratio. The radicals generated by the cold plasma were analyzed via optical emission spectroscopy (OES). Cell treatment was conducted by applying various concentrations of GO and GO/Au nanoparticles. Cellular phenotype was monitored through optical microscopy, and biocompatible concentrations of both nanoparticles were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Subsequently, cold plasma at varying distances and durations was applied to the nanoparticle-treated cells. The generated radicals and the expression of apoptotic genes in treated cells were assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and real-time PCR, respectively. Results: The width of the bacillus-like gold nanoparticles was 15.13 ± 0.96 nm. The cold plasma generated radicals such as N2I2⁺, N2II1⁻, He•, and O⁻•. XRD analysis confirmed the successful coupling of gold onto the GO nanosheets. The biocompatible concentrations of GO and GO/Au nanoparticles were found to be 30 µg/100 µL and 20 µg/100 µL, respectively, as determined by the MTT assay. Radical formation increased as incubation time was extended from 30 to 60 seconds. Furthermore, real-time PCR analysis demonstrated the highest levels of p53, Bax, and caspase 3/8 expression at a plasma exposure time of 60 seconds in the composite-treated group, while Bcl2 expression was significantly reduced. Conclusions: The findings suggest that the parameters of heliox cold plasma and the concentrations of GO/Au nanoparticles must be optimized to effectively induce apoptosis in cervical cancer cells.
Lanthanide-based nanoparticles (Ln-NPs) are highly valued for their unique optical and magnetic properties, making them useful in various scientific fields, including materials science and biomedicine. This study investigated the use...
Purpose
Breast cancer is a significant global health issue, contributing to 15% of cancer-related deaths. Our laboratory has pioneered a novel approach, combining Ayurvedic principles with green nanotechnology, to develop a scientifically rigorous medical modality referred to as Nano-Ayurvedic Medicine, recently approved by the US Patents and Trademarks Office. Here in we report a new Nano-Ayurvedic medicine agent derived from gold nanoparticles encapsulated with phytochemicals from Ginkgo biloba plant (GB-AuNPs).
Methods
We have developed biocompatible gold nanoparticles using electron-rich phytochemicals from Ginkgo biloba as reducing agent cocktail. Ginkgo biloba phytochemical-encapsulated gold nanoparticles (GB-AuNPs) were fully characterized, and their anticancer activity, including immunomodulatory profiles, were evaluated against breast (MDAMB-231) cancer cell lines.
Results
Characterization revealed spherical morphology for GB-AuNPs and possessed optimum in vitro stability through high zeta potential of −34 mV for optimum in vivo stability. The core size of GB-AuNPs of 19 nm allows for penetration into tumor cells through both EPR effects as well as through the receptor-mediated endocytosis. The Antitumor efficacy of this nano-ayurvedic medicine agent revealed strong antitumor effects of GB-AuNPs towards MDAMB-231. Our investigations reveal that GB-AuNPs enhance anti-tumor cytokines (IL-12, TNF-α, IFN-γ) and reduce pro-tumor cytokines (IL-10, IL-6), promoting the conversion of protumor M2 macrophages into M1-like macrophage antitumor phenotype. Cellular studies show that GB-AuNPs offer superior anti-tumor efficacy and a better safety profile against breast tumors compared to cisplatin.
Conclusion
Our investigations have demonstrated that the nano-ayurvedic medicine agent, GB-AuNPs, treats cancers through an immunomodulatory mechanism facilitated by elevated levels of anti-tumor cytokines (TNF-α, IFN-γ and IL-12) with concomitant downregulation of pro-tumor cytokines expression (IL-6 and IL-10). The green nanotechnology approach for the development of nano-ayurvedic medicine agent (GB-AuNPs), as described in this paper, presents new and attractive opportunities for treating human cancers and other debilitating diseases and disorders.
Nanocomposite materials are emerging as key players in addressing critical challenges in healthcare, energy storage, and environmental remediation. These innovative systems hold great promise in engineering effective solutions for complex problems. Nanocomposites have demonstrated various advantages such as simplicity, versatility, lightweight, and potential cost‐effectiveness. By reinforcing synthetic and natural polymers with nanomaterials, a range of nanocomposites have exhibited unique physicochemical properties, biocompatibility, and biodegradability. Current research on nanocomposites has demonstrated promising clinical and translational applications. Over the past decade, the production of nanocomposites has emerged as a critical nano‐structuring methodology due to their adaptability and controllable surface structure. This comprehensive review article systematically addresses two principal domains. A comprehensive survey of metallic and nonmetallic nanomaterials (nanofillers), elucidating their efficacy as reinforcing agents in polymeric matrices. Emphasis is placed on the methodical design and engineering principles governing the development of functional nanocomposites. Additionally, the review provides an exhaustive examination of recent noteworthy advancements in industrial, environmental, biomedical, and clinical applications within the realms of nanocomposite materials. Finally, the review concludes by highlighting the ongoing challenges facing nanocomposites in a wide range of applications.
Biofilm formation is one of the most vital risk factors for antimicrobial resistance in bacteria. In the present study we investigated the effect of bovine serum albumin-gold nanoclusters (BSA-GNCs) against antibiotic-resistant bacterial susceptibility. BSA-GNCs was synthesized by adding HAuCl 4 and BSA as a capping agent. BSA-GNCs were characterized by UV-Visible spectrophotometer, FTIR, Zeta sizer, SEM-EDX and TEM analysis. Antibacterial activity from antibiotic-resistant bacterial strains Klebsiella pneumoniae, Streptococcus aureus , and non-resistant bacterial strains Pseudomonas aeruginosa and Enterococcus faecalis were assessed using the disc diffusion method. The pellets of the control and BSA-GNCs treated bacteria were procured for transmission electron microscopy. The ultrastructural images of the bacteria were captured using a bottom mounted 15-megapixel Quemesa camera with iTEM software. A peak at λmax = 550nm from UV-Visible spectrophotometer spectrum was confirmed the formation of gold nanoclusters. FTIR peaks were found at 598.33, 1102.79, 1261.21, 1637.84, 2923.54 & 3430.76cm − 1 , and average hydrodynamic particle size distribution peaks were 22.72nm. BSA-GNCs were homogenous as well as cluster nature. BSA-GNC (20µL/disc) treatment inhibited the growth zone of the bacteria ( KP 13.17 ± 1.32, SA 16.67 ± 1.46, PA 23.17 ± 1.82 and EF 25.67 ± 1.93 mm) at 24 hours. The BSA-GNCs treated bacteria accommodating shrunken, stranded and degenerated cytoplasm. The degeneration of the bacteria was more severe in antibiotic susceptible bacteria than antibiotic resistant bacteria. BSA-GNCs attenuate the transport of essential elements to the bacteria leading to the degeneration of the cytoplasm followed by the disintegration of the plasma membrane, cell walls and extinguishing the bacteria.
The utilization of engineered gold nanoparticles (GNPs) in biomedical applications is experiencing rapid growth owing to their reactive nature and remarkable flexibility. However, despite these advantages, concerns persist regarding their in vivo biocompatibility and cytotoxicity. This study aimed to assess the toxicity, biodistribution, and excretion pathways of GNPs functionalized with various antibiotics, namely, ciprofloxacin, levofloxacin, cefotaxime, and ceftriaxone, using a mouse model. Following intravenous administration, the nanostructures induced an increase in serum enzyme levels and histological abnormalities in the liver, indicating potential hepatotoxic effects. Analysis of organ distribution revealed accumulation primarily in the liver and spleen, with concentrations gradually decreasing 168-h post-administration. Fecal excretion was identified as the primary route of elimination, with a smaller portion excreted via urine. Among the different nanostructures evaluated, those functionalized with levofloxacin (LEV-NP) exhibited minimal organ toxicity and a high clearance rate. Additionally, LEV-NP, with a size of approximately 12 nm, demonstrated superior drug particle stability and lower red blood cell hemolytic activity compared to other nanostructures.
We describe the use of biocompatible gum acacia (GA)-assembled Ag-TiO2 and Ag-SiO2 nanostructures as effective heterogeneous catalysts for the synthesis of 5-substituted 1H-tetrazoles through the traditional [3+2] cycloaddition of aryl nitriles with sodium azides. Characterization of the prepared catalysts employing TEM, XPS, FE-SEM, FT-IR, XRD, and TGA-DTG reveals silver nanoparticles encapsulated in the GA matrix amidst modified nano titania or silica. A variety of structurally divergent aryl nitriles were converted into the corresponding tetrazoles in a short reaction time. Other advantages include low catalytic load, easy handling of catalyst, limited use of toxic reagents, and desirable conversion yields, making this protocol a viable and practical alternative for this cyclization. The catalysts can be easily recovered and reused over multiple cycles without significant loss of catalytic activity.
X-ray computed tomography (CT) contrast agents offer extremely valuable tools and techniques in diagnostics via contrast enhancements. Heavy metal-based nanoparticles (NPs) can provide high contrast in CT images due to the high density of heavy metal atoms with high X-ray attenuation coefficients that exceed that of iodine (I), which is currently used in hydrophilic organic CT contrast agents. Nontoxicity and colloidal stability are vital characteristics in designing heavy metal-based NPs as CT contrast agents. In addition, a small particle size is desirable for in vivo renal excretion. In vitro phantom imaging studies have been performed to obtain X-ray attenuation efficiency, which is a critical parameter for CT contrast agents, and the imaging performance of CT contrast agents has been demonstrated via in vivo experiments. In this review, we focus on the in vitro and in vivo studies of various heavy metal-based NPs in pure metallic or chemical forms, including Au, Pt, Pd, Ag, Ce, Gd, Dy, Ho, Yb, Ta, W, and Bi, and provide an outlook on their use as high-performance CT contrast agents.
NDBs were fabricated from gum Arabic (GA) and polyvinyl alcohol (PVA) in different ratios using novel techniques (casting, dehydration, and peeling). The GA/PVA blends were cast with a novel vibration-free horizontal flow (VFHF) technique, producing membranes free of air bubble defects with a homogenous texture, smooth surface, and constant thickness. The casting process was achieved on a self-electrostatic template (SET) made of poly-(methyl methacrylate), which made peeling the final product membranes easy due to its non-stick behavior. After settling the casting of the membranous, while blind, the sheets were dried using nanometric dehydration under a mild vacuum stream using a novel stratified nano-dehydrator (SND) loaded with P2O5. After drying the NDB, the dry, smooth membranes were peeled easily without scratching defects. The physicochemical properties of the NDBs were investigated using FTIR, XRD, TGA, DTA, and AFM to ensure that the novel techniques did not distort the product quality. The NDBs retained their virgin characteristics, namely, their chemical functional groups (FTIR results), crystallinity index (XRD data), thermal stability (TGA and DTA), and ultrastructural features (surface roughness and permeability), as well as their microbial biodegradation ability. Adding PVA enhanced the membrane’s properties except for mass loss, whereby increasing the GA allocation in the NDB blend reduces its mass loss at elevated temperatures. The produced bioplastic membranes showed suitable mechanical properties for food packaging applications and in the pharmaceutical industry for the controlled release of drugs. In comparison to control samples, the separated bacteria and fungi destroyed the bioplastic membranes. Pseudomonas spp. and Bacillus spp. were the two main strains of isolated bacteria, and Rhizobus spp. was the main fungus. The nano-dehydration method gave the best solution for the prompt drying of water-based biopolymers free of manufacturing defects, with simple and easily acquired machinery required for the casting and peeling tasks, in addition to its wonderful biodegradation behavior when buried in wet soil.
Objective:
This study aims to investigate the acute and chronic adverse effects of ∼50 nm (nanometer) gold nanoparticles (AuNPs) synthesized using Ziziphus zizyphus leaf extract in mice.
Significance:
AuNPs have shown promise for medical applications, but their safety and biocompatibility need to be addressed. Understanding the potential adverse effects of AuNPs is crucial to ensure their safe use in medical applications.
Methods:
The ∼50 nm AuNPs were synthesized using Ziziphus zizyphus leaf extract and characterized using scanning electron microscopy, dynamic light scattering, and zeta potential analysis. Mice were subjected to a single intraperitoneal injection of AuNPs at a dose of 1 g/mg (grams per milligram) or a daily dose of 1 mg/kg for 28 days. Various parameters, including gold bioaccumulation, survival, behavior, body weight, and blood glucose levels, were measured. Histopathological changes and organ indices were assessed.
Results:
Gold levels in the blood and heart did not significantly increase with daily administration of AuNPs. However, there were proportional increases in gold content observed in the liver, spleen, and kidney, indicating effective tissue uptake. Histopathological alterations were predominantly observed in the kidney, suggesting potential tissue injury.
Conclusions:
The findings of this study indicate that ∼50 nm AuNPs synthesized using Z. zizyphus leaf extract can induce adverse effects, particularly in the kidney, in mice. These results highlight the importance of addressing safety concerns when using AuNPs in medical applications. Further investigations that encompass a comprehensive set of toxicological parameters are necessary to confirm the long-term adverse effects of AuNP exposure.
NDBs were fabricated from gum arabic (GA) and polyvinyl alcohol (PVA) in different ratios using novel techniques (casting, dehydration, and peeling). The GA/PVA blends were cast with a novel vibration-free horizontal flow (VFHF) technique, producing membranes free of air bubble defects with a homogenous texture, smooth surface, and constant thickness. The casting process was achieved on a self-electrostatic template (SET) made of poly-(methyl methacrylate), which made peeling the final product membranes easy due to its non-stick behavior. After settling of the cast membranous blind, sheets were dried using nanometric dehydration under a mild vacuum stream using a novel stratified nanodehydrator (SND) loaded with P2O5. After drying the TBM, the dry, smooth membranes were peeled easily without scratching defects. The physicochemical properties of the NDBs were investigated using FTIR, XRD, TGA, DTA, and AFM to ensure that the novel techniques did not distort the product quality. The NDBs retained their virgin characteristics, namely, their chemical functional groups (FTIR results), crystallinity index (XRD data), thermal stability (TGA and DTA), and ultrastructural features (surface roughness and permeability), as well as their microbial biodegradation ability. Comparing the two TBM’ s precursors, PVA had a higher crystallinity index (CI), more mass loss at higher temperatures, greater thermal stability due to higher heat resistance, and a higher clearance of surface roughness due to its large particle size (PS), as well as its higher permeability parameters, namely pore diameter (PD) and void volume (VV), than those for GA. Accordingly, increasing the PVA allocation in the bioplastic blends can enhance their properties except for mass loss, whereby increasing the GA allocation in the TBM blend reduces its mass loss at an elevated temperature. In addition, there is no statistical difference between the NDBs and ordinary air-dried NDBs in PS, PD, and VV, indicating that the novel procedures used did not distort their parent properties examined, as well as their ability for biodegradation. In comparison to control samples, the separated bacteria and fungus destroyed the NDBs. Pseudomonas spp. and Bacillus spp. were the two main strains of isolated bacteria, and Rhizobus spp. was the main fungus. The nanodehydration method gave the best solution for the prompt drying of water-based biopolymers free of manufacturing defects, with simple and easily acquired machinery required for the casting and peeling tasks, in addition to its wonderful biodegradation behavior when buried in wetted soil.
The study attempted to use systematic and thematic analysis of reported top 100 cited articles on Gum research. We adopted systematic and thematic analysis using bibliometric analysis tools, such as Scopus database to search relevant documents in Gum. Data were analyzed by RStudio and VOSviewer, and the top 100 cited articles were systematically classified into structural (both chemical and physical), biological, pharmaceutical, food, and cosmetic properties of Gum. The citation times for the 100 top-cited articles ranged from 93 to 457, with an average citation per document of 151.5 scores. The 100 top-cited articles were published in 48 journals, and the journal "Food hydrocolloids" was a top-rank journal with (n = 15) articles followed by "Carbohydrate polymers" (n = 11) articles. Mcclements DJ was the most productive author (6 articles). China the, USA, and India are the most productive countries with more than 30 articles published in Gum. Among 153 contributed affiliations, King Saud University, Saudi Arabia, and Universiti Putra Malaysia, Malaysia were top affiliations in Gum research with more than 14 published articles. The comprehensive analysis shows that about 78% of articles were focused on the structural, chemical and physical properties (9%) of food biological (8%), and on pharmaceutical properties (5%). This is the first bibliometric analysis to provide a historical perspective on Gum scientific research. The systematic and thematic analysis provides comprehensive information on the scientific research direction , hot topics and trends in Gum.
The present work approaches the production of AuNPs through femtosecond laser ablation of a solid in a liquid media. Aiming at oncological applications, the stabilization of the colloidal solution was performed with non-cytotoxic material.
Gold nanoparticles (GNP) are noble metal nanocarriers that have been recently researched upon for pharmaceutical applications, imaging, and diagnosis. These metallic nanocarriers are easy to synthesize using chemical reduction techniques as their surface can be easily modified. Also, the properties of GNP are significantly affected by its size and shape which mandates its stabilization using suitable techniques of surface modification. Over the past decade, research has focused on surface modification of GNP and its stabilization using polymers, polysaccharides, proteins, dendrimers, and phase-stabilizers like gel phase or ionic liquid phase. The use of GNP for pharmaceutical applications requires its surface modification using biocompatible and inert surface modifiers. The stabilizers used, interact with the surface of GNP to provide either electrostatic stabilization or steric stabilization. This review extensively discusses the surface modification techniques for GNP and the related molecular level interactions involved in the same. The influence of various factors like the concentration of stabilizers used their characteristics like chain length and thickness, pH of the surrounding media, etc., on the surface of GNP and resulting to stability have been discussed in detail. Further, this review highlights the recent applications of surface-modified GNP in the management of tumor microenvironment and cancer therapy.
Laser ablation synthesis in liquid solution (PLAL) is a green technique that allows for the physical formation of nanomaterials. This study indicates the preparation of stable gold nanoparticles (AuNPs) in Gum Arabic (GA) solution via laser ablation as a CT contrast agent. The optical properties were achieved using the absorption spectroscopic technique whereas the morphology and size distribution were investigated by TEM and ImageJ software. TEM image shows greater stability and spherical shape of GA-AuNPs with smaller size at 1.85 ± 0.99 nm compared to AuNPs without GA. The absorption spectrum of pure AuNPs has a lower absorption peak height in the visible range at λ = 521 nm, while the spectrum of GA-AuNPs has a higher plasmon peak height at λ = 514 nm with a blue shift towards lower wavelengths. The concentration of GA that dissolved in 10 mL of DI water via laser ablation is set at 20 mg. Increasing the number of pulses has only a minor effect on particle size distribution, which remains tiny in the nanometer range (less than 3 nm). For energies greater than 200 mJ, there is a blue shift toward shorter wavelengths. As the concentration of GA-AuNPs increases, the CT number is also increased indicating good image contrast. It can be concluded that there is a positive and significant influence of GA as a reducing agent for AuNPs, and a contrast agent for CT imaging which highlights its superiority in future medical applications.
Transition metal and metal oxide nanoparticles have received considerable attention due to their fascinating and promising biological, energy, environmental, and catalytic applications. Different strategies such as physical, chemical, and biological approaches are used to synthesize the nanoparticles into the desired shape, size, and high surface area. However, the physical and chemical approaches have doubts in terms of energy, cost, safety, and environmental concerns. The use of the green approach is now considered simple, cost-effective, environmentally friendly, and renewable using plant and microbe extracts as reducing and stabilizing agents. Phytochemicals in plant extracts and enzymes, coenzymes, proteins, etc. of microorganisms are responsible for the transformation of metal ions into nanoparticles. Therefore, the present review highlights the green synthesis of metal and metal oxide nanoparticles, plausible reaction mechanisms, and the role of the biomolecules in the synthesis. Challenges associated with green synthesis methods are discussed.
Breast cancer is the most common malignancy in women and is rated among one of the three common malignancies worldwide in combination with colon and lung cancer. The escalating mortality rate of breast cancer patients has captivated the attention of the present-day researchers to come up with new management options. According to WHO, early detection, timely diagnosis and comprehensive breast cancer management are the three cornerstones for controlling breast cancer incidences per year. Multidisciplinary theragnostic approaches for simultaneous diagnosis and treatment of breast cancer have further enriched the therapeutic arsenal. Imaging and biopsy play a significant role in the diagnosis of breast cancer. The treatment plan mostly initiates with general surgery or radiation therapy followed up with adjuvant and/or neoadjuvant therapy. Conventional chemotherapeutics in breast cancer suffer from toxicity and lack of site specificity. Bio-safe gold nanoparticles hold sufficient promise for bridging this gap. Diverse phytochemicals-based synthesis routes to arrive at nano-dimensional gold with spotlight on reaction mechanisms, reaction variables, specific advantages, toxicity and their influence in breast cancer conditions are the focus of this work. This review marks the first attempt to explore the potential of phytochemical-derived nano-gold in breast cancer treatment.
Nanotechnology is a progressing and novel technique in healthcare and smart drug delivery. There are many benefits and future aspects of nanogel containing nanoparticles in the advanced diagnosis, mitigation, and treatment of many important disorders with improved outcomes because of its particle size, high stability, biodegradability, biocompatibility, large surface area, and high drug charging capacity. Their small particle size provides the feature basis for drug charging capacity and for the swelling property to form a 3D structure with advantages, limitations, and classification of nanogels. The motive of the review article is to summarise the natural polymers such as Okra gum, Chitosan, Acacia gum, Pullulan, PLA, and PLGA that are employed to prepare nanogels comprising nanoparticles by the chemical crosslinking method. The various applications of these nanogels as nanoparticles in the many fields of healthcare, including local anesthetics, neurodegenerative, anti-inflammatory, vaccine delivery, transdermal delivery, ophthalmology, and diabetes. In this present review article, the author has focused on current trends of nanogel in nanomedicine, oilfield applications, food packing, cancer research, cosmeceutical, and biomedical applications.
A review with refs. on the scientific developments from biol. research that have profoundly changed a no. of concepts in skin physiol. and physiopathol. as applied to skin cosmetics. These developments include studies into new active ingredients as well as new sources of natural active ingredients, knowledge of skin biochem. mechanisms, and knowledge of the way cosmetically functional substances work. [on SciFinder(R)]
We present surface-enhanced Raman scattering (SERS) studies of DNA nucleosides using biologically benign agarose-stabilized gold nanoparticles (AAuNP). We compare the SERS activity of nucleosides with AAuNP to that of commercially obtained citrate-stabilized gold nanoparticles and find the SERS activity to be an order of magnitude higher with AAuNP. The higher SERS activity is explained in terms of the agarose matrix, which provides pathways for the gold nanoparticles to have distinct arrangements that result in stronger internal plasmon resonances.
Dendrimer nanocomposites (DNC) are hybrid nanoparticles formed by the dispersion and immobilization of guest atoms or small clusters in dendritic polymer matrices. They have a great potential in biomedical applications due to their controlled composition, predetermined size, shape and variable surface functionalities. In this work, d =5–25 nm spherical nanoparticles composed of gold and poly(amidoamine) (PAMAM) dendrimers have been selected to demonstrate this nanoparticle based concept. {Au(0) n -PAMAM} gold dendrimer nanocomposites with a well-defined size were synthesized and imaged by transmission electron microscopy both in vitro and in vivo. DNC have also the potential to be used for imaging and drug delivery vehicles either by utilizing bioactive guests or through the incorporation of radioactive isotopes, such as Au-198. Peer Reviewed http://deepblue.lib.umich.edu/bitstream/2027.42/43295/1/11051_2004_Article_5101884.pdf
This investigation was designed to determine whether liver tumor growth can be prevented by localized radioactivity through radioactive gold ( 198Au) infusion. Colloidal 198Au is phagocytosed by Kupffer cells and emits β- and α-radiation. Measurement of α-radiation showed marked 198Au liver concentration. Liver chemistries, histology, and isolated hepatocyte function studies that measure [ 14C]acetate incorporation into bile acid and cholesterol formation after doses from 200 to 3000 μCi were serially determined. A 400-μCi dose (2944 rads) provided substantial local radiation in the liver for 9 days without toxicity. Three hundred twenty-seven male 150-g-Sprague-Dawley rats received either stable ('cold') colloidal gold, 198Au, intraportally or through a peripheral vein within 10 min following intraportal infusion of 10,000,000 Walker 256 sarcoma cells. In 66 other rats intraportal 198Au administration was delayed for 2 weeks after tumor implantation. In rat livers that received 198Au early following tumor injection, significantly fewer tumors were observed than in controls (p < 10 -9). When radiation was delayed for 2 weeks after tumor infusion, the differences were not as significant. Intraportal or systemic 198Au given within 10 min following tumor infusion can protect an animal from hepatic tumor growth without significant liver toxicity. That hepatic radiation may prevent tumor growth may have important clinical implications.
Contrast-detail curves were constructed for liver computed tomographic (CT) images using an objective method. Stimuli were created by superimposing disks at specified locations on sets of 92 normal liver CT images. Bright and dark disks of 9 sizes and 36 possible image contrasts were used. Sets of 92 stimuli were rendered on film at five window widths (64, 128, 256, 512, and 1024 HU). The contrast-detail (CD) curve flattened substantially for disks larger than 7-mm diameter, and its slope (on a log-log plot) was less than predicted from signal-detection theory. Manipulation of display window manipulation had little impact on this disks' visibility. The results indicate that human observers have difficulty visualizing large, low-contrast details on liver CT scans, and suggest that narrowing the display window will have little effect on this limitation.
Recent advances in gold technology have led to probes with improved properties and performance for cell biologists: higher labeling density, better sensitivity, and greater penetration into tissues. Gold clusters, such as the 1.4-nm Nanogold, are gold compounds that can be covalently linked to Fab' antibody fragments, making small and stable probes. Silver enhancement then makes these small gold particles easily visible by EM, LM, and directly by eye. Another advance is the combination of fluorescent and gold probes for correlative microscopy. Chemical crosslinking of gold particles to many biologically active molecules has made possible many novel probes, such as gold-lipids, gold-Ni-NTA, and gold-ATP.
Objectives:
To estimate the short-term benefit and risk of side-effects of injectable gold for rheumatoid arthritis.
Search strategy:
We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to July 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles.
Selection criteria:
Randomized clinical trials (RCT) comparing injectable gold against placebo in patients with rheumatoid arthritis were included.
Data collection and analysis:
Methodological quality of the RCTs was asessed by two reviewers (MS, BS) (kappa=1.0). Rheumatoid arthritis outcome measures were extracted by two reviewers from the publications for the 6 month endpoint. Sufficient data was obtained to conduct a pooled analysis of the number of swollen joints, physician global assessment, patient global assessment and erythrocyte sedimentation rate (ESR). Results were analyzed as standardized weighted mean differences for swollen joints and global assessments and weighted mean differences for ESR. Toxicity was evaluated with pooled odds ratios for withdrawals. Heterogeneity was estimated using a chi-square test. Fixed effects models were used throughout.
Main results:
Four trials and 415 patients were included. A statistically significant benefit was observed for injectable gold when compared to placebo. The standardized weighted difference (effect size) between gold and placebo for the number of swollen joints was -0.5, translating into a percentage change of 30% in favour of gold adjusted for placebo. Statistically significant differences were also observed for ESR and patient and physician assessments. Twenty two percent of the treated patients withdrew from toxicity compared to 4% of controls (OR=3.9 - 95%Cl: 2.1 - 7.2).
Reviewer's conclusions:
Although its use can be limited by the incidence of serious toxicity, injectable gold has an important clinically and statistically significant benefit in the short term treatment of patients with rheumatoid arthritis.
Metal nanoshells are a class of nanoparticles with tunable optical resonances. In this article, an application of this technology to thermal ablative therapy for cancer is described. By tuning the nanoshells to strongly absorb light in the near infrared, where optical transmission through tissue is optimal, a distribution of nanoshells at depth in tissue can be used to deliver a therapeutic dose of heat by using moderately low exposures of extracorporeally applied near-infrared (NIR) light. Human breast carcinoma cells incubated with nanoshells in vitro were found to have undergone photothermally induced morbidity on exposure to NIR light (820 nm, 35 W/cm2), as determined by using a fluorescent viability stain. Cells without nanoshells displayed no loss in viability after the same periods and conditions of NIR illumination. Likewise, in vivo studies under magnetic resonance guidance revealed that exposure to low doses of NIR light (820 nm, 4 W/cm2) in solid tumors treated with metal nanoshells reached average maximum temperatures capable of inducing irreversible tissue damage (DeltaT = 37.4 +/- 6.6 degrees C) within 4-6 min. Controls treated without nanoshells demonstrated significantly lower average temperatures on exposure to NIR light (DeltaT < 10 degrees C). These findings demonstrated good correlation with histological findings. Tissues heated above the thermal damage threshold displayed coagulation, cell shrinkage, and loss of nuclear staining, which are indicators of irreversible thermal damage. Control tissues appeared undamaged.
Progress toward a molecular characterization of cancer would have important clinical benefits; thus, there is an important need to image the molecular features of cancer in vivo. In this paper, we describe a comprehensive strategy to develop inexpensive, rugged and portable optical imaging systems for molecular imaging of cancer, which couples the development of optically active contrast agents with advances in functional genomics of cancer. We describe initial results obtained using optically active contrast agents to image the expression of three well known molecular signatures of neoplasia: including over expression of the epidermal growth factor receptor (EGFR), matrix metallo-proteases (MMPs), and oncoproteins associated with human papillomavirus (HPV) infection. At the same time, we are developing inexpensive, portable optical systems to image the morphologic and molecular signatures of neoplasia noninvasively in real time. These real-time, portable, inexpensive systems can provide tools to characterize the molecular features of cancer in vivo.
Highly sensitive sensor arrays are in high demand for prospective applications in remote sensing and imaging. Measuring microscopic deflections of compliant micromembranes and cantilevers is developing into one of the most versatile approaches for thermal, acoustic and chemical sensing. Here, we report on an innovative fabrication of compliant nanocomposite membranes with nanoscale thickness showing extraordinary sensitivity and dynamic range, which makes them candidates for a new generation of membrane-based sensor arrays. These nanomembranes with a thickness of 25-70 nm, which can be freely suspended over large (hundred micrometres) openings are fabricated with molecular precision by time-efficient, spin-assisted layer-by-layer assembly. They are designed as multilayered molecular composites made of a combination of polymeric monolayers and a metal nanoparticle intralayer. We demonstrate that these nanocomposite membranes possess unparalleled sensitivity and a unique autorecovering ability. The membrane nanostructure that is responsible for these outstanding properties combines multilayered polymer/nanoparticle organization, high polymer-chain orientation, and a pre-stretched state.
A multidimensional image navigation and display software was designed for display and interpretation of large sets of multidimensional and multimodality images such as combined PET-CT studies. The software is developed in Objective-C on a Macintosh platform under the MacOS X operating system using the GNUstep development environment. It also benefits from the extremely fast and optimized 3D graphic capabilities of the OpenGL graphic standard widely used for computer games optimized for taking advantage of any hardware graphic accelerator boards available. In the design of the software special attention was given to adapt the user interface to the specific and complex tasks of navigating through large sets of image data. An interactive jog-wheel device widely used in the video and movie industry was implemented to allow users to navigate in the different dimensions of an image set much faster than with a traditional mouse or on-screen cursors and sliders. The program can easily be adapted for very specific tasks that require a limited number of functions, by adding and removing tools from the program's toolbar and avoiding an overwhelming number of unnecessary tools and functions. The processing and image rendering tools of the software are based on the open-source libraries ITK and VTK. This ensures that all new developments in image processing that could emerge from other academic institutions using these libraries can be directly ported to the OsiriX program. OsiriX is provided free of charge under the GNU open-source licensing agreement at http://homepage.mac.com/rossetantoine/osirix.
Building on the success of organic electronic devices, such as light-emitting diodes and field-effect transistors, procedures for fabricating non-volatile organic memory devices are now being explored. Here, we demonstrate a novel organic memory device fabricated by solution processing. Programmable electrical bistability was observed in a device made from a polystyrene film containing gold nanoparticles and 8-hydroxyquinoline sandwiched between two metal electrodes. The as-prepared device, which is in a low-conductivity state, displays an abrupt transition to a high-conductivity state under an external bias of 2.8 V. These two states differ in conductivity by about four orders of magnitude. Applying a negative bias of 1.8 V causes the device to return to the low-conductivity state. The electronic transition is attributed to the electric-field-induced charge transfer between the gold nanoparticles and 8-hydroxyquinoline. The transition from the low- to the high-conductivity state takes place in nanoseconds, and is non-volatile, indicating that the device may be used for low-cost, high-density memory storage.
Microfluidic laboratory-on-a-chip (LOC) systems based on a modular architecture are presented. The architecture is conceptualized on two levels: a single-chip level and a multiple-chip module (MCM) system level. At the individual chip level, a multilayer approach segregates components belonging to two fundamental categories: passive fluidic components (channels and reaction chambers) and active electromechanical control structures (sensors and actuators). This distinction is explicitly made to simplify the development process and minimize cost. Components belonging to these two categories are built separately on different physical layers and can communicate fluidically via cross-layer interconnects. The chip that hosts the electromechanical control structures is called the microfluidic breadboard (FBB). A single LOC module is constructed by attaching a chip comprised of a custom arrangement of fluid routing channels and reactors (passive chip) to the FBB. Many different LOC functions can be achieved by using different passive chips on an FBB with a standard resource configuration. Multiple modules can be interconnected to form a larger LOC system (MCM level). We demonstrated the utility of this architecture by developing systems for two separate biochemical applications: one for detection of protein markers of cancer and another for detection of metal ions. In the first case, free prostate-specific antigen was detected at 500 aM concentration by using a nanoparticle-based bio-bar-code protocol on a parallel MCM system. In the second case, we used a DNAzyme-based biosensor to identify the presence of Pb²⁺ (lead) at a sensitivity of 500 nM in <1 nl of solution.
• laboratory-on-a-chip
• microfluidic breadboard
• polydimethylsiloxane
Gold nanorods excited at 830 nm on a far-field laser-scanning microscope produced strong two-photon luminescence (TPL) intensities, with a cos⁴ dependence on the incident polarization. The TPL excitation spectrum can be superimposed onto the longitudinal plasmon band, indicating a plasmon-enhanced two-photon absorption cross section. The TPL signal from a single nanorod is 58 times that of the two-photon fluorescence signal from a single rhodamine molecule. The application of gold nanorods as TPL imaging agents is demonstrated by in vivo imaging of single nanorods flowing in mouse ear blood vessels.
• in vivo imaging
• plasmon resonance
• multiphoton
• nonlinear optics
The goal of this study was to determine if an iodinated, liposomal contrast agent could be used for high-resolution, micro-CT of low-contrast, small-size vessels in a murine model.
A second-generation, liposomal blood pool contrast agent encapsulating a high concentration of iodine (83-105 mg I/mL) was evaluated. A total of five mice weighing between 20 and 28 g were infused with equivalent volume doses (500 microL of contrast agent/25 g of mouse weight) and imaged with our micro-CT system for intervals of up to 240 min postinfusion. The animals were anesthetized, mechanically ventilated, and vital signs monitored allowing for simultaneous cardiac and respiratory gating of image acquisition.
Initial enhancement of about 900 H in the aorta was obtained, which decreased to a plateau level of approximately 800 H after 2 hr. Excellent contrast discrimination was shown between the myocardium and cardiac blood pool (650-700 H). No significant nephrogram was identified, indicating the absence of renal clearance of the agent.
The liposomal-based iodinated contrast agent shows long residence time in the blood pool, very high attenuation within submillimeter vessels, and no significant renal clearance rendering it an effective contrast agent for murine vascular imaging using a micro-CT scanner.
Noble-metal nanoparticles embedded in dielectric matrices are considered to have practical applications in ultrafast all-optical switching devices owing to their enhanced third-order nonlinear susceptibility, especially near the surface-plasmon-resonance (SPR) frequency. Here we present the use of a microreactor approach to the fabrication of a self-organized photosensitive gold nanoparticle chain encapsulated in a dielectric nanowire. Such a hybrid nanowire shows pronounced SPR absorption. More remarkably, a strong wavelength-dependent and reversible photoresponse has been demonstrated in a two-terminal device using an ensemble of gold nanopeapodded silica nanowires under light illumination, whereas no photoresponse was observed for the plain silica nanowires. These results show the potential of using gold nanopeapodded silica nanowires as wavelength-controlled optical nanoswitches. The microreactor approach can be applied to the preparation of a range of hybrid metal-dielectric one-dimensional nanostructures that can be used as functional building blocks for nanoscale waveguiding devices, sensors and optoelectronics.
Nanomaterials have become increasingly important in the development of new molecular probes for in vivo imaging, both experimentally and clinically. Nanoparticulate imaging probes have included semiconductor quantum dots, magnetic and magnetofluorescent nanoparticles, gold nanoparticles and nanoshells, among others. However, the use of nanomaterials for one of the most common imaging techniques, computed tomography (CT), has remained unexplored. Current CT contrast agents are based on small iodinated molecules. They are effective in absorbing X-rays, but non-specific distribution and rapid pharmacokinetics have rather limited their microvascular and targeting performance. Here we propose the use of a polymer-coated Bi(2)S(3) nanoparticle preparation as an injectable CT imaging agent. This preparation demonstrates excellent stability at high concentrations (0.25 M Bi(3+)), high X-ray absorption (fivefold better than iodine), very long circulation times (>2 h) in vivo and an efficacy/safety profile comparable to or better than iodinated imaging agents. We show the utility of these polymer-coated Bi(2)S(3) nanoparticles for enhanced in vivo imaging of the vasculature, the liver and lymph nodes in mice. These nanoparticles and their bioconjugates are expected to become an important adjunct to in vivo imaging of molecular targets and pathological conditions.
There have been few fundamental improvements in clinical X-ray contrast agents in more than 25 years, and the chemical platform of tri-iodobenzene has not changed. Current agents impose serious limitations on medical imaging: short imaging times, the need for catheterization in many cases, occasional renal toxicity, and poor contrast in large patients. This report is the first demonstration that gold nanoparticles may overcome these limitations. Gold has higher absorption than iodine with less bone and tissue interference achieving better contrast with lower X-ray dose. Nanoparticles clear the blood more slowly than iodine agents, permitting longer imaging times. Gold nanoparticles, 1.9 nm in diameter, were injected intravenously into mice and images recorded over time with a standard mammography unit. Gold biodistribution was measured by atomic absorption. Retention in liver and spleen was low with elimination by the kidneys. Organs such as kidneys and tumours were seen with unusual clarity and high spatial resolution. Blood vessels less than 100 microm in diameter were delineated, thus enabling in vivo vascular casting. Regions of increased vascularization and angiogenesis could be distinguished. With 10 mg Au ml(-1) initially in the blood, mouse behaviour was unremarkable and neither blood plasma analytes nor organ histology revealed any evidence of toxicity 11 days and 30 days after injection. Gold nanoparticles can be used as X-ray contrast agents with properties that overcome some significant limitations of iodine-based agents.
Remarkable oxidative stability is shown by the carboxylate-functionalized primary bisphosphane 1. Compound 1 can be used in conjugation reactions with biomolecules for functionalization through the COOH group without prior protection of PH2 groups. A novel water-soluble bisphosphane was obtained by reaction of the PH2 groups of 1 with formaldehyde under mild conditions.
Eine bemerkenswerte Oxidationsbeständigkeit zeichnet das Carboxy-funktionalisierte primäre Bisphosphan 1 aus. Es kann über die COOH-Gruppe mit Biomolekülen zu Konjugaten verknüpft werden, ohne daß die PH2-Gruppen vorher geschützt werden müssen. Ein neuartiges, wasserlösliches Bisphosphan wurde durch die Reaktion der PH2-Gruppen von 1 mit Formaldehyd unter milden Bedingungen erhalten.
Six commercial gum arabic samples and authenticated samples of gum from Acacia senegal and Acacia seyal have been characterised using a range of chemical and physicochemical techniques including determination of specific rotation, sugar composition, nitrogen and amino acid content, and molecular mass distribution. Although some of the gums have slightly different chemical and physicochemical characteristics, gel permeation chromatography shows that each consists of essentially three molecular mass fractions classified as an arabinogalactan, an arabinogalactan-protein complex, and a glycoprotein. The proportions of each varied for the individual samples. The gums were tested using a specifically developed enzyme-linked immunosorbent assay which can identify gum from A. senegal and chemically related species. Their interaction with the antibody could be correlated with differences observed in their molecular compositions. Such evidence will assist in their chemotaxonomic classification.
IntroductionImmunogold-Silver Staining: A HistoryCombined Fluorescent and Gold ProbesMethodology Choice of Gold and AMG TypeIodinizationSensitivityApplications for the Microscopical Detection of AntigensDetection of Nucleic Acid SequencesApplications for Microscopical Detection of Nucleic AcidsTechnical Guidelines and Laboratory ProtocolsGold Derivatives of Other Biomolecules Protein LabelingGold Cluster-labeled PeptidesGold Cluster Conjugates of Other Small MoleculesGold–Lipids: MetallosomesLarger Covalent Particle LabelsGold Targeted to His TagsEnzyme MetallographyGold Cluster NanocrystalsGold Cluster–Oligonucleotide Conjugates: Nanotechnology Applications DNA Nanowires3-D Nanostructured Mineralized BiomaterialsGold-quenched Molecular BeaconsOther Metal Cluster Labels Platinum and PalladiumTungstatesIridium Choice of Gold and AMG TypeIodinizationSensitivity Protein LabelingGold Cluster-labeled PeptidesGold Cluster Conjugates of Other Small MoleculesGold–Lipids: Metallosomes DNA Nanowires3-D Nanostructured Mineralized BiomaterialsGold-quenched Molecular Beacons Platinum and PalladiumTungstatesIridium
Gum arabic (Acacia senegal gum) was fractionated by hydrophobic interaction chromatography on Phenyl-Sepharose CL-4B and yielded four fractions of similar carbohydrate composition, whilst differing in protein content, amino acid composition, and molecular mass distribution. All four fractions interacted with an array of anti-arabinogalactan-protein (AGP) monoclonal antibodies via anti-carbohydrate epitopes and were precipitated by Yariv's reagent, suggesting that they were all AGPs. Further characterisation using SDS-PAGE and Western blotting showed that all fractions contained proteins of molecular mass 30 000–45 000 with at least one protein unique to each fraction. The fractions were subjected to enzymatic (with pronase) and alkaline hydrolysis, and the molecular mass distribution of the products was monitored by gel permeation chromatography. The fractions showed various degrees of resistance to hydrolysis, thus illustrating differences in their macromolecular structure.
There have been substantial developments recently concerning the regulatory aspects of gum arable and the elucidation of its structure and functional characteristics. The aim of this paper is to present the position with regard to its current legal definition, to summarize what is now known about the structure of this complex polysaccharide and to illustrate how the structural features relate to its functional properties, notably its ability to stabilize oil-in-water emulsions and to form concentrated solutions of low viscosity.
Rationale and objectives:
We evaluated the efficacy of a particulate computed tomography (CT) contrast agent in an animal model of focal liver disease.
Methods:
Ethyl ester of diatrizoic acid (EEDA) is an iodinated (89 mg I/ml) nanoparticulate (200 nm) contrast agent intended for intravenous use that is currently undergoing preclinical testing in our laboratory. Focal liver abscesses were created in 11 New Zealand White rabbits. Iohexol and EEDA were administered to each animal on different days. CT scanning was performed at intervals following contrast agent administration. Liver and abscess enhancement were measured and compared. Dynamic imaging experiments in normal animals were also performed using both agents.
Results:
EEDA resulted in significantly greater enhancement of the liver and liver-to-abscess contrast than did iohexol at all time points beyond 5 min at approximately 25% of the total iodine load. During dynamic imaging, liver and aortic enhancement were greater with EEDA than with iohexol, except during a 20- to 40-sec period immediately following contrast agent administration.
Conclusion:
EEDA is superior to iohexol for imaging liver abscesses. Our results suggest that liver-directed agents such as EEDA may prove to be more efficacious than currently available extracellular agents designed for liver CT scanning.
Dual-phase dynamic helical CT is now being used to detect and characterize benign and malignant hypervascular lesions in the liver. The purpose of this study is to define the timing and degree of parenchymal enhancement of normal liver during the hepatic arterial phase.
This prospective study included 102 patients with known or suspected hypervascular hepatic lesions who underwent dual-phase helical CT. After unenhanced CT scanning, we injected iopamidol (Isovue 300; Bracco Diagnostics, Princeton, NJ) at 3 ml/sec for 120 ml, then at 2 ml/sec for 55-60 ml. Scan delay for the hepatic arterial phase was 25 sec and for the portal venous phase was 76 sec. Section thickness was 7 mm and pitch was 1:1. Operator-defined regions of interest were obtained from all three phases.
Mean unenhanced attenuation of the liver was 51 +/- 12 H. The liver revealed progressive enhancement during the hepatic arterial phase as follows: an increase of 10 H occurred at a mean time of 33 +/- 4 sec, 20 H at 39 +/- 6 sec, 30 H at 44 +/- 8 sec, 40 H at 46 +/- 6 sec, and 50 H at 48 +/- 5 sec. At 20 H and 30 H of enhancement, we found a statistically significant difference (p < .01) for the mean times of men and women. Mean peak enhancement during the portal venous phase was 89 +/- 23 H.
Because the hepatic arterial contribution to liver perfusion is approximately 30%, parenchymal enhancement greater than approximately 30% of peak might indicate portal venous predominance. In our study, this percentage corresponded to an increase of approximately 30 H. Therefore, detection of hypervascular lesions in the hepatic arterial phase may be compromised when imaging lasts longer than approximately 44 sec after the initiation of contrast material injection because 44 sec was the mean time for 30 H of enhancement in our series. However, variability between patients was marked, particularly between men and women. Furthermore, the data suggests that the hepatic arterial phase may be relatively brief and that it may be difficult to image properly using current helical CT technology.
We evaluated the effect of time and dose on lymph node iodine uptake after subcutaneous or submucosal administration of iodinated nanoparticles used for computed tomography lymphography.
We injected 0.1-6 ml of a 15% wt/vol iodinated nanoparticle suspension into the distal extremities subcutaneously (n = 5) or into the buccal submucosa (n = 7) of normal dogs. Precontrast and 4, 12, 24, and 48 hr after contrast administration, CT scans of opacified lymph nodes were obtained. Iodine concentration, node volume, and total iodine uptake were estimated for each node.
All estimated parameters increased between 4 and 12 hr postcontrast (p < .05), with no significant increase thereafter. At 24 hr postcontrast, iodine concentration ranged from 0.01 to 16.1 mg/ml (47-568 Hounsfield units). The average iodine concentration and total iodine uptake increased with contrast dose (p < .05) for all lymph node groups evaluated. Node opacification also revealed internal architectural detail.
Subcutaneous and submucosal injections of iodinated nanoparticles result in a dose-dependent iodine uptake in targeted lymph nodes. In addition, architectural detail within opacified nodes can be visualized.
The development of novel gold-198 complexes with water-soluble phosphines is reported. A series of cationic and hydrophilic 198Au complexes containing the ligands tris(hydroxymethyl)phosphine (THP, 1) 1,2-bis[bis(hydroxymethyl)phosphino]benzene (HMPB, 2), and 1,2-bis[bis(hydroxymethyl)phosphino]ethane (HMPE, 3) were prepared and evaluated as models for potential gold-199 radiopharmaceuticals. The 198Au complexes were formed in high radiochemical purity by simply mixing H198AuCl4 with the respective ligand. The complexes were shown to exhibit high in vitro stability over wide pH ranges and temperatures. However, only the 198Au(HMPB)2+ complex was found to exhibit good in vivo stability. HPLC analyses indicated that the 198Au complexes with these three phosphine ligands produced singular species with similar retention times as compared to their known macroscopic complexes.
To investigate the use of gadolinium as a computed tomographic (CT) contrast agent.
In vitro attenuation measurements of multiple dilutions of gadodiamide and ioversol were compared. In three pigs, 50-mL boluses of undiluted gadodiamide were injected intravenously at 2 mL/sec, and repeated single-level scans were obtained through the lung bases, liver, and kidneys. The doses of 0.8-1.0 mmol of gadolinium per kilogram of body weight were approximately three times the highest doses currently used in patients. Enhancement was determined from attenuation measurements in the aorta, pulmonary arteries, liver, and kidneys.
In vitro, the attenuation of undiluted gadodiamide (3,069 HU) was equivalent to that of ioversol diluted to 106 mg of iodine per milliliter and at equimolar concentrations was 50% greater than that of ioversol. The magnitude of and time to peak enhancement were 141 HU and 27 seconds (n = 3) for the aorta; 168 HU and 21 seconds (n = 3) for the pulmonary arteries; 23 HU and 65 seconds (n = 2) for the liver; and 63 HU and 32 seconds (n = 1) for the kidneys. Time-attenuation curves revealed a useful duration of enhancement of 20-30 seconds for the aorta and pulmonary arteries.
Gadolinium produces good vascular enhancement, adequate renal enhancement, and suboptimal hepatic enhancement. Further study is needed to determine the safety of the gadolinium dose required to produce similar enhancement in patients.
The Symposium New Frontiers in Gold Labeling was held at the Fifth Joint Meeting of the Japan Society of Histochemistry and Cytochemistry and the United States Histochemical Society. Speakers described technological developments in this area that improved localization of cellular components. Each presentation is summarized in this overview, and complete articles follow that describe these results in more detail.
Gum arabic glycoprotein (GAGP) is a large molecular weight, hydroxyproline-rich arabinogalactan-protein (AGP) component of gum arabic. GAGP has a simple, highly biased amino acid composition indicating a repetitive polypeptide backbone. Previous work (Qi, W., Fong, C., Lamport, D.T.A., 1991. Plant Physiology 96, 848), suggested small (approximately 11 residue) repetitive peptide motifs each with three Hyp-arabinoside attachment sites and a single Hyp-arabinogalactan polysaccharide attachment site. We tested that hypothesis by sequence analysis of the GAGP polypeptide after HF-deglycosylation. A family of closely related peptides confirmed the presence of a repetitive 19-residue consensus motif. However, the motif: Ser-Hyp-Hyp-Hyp-Thr-Leu-Ser-Hyp-Ser- Hyp-Thr-Hyp-Thr-Hyp-Hyp-Leu-Gly-Pro-His, was about twice the size anticipated. Thus, judging by Hyp-glycoside profiles of GAGP, the consensus motif contained six Hyp-arabinosides rather than three and two Hyp-polysaccharides rather than one. We inferred the glycosylation sites based on the Hyp contiguity hypothesis which predicts arabinosides on contiguous Hyp residues and arabinogalactan polysaccharides on clustered non-contiguous Hyp residues, i.e. the GAGP motif would consist of arabinosylated contiguous Hyp blocks flanking two central Hyp-polysaccharides. We predict this rigidifies the glycoprotein, enhances the overall symmetry of the glycopeptide motif, and may explain some of the remarkable properties of gum arabic.
The reactions of (HOCH2)2P(C6H4)P(CH2OH)2 (HMPB) and P(CH2OH)3 (THP) with RhCl3.xH2O in aqueous media gave water-soluble complexes cis-[RhCl2{eta2-(HOCH2)2P(C6H4)P(CH2OH)2}2]Cl (3) and fac-[RhCl3(P(CH2OH)3)3] (4) respectively in good yields, X-ray crystal structures of 3 and 4 confirmed their molecular constitution. These reactions provide the first examples demonstrating the kinetic propensity of hydroxymethyl phosphanes to stabilize Rh in +3 oxidation state in water.
Multiplexed detection of oligonucleotide targets has been performed with gold nanoparticle probes labeled with oligonucleotides
and Raman-active dyes. The gold nanoparticles facilitate the formation of a silver coating that acts as a surface-enhanced
Raman scattering promoter for the dye-labeled particles that have been captured by target molecules and an underlying chip
in microarray format. The strategy provides the high-sensitivity and high-selectivity attributes of gray-scale scanometric
detection but adds multiplexing and ratioing capabilities because a very large number of probes can be designed based on the
concept of using a Raman tag as a narrow-band spectroscopic fingerprint. Six dissimilar DNA targets with six Raman-labeled
nanoparticle probes were distinguished, as well as two RNA targets with single nucleotide polymorphisms. The current unoptimized
detection limit of this method is 20 femtomolar.
A novel hydrophilic gold compound, tetrakis((trishydroxymethyl)phosphine)gold(I) chloride 1, has been investigated for its antitumor properties. In vitro studies demonstrate that 1 is active against HCT-15, AGS, PC-3, and LNCaP tumor cells. Cell cycle analysis of the HCT-15 cells by flow cytometry revealed elongation of the G1 phase of the cell cycle leading to growth inhibition. Administration of 1 to Balb/C mice inoculated with syngenic meth/A cells demonstrated statistically significant dose-dependent survival time.
The ability of peptide-modified gold nanoparticles to target the nucleus of HepG2 cells was explored. Five peptide/nanoparticle complexes were investigated, particles modified with (1) the nuclear localization signal (NLS) from the SV 40 virus; (2) the adenovirus NLS; (3) the adenovirus receptor-mediated endocytosis (RME) peptide; (4) one long peptide containing the adenovirus RME and NLS; and (5) the adenovirus RME and NLS peptides attached to the nanoparticle as separate pieces. Gold nanoparticles were used because they are easy to identify using video-enhanced color differential interference contrast microscopy, and they are excellent scaffolds from which to build multifunctional nuclear targeting vectors. For example, particles modified solely with NLS peptides were not able to target the nucleus of HepG2 cells from outside the plasma membrane, because they either could not enter the cell or were trapped in endosomes. The combination of NLS/RME particles (4) and (5) did reach the nucleus; however, nuclear targeting was more efficient when the two signals were attached to nanoparticles as separate short pieces versus one long peptide. These studies highlight the challenges associated with nuclear targeting and the potential advantages of designing multifunctional nanostructured materials as tools for intracellular diagnostics and therapeutic delivery.
Microbeam radiation therapy is an experimental modality using parallel arrays of thin (<100 micro m) slices of synchrotron-generated X rays (microplanar beams, microbeams). We used EMT-6 murine mammary carcinoma subcutaneously inoculated in the hind legs of mice to compare the therapeutic efficacies of single-fraction, unidirectional (1) "co-planar" microbeams (an array of vertically oriented microplanar beams), (2) "cross-planar" microbeams (two arrays of parallel microbeams propagated in the same direction, one with vertically and the other with horizontally oriented microplanar beams), and (3) seamless (broad) beams from the same synchrotron source. The microbeams were 90 micro m wide and were spaced 300 micro m on center; the median energy in all beams was 100 or 118 keV. Tumor ablation rates were 4/8, 4/8 and 6/7 for a 410-, 520- and 650-Gy in-slice cross-planar microbeam dose, respectively, and 1/8, 3/8, 3/7 and 6/8 for a 23-, 30-, 38- and 45-Gy broad-beam dose, respectively. When the data were pooled from the three highest doses (same average tumor ablations of 50-60%), the incidences of normal-tissue acute toxicity (moist desquamation and epilation) and delayed toxicity (failure of hair regrowth) were significantly lower for cross-planar microbeams than broad beams (P < 0.025). Furthermore, for the highest doses in these two groups, which also had the same tumor ablation rate (>75%), not only were the above toxicities lower for the cross-planar microbeams than for the broad beams (P < 0.02), but severe leg dysfunction was also lower (P < 0.003). These findings suggest that single-fraction microbeams can ablate tumors at high rates with relatively little normal-tissue toxicity.
MU-Gold, tetrakis (trishydroxymethyl) phosphine gold(I) chloride, a novel gold compound, has cytotoxic effects against human androgen-dependent and -independent prostatic, gastric, and colonic carcinoma in cell culture and against malignant lymphoma in rodent models. A pilot study was conducted to evaluate the tolerance and pharmacokinetic properties of MU-Gold in normal dogs in anticipation of clinical trials in cancer-bearing dogs. MU-Gold (10 mg/kg) was administered by i.v. injection to three purpose-bred dogs. Serum was collected from all dogs for measurement of gold levels via atomic absorption spectrometry. In addition, complete blood counts and biochemical profiles were monitored for Dogs 2 and 3 every 7 days for 30 days. A two-compartment i.v. bolus model with first-order kinetics, mean elimination half-life of approximately 40 hours, and mean volume of distribution of 0.6 L/kg was established. Serum gold concentrations ranging from 10 to 50 mcg/ml were sustained for 2 to 3 days with no clinically significant toxicities observed. Based on in vitro results in earlier studies and preliminary pharmacokinetic data collected in the present study, Phase I clinical trials should be conducted to define the optimal dosage, dose-limiting toxicities, and other characteristics of MU-Gold that will be used to design Phase II clinical trials.
Phosphorus functionalized trimeric alanine compounds (l)- and (d)-P(CH(2)NHCH(CH(3))COOH)(3) 2 are prepared in 90% yields by the Mannich reaction of Tris(hydroxymethyl)phosphine 1 with (l)- or (d)- Alanine in aqueous media. The hydration properties of (l)-2 and (d)-2 in water and water-methanol mixtures are described. The crystal structure analysis of (l)-2.4H(2)O, reveals that the alanine molecules pack to form two-dimensional bilayers running parallel to (001). The layered structural motif depicts two closely packed monolayers of 2 each oriented with its phosphorus atoms projected at the center of the bilayer and adjacent monolayers are held together by hydrogen bonds between amine and carboxylate groups. The water bilayers are juxtaposed with the H-bonded alanine trimers leading to 18-membered (H(2)O)(18) water rings. Exposure of aqueous solution of (l)-2 and (d)-2 to methanol vapors resulted in closely packed (l)-2 and (d)-2 solvated with mixed water-methanol (H(2)O)(15)(CH(3)OH)(3) clusters. The O-O distances in the mixed methanol-water clusters of (l)-2.3H(2)O.CH(3)OH and (d)-2.3H(2)O.CH(3)OH (O-O(average) = 2.857 A) are nearly identical to the O-O distance observed in the supramolecular (H(2)O)(18) water structure (O-O(average) = 2.859 A) implying the retention of the hydrogen bonded structure in water despite the accommodation of hydrophobic methanol groups within the supramolecular (H(2)O)(15)(CH(3)OH)(3) framework. The O-O distances in (l)-2.3H(2)O.CH(3)OH and (d)-2.3H(2)O.CH(3)OH and in (H(2)O)(18) are very close to the O-O distance reported for liquid water (2.85 A).
Overdose of acetaminophen, a widely used analgesic drug, can result in severe hepatotoxicity and is often fatal. This study was undertaken to examine the effects of arabic gum (AG), which is commonly used in processed foods, on acetaminophen-induced hepatotoxicity in mice. Mice were given arabic gum orally (100 g l(-1)) 5 days before a hepatotoxic dose of acetaminophen (500 mg kg(-1)) intraperitoneally. Arabic gum administration dramatically reduced acetaminophen-induced hepatotoxicity as evidenced by reduced serum alanine (ALT) and aspartate aminotransferase (AST) activities. Acetaminophen-induced hepatic lipid peroxidation was reduced significantly by arabic gum pretreatment. The protection offered by arabic gum does not appear to be caused by a decrease in the formation of toxic acetaminophen metabolites, which consumes glutathione, because arabic gum did not alter acetaminophen-induced hepatic glutathione depletion. Acetaminophen increased nitric oxide synthesis as measured by serum nitrate plus nitrite at 4 and 6 h after administration and arabic gum pretreatment significantly reduced their formation. In conclusion, arabic gum is effective in protecting mice against acetaminophen-induced hepatotoxicity. This protection may involve the reduction of oxidative stress.
The radioactive gold grain applicator and seeds offer the flexibility necessary for effective use in the treatment of difficult sites of head-and-neck cancers. This study reviews our experience with gold grain (198Au) implants in locally advanced head-and-neck cancer to demonstrate their efficacy and feasibility.
This study reviewed the charts of 94 patients who were treated with gold grain implants (1970-1995) and who were treated with radioactive 198Au implants. Thirty-seven of the subjects had implants located in the head-and-neck region, and these form the basis for this report. Of these, eight of the cases were located in the supraglottic larynx, five in the nasopharynx, four in the retromolar trigone, two in the oral cavity, four in the base of the tongue, four in the maxillary antrum, four in the palate, two in metastatic cervical lymph nodes (of unknown primary tumor), two in the tonsillar fossa, one in the pyriform fossa, and one in the posterior pharyngeal wall. Twenty-eight were recurrent cases after prior surgeries and radiation. Six were residual locally advanced cases, and 3 patients had their implants for a second primary tumor in an area that had been irradiated before. The gold grains were inserted with a Royal Marsden gun and 198Au, 130-180 MBq per seed. The median number of seeds implanted was 34. The total radiation dose, delivered at a margin of 0.5 cm around the target volume, ranged from 40 to 120 Gy, with a median of 80 Gy.
Complete local control was achieved in 33% and was contingent on two factors: (1) the size of the lesion implanted and (2) the histology and possible primary tumor site. In 19 tumors with a diameter greater than 2.5 cm, only 2 (11%) had complete tumor control. Conversely, 9 of 14 patients (64%) who had lesions smaller than 2.5 cm experienced successful local control (p = 0.002). Palatal-adenoid-cystic tumors had an average progression-free survival of 52 months, compared with 13, 9, and 4 months, respectively, in nasopharyngeal, oropharyngeal, and supraglottic squamous cell carcinoma. Palliation was successfully accomplished in 76% of the cases. Cessation of bleeding occurred in 50% of the subjects, pain control was achieved in 88%, and 60% experienced relief of dysphagia.
Gold grain implants have a role in the palliation of recurrent head-and-neck tumors, particularly for sites difficult to reach via other techniques, such as the supraglottic larynx, base of the tongue, hypopharynx, and the nasopharynx. Local control is best achieved in lesions less than 2.5 cm in dimension and is most successful in slow-growing tumors.
The following study examines the feasibility of nanoshell-assisted photo-thermal therapy (NAPT). This technique takes advantage of the strong near infrared (NIR) absorption of nanoshells, a new class of gold nanoparticles with tunable optical absorptivities that can undergo passive extravasation from the abnormal tumor vasculature due to their nanoscale size. Tumors were grown in immune-competent mice by subcutaneous injection of murine colon carcinoma cells (CT26.WT). Polyethylene glycol (PEG) coated nanoshells (approximately 130 nm diameter) with peak optical absorption in the NIR were intravenously injected and allowed to circulate for 6 h. Tumors were then illuminated with a diode laser (808 nm, 4 W/cm2, 3 min). All such treated tumors abated and treated mice appeared healthy and tumor free >90 days later. Control animals and additional sham-treatment animals (laser treatment without nanoshell injection) were euthanized when tumors grew to a predetermined size, which occurred 6-19 days post-treatment. This simple, non-invasive procedure shows great promise as a technique for selective photo-thermal tumor ablation.
Gum arabic, a branched polysaccharide, was oxidized using periodate to generate reactive aldehyde groups on the biopolymer. Primaquine, an 8-aminoquinoline, was covalently coupled onto oxidized gum arabic via an imine bond and simultaneously fabricated into microspheres of less than 2 microm in size by heat denaturation in a reverse emulsion of 1:1 light paraffin oil and toluene stabilized by sorbitan sesquioleate as the surfactant. The covalent binding of primaquine to the polysaccharide using the clinically used water-soluble form of the drug primaquine phosphate was achieved in the presence of borate buffer of pH 11. Up to 35% of the drug could be bound to the polymer backbone depending on the concentration of the drug employed initially and the degree of oxidation of the polysaccharide. Interestingly, both the aliphatic and the hindered aromatic amino groups of primaquine were found to react with the aldehyde functions through Schiff base formation leading to cross-linking of the polysaccharide with the drug itself. In vitro release of the drug from microspheres into phosphate buffered saline (PBS, pH 7.4, 0.1 M) at 37 degrees C showed that the release of primaquine from the matrix was slow, although gradually increased with time. The maximum released was below 50% of the drug payload even after 10 days. Release into simulated gastric and intestinal fluids was faster compared to the release in PBS due to rapid hydrolysis of the Schiff's linkage in the gastric fluid. A possible reason for the poor hydrolytic susceptibility of the Schiff's linkage is suggested based on the unequal reactivity of the amino groups on primaquine and its relevance in possible therapeutic application of this polymer-drug conjugate discussed.
We find that single- and double-stranded oligonucleotides have different propensities to adsorb on gold nanoparticles in colloidal solution. We use this observation to design a hybridization assay based on color changes associated with gold aggregation. Because the underlying adsorption mechanism is electrostatic, no covalent functionalization of the gold, the probe, or the target DNA is required. Hybridization conditions can be optimized because it is completely separated from the detection step. The assay is complete within 5 min, and <100 femtomoles of target produces color changes observable without instrumentation. Single-base-pair mismatches are easily detected.
Mice bearing subcutaneous EMT-6 mammary carcinomas received a single intravenous injection of 1.9 nm diameter gold particles (up to 2.7 g Au/kg body weight), which elevated concentrations of gold to 7 mg Au/g in tumours. Tumour-to-normal-tissue gold concentration ratios remained approximately 8:1 during several minutes of 250 kVp x-ray therapy. One-year survival was 86% versus 20% with x-rays alone and 0% with gold alone. The increase in tumours safely ablated was dependent on the amount of gold injected. The gold nanoparticles were apparently non-toxic to mice and were largely cleared from the body through the kidneys. This novel use of small gold nanoparticles permitted achievement of the high metal content in tumours necessary for significant high-Z radioenhancement.
Swelling (and shrinking) of poly(2-vinylpyridine), P2VP, polymer brushes, caused by pH changes, could be readily monitored by transmission surface plasmon resonance, T-SPR, spectroscopy. Gold nanoparticles attached to the P2VP polymer brushes dramatically enhanced the pH-induced shift in the T-SPR absorption spectra. (A 50 nm shift of the absorption maximum of the T-SPR spectrum of the supporting gold nanoislands was observed upon changing the pH from 5.0 to 2.0, corresponding to a swelling of the polymer brushes from 8.1 +/- 0.7 to 24.0 +/- 2.0 nm. Same shift in the opposite direction was observed upon changing the pH from 2.0 to 5.0.)
Design and synthesis of chelating bisphosphines functionalized with the smallest chemical unit "H" on the P(III) centers ((PH(2)CH(2))(2)CHCH(2)NHPh (4) and (PH(2)CH(2))(2)CHCONHPh (5)) are described. Studies demonstrating that no bulky chemical substituents are necessary to offer thermal/oxidative stability to the -PH(2) groups in 4 and 5 are described. The H atoms around the P(III) centers in 5 (or 4) concur limited/no steric influence, but yet the phosphines manifest high nucleophilicity to coordinate strongly with W(0) and Re(I). The studies include synthesis and X-ray structural characterization of an air-stable primary bisphosphine (5) and its transition-metal chemistry with W(CO)(6) and Re(CO)(5)Br to produce the complexes (eta(2)-(PH(2)CH(2))(2)CHCONHPh)W(CO)(4) (6) and (eta(2)-(PH(2)CH(2))(2)CHCONHPh)Re(CO)(3)Br (7), respectively.
An inhibition assay method was developed based on the modulation in the FRET efficiency between quantum dots (QDs) and gold nanoparticles (AuNPs) in the presence of the molecules which inhibit the interactions between QD- and AuNP-conjugated biomolecules. For the functionalization, AuNPs were first stabilized by chemisorption of n-alkanethiols and then capped with the first generation polyamidoamine (G1 PAMAM) dendrimers. By employing a streptavidin-biotin couple as a model system, avidin was quantitatively analyzed as an inhibitor by sensing the change in photoluminescence (PL) quenching of SA-QDs by biotin-AuNPs. The detection limit for avidin was about 10 nM. It is anticipated that the PL quenching-based sensing system can be used for the quantitative analysis and high throughput screening of molecules which inhibit the specific biomolecular interactions.
A recent mice study demonstrated that gold nanoparticles could be safely administered and used to enhance the tumour dose during radiation therapy. The use of gold nanoparticles seems more promising than earlier methods because of the high atomic number of gold and because nanoparticles can more easily penetrate the tumour vasculature. However, to date, possible dose enhancement due to the use of gold nanoparticles has not been well quantified, especially for common radiation treatment situations. Therefore, the current preliminary study estimated this dose enhancement by Monte Carlo calculations for several phantom test cases representing radiation treatments with the following modalities: 140 kVp x-rays, 4 and 6 MV photon beams, and 192Ir gamma rays. The current study considered three levels of gold concentration within the tumour, two of which are based on the aforementioned mice study, and assumed either no gold or a single gold concentration level outside the tumour. The dose enhancement over the tumour volume considered for the 140 kVp x-ray case can be at least a factor of 2 at an achievable gold concentration of 7 mg Au/g tumour assuming no gold outside the tumour. The tumour dose enhancement for the cases involving the 4 and 6 MV photon beams based on the same assumption ranged from about 1% to 7%, depending on the amount of gold within the tumour and photon beam qualities. For the 192Ir cases, the dose enhancement within the tumour region ranged from 5% to 31%, depending on radial distance and gold concentration level within the tumour. For the 7 mg Au/g tumour cases, the loading of gold into surrounding normal tissue at 2 mg Au/g resulted in an increase in the normal tissue dose, up to 30%, negligible, and about 2% for the 140 kVp x-rays, 6 MV photon beam, and 192Ir gamma rays, respectively, while the magnitude of dose enhancement within the tumour was essentially unchanged.
In late August, behind closed doors at the austere National Academy of Sciences in Washington D.C., Samuel Stupp, a materials scientist and director of the Institute for BioNanotechnology in Medicine at Northwestern University, showed a video clip for a committee evaluating the United States' billion-dollar-a-year National Nanotechnology Program.