ArticleLiterature Review

Nanotechnological applications in medicine, Curr. Opin. Biotechnol. 18(1), 26

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Abstract

Nanotechnology-based tools and techniques are rapidly emerging in the fields of medical imaging and targeted drug delivery. Employing constructs such as dendrimers, liposomes, nanoshells, nanotubes, emulsions and quantum dots, these advances lead toward the concept of personalized medicine and the potential for very early, even pre-symptomatic, diagnoses coupled with highly-effective targeted therapy. Highlighting clinically available and preclinical applications, this review explores the opportunities and issues surrounding nanomedicine.

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... It concerns a range of particles, which should be at the nanoscale, between 1 and 1000 nm [56][57][58][59][60]. The goals of nanomedicine are common to those of traditional medicine, being earlier diagnosis, the development of non-invasive and effective treatments, and the minimization of side effects [57]. ...
... Like nanotechnology, the definition of nanomedicine is not agreed on. It concerns a range of particles, which should be at the nanoscale, between 1 and 1000 nm [56][57][58][59][60]. The goals of nanomedicine are common to those of traditional medicine, being earlier diagnosis, the development of non-invasive and effective treatments, and the minimization of side effects [57]. ...
... It concerns a range of particles, which should be at the nanoscale, between 1 and 1000 nm [56][57][58][59][60]. The goals of nanomedicine are common to those of traditional medicine, being earlier diagnosis, the development of non-invasive and effective treatments, and the minimization of side effects [57]. Nanomedicine offers not only improvements for existing techniques, but also the possibility of developing new techniques with superior efficacy, by manipulating drugs at the molecular level and altering their physicochemical properties, such as their solubility and permeability; or facilitating their sustained or controlled delivery [56,57]. ...
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Head and neck cancers rank sixth among the most common cancers today, and the survival rate has remained virtually unchanged over the past 25 years, due to late diagnosis and ineffective treatments. They have two main risk factors, tobacco and alcohol, and human papillomavirus infection is a secondary risk factor. These cancers affect areas of the body that are fundamental for the five senses. Therefore, it is necessary to treat them effectively and non-invasively as early as possible, in order to do not compromise vital functions, which is not always possible with conventional treatments (chemotherapy or radiotherapy). In this sense, nanomedicine plays a key role in the treatment and diagnosis of head and neck cancers. Nanomedicine involves using nanocarriers to deliver drugs to sites of action and reducing the necessary doses and possible side effects. The main purpose of this review is to give an overview of the applications of nanocarrier systems to the diagnosis and treatment of head and neck cancer. Herein, several types of delivery strategies, radiation enhancement, inside-out hyperthermia, and theragnostic approaches are addressed.
... Nanotechnology is an emerging field of science finds application in diagnostic and therapeutic approaches. Nanoparticles (NPs) are being used in diagnostic imaging and effective targeted drug delivery [9]. The nanoparticles are synthesized from plants, seaweeds, bacteria, fungi, and algae by the biological synthesis method. ...
... Metallic nanoparticles can be synthesized by using different methods, i.e., chemical and biochemical synthesis which normally uses alkyl mercaptan, polyvinylpyrrolidone, Nanotechnology is an emerging field of science finds application in diagnostic and therapeutic approaches. Nanoparticles (NPs) are being used in diagnostic imaging and effective targeted drug delivery [9]. The nanoparticles are synthesized from plants, seaweeds, bacteria, fungi, and algae by the biological synthesis method. ...
Article
Citation: Kiani, B.H.; Haq, I.-u.-; Alhodaib, A.; Basheer, S.; Fatima, H.; Naz, I.; Ur-Rehman, T. Comparative Evaluation of Biomedical Applications of Zinc Nanoparticles Synthesized by Using Withania somnifera Plant Extracts. Plants 2022, 11, 1525. https://doi.
... Nanotechnology is an emerging field of science finds application in diagnostic and therapeutic approaches. Nanoparticles (NPs) are being used in diagnostic imaging and effective targeted drug delivery [9]. The nanoparticles are synthesized from plants, seaweeds, bacteria, fungi, and algae by the biological synthesis method. ...
... Metallic nanoparticles can be synthesized by using different methods, i.e., chemical and biochemical synthesis which normally uses alkyl mercaptan, polyvinylpyrrolidone, Nanotechnology is an emerging field of science finds application in diagnostic and therapeutic approaches. Nanoparticles (NPs) are being used in diagnostic imaging and effective targeted drug delivery [9]. The nanoparticles are synthesized from plants, seaweeds, bacteria, fungi, and algae by the biological synthesis method. ...
Article
Full-text available
Green synthesis of metal nanoparticles is of great importance in the modern health care system. In this study, zinc nanoparticles (ZnONPs) were synthesized using leaf and root extracts of Withania somnifera using four different solvents. ZnONPs were characterized by UV-vis spec�trophotometer with a range between 350–400 nm. Scanning electron microscope revealed spherical morphology with an overall size of 70–90 nm and XRD pattern confirmed the crystalline structure. The total flavonoids, phenolic, and alkaloid contents were significantly greater in the crude extracts as compared to ZnONPs. The highest scavenging activity was observed in ZnONPs from n-hexane and ethyl-acetate extracts of roots with IC50 values of 27.36 µg/mL and 39.44 µg/mL, respectively. ZnONPs from methanol and aqueous extracts showed significant antibacterial activity against Es�cherichia coli, Staphylococcus aureus, and Bacillus subtilis while none of the extracts were found to have significant antifungal activity. Maximum cytotoxic activity was observed in ZnONPs synthe�sized from aqueous and n-hexane root extracts with LC50 values of 9.36 µg/mL and 18.84 µg/mL, respectively. The highest antidiabetic potential was exhibited by ZnONPs from n-hexane leaf ex�tracts, i.e., 47.67 ± 0.25%. Maximum protein kinase inhibitory potential was observed in ZnONPs of ethyl-acetate extract of roots with a bald zone of 12 mm. These results indicated that Withania somnifera-based ZnONPs showed significant biological activities compared to crude extracts. These findings can further be utilized for in-vivo analysis of nano-directed drug delivery systems.
... Semiconducting character and optical properties depend on the inorganic core. In QDs synthesis, the organic surfactants are developed and eventually shape ligands on the core surface [14][15][16][17]. The nature of the capping agent produced significantly relies on the final application of QDs. ...
... In the previous decade, with the development of surface modification technique, QDs with water-soluble capping stabilizer, for example, polyethylene glycol polymer, mercaptoethylamine, and mercaptoacetic acid are conjugate promptly with drug molecules through electrostatic interaction or covalent bonds, giving complex nanomedicine with QDs as drug carriers [8,14,22,24]. ...
Article
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In the twenty-first century, nanotechnology has become cutting-edge technology. It is interdisciplinary and multidisciplinary, covering numerous fields such as medicine, engineering, biology, physics, material sciences, and chemistry. The present work aims to cover the optical properties, method of preparations, surface modifications, bio-conjugation, characterization, stability, and cytotoxicity of quantum dots (QDs). Articles were reviewed in English literature reporting the pharmaceutical and bio-pharmaceutical aspects of QDs which were indexed in Scopus, web of science, google scholar and PubMed without applying the year of publication criterion. One significant value of utilizing nanotechnology is that one can alter and control the properties in a genuinely unsurprising way to address explicit applications' issues. In science and biomedicine, the usage of functional nanomaterials has been broadly investigated and has become one of the quick-moving and stimulating research directions. Different types of nanomaterial (silicon nanowires, QDs, carbon nanotubes, nanoparticles of gold/silver) were extensively utilized for biological purposes. Nanomedicine shows numerous advantages in the natural characteristics of targeted drug delivery and therapeutics. For instance, protection of drugs against degradation, improvement in the drug's stability, prolonged circulation time, deceased side effects, and enhanced distribution in tissues. The present review article deals with the quantum dots, their optical properties, method of preparations, surface modifications, bio-conjugation, characterization, stability, and cytotoxicity of quantum dots. The review also discusses various biomedical applications of QDs. The QDs-based bio-nanotechnology will always be in the growing list of unique applications, with progress being made in specialized nanoparticle development, the detection of elegant conjugation methods, and the discovery of new targeting ligands.
... 6,7 Many researchers have employed iron oxide nanoparticles thoroughly because of their unique properties such as low Curie temperature, high magnetic susceptibility, high surface area-to-volume ratio, high surface energy, tunable pore size, and uniform distribution, which provide a high demand for in vivo and in vitro application in the field of biomedical science to targeted drug delivery, 8 magnetic resonance imaging (MRI), 9 cancer hyperthermia, 10 catalysis, 11 biosensing, 12 environmental remediations, 13 and other industrial applications. 14 The use of iron nanoparticles in the biomedical field has led to significant advantages in terms of diagnosis, 15−20 biomedical detection, 21,22 therapy, 17 and drug delivery. 14,23 The surface morphology and particle size of iron/ iron oxide NPs could easily be controlled by a suitable synthetic method, which provides a specific application. ...
... 14 The use of iron nanoparticles in the biomedical field has led to significant advantages in terms of diagnosis, 15−20 biomedical detection, 21,22 therapy, 17 and drug delivery. 14,23 The surface morphology and particle size of iron/ iron oxide NPs could easily be controlled by a suitable synthetic method, which provides a specific application. 15 There are a few reports in the literature on the synthesis of iron oxide NPs, with limited applications because of large agglomeration and difficulty with dispersion in an aqueous medium, which prohibits in vitro application. ...
Article
Full-text available
In the present work, iron nanoparticles were synthesized in the α-Fe2O3 phase with the reduction of potassium hexachloroferrate(III) by using l-ascorbic acid as a reducing agent in the presence of an amphiphilic non-ionic polyethylene glycol surfactant in an aqueous solution. The synthesized α-Fe2O3 NPs were characterized by powder X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, atomic force microscopy, dynamic light scattering, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and ultraviolet-visible spectrophotometry. The powder X-ray diffraction analysis result confirmed the formation of α-Fe2O3 NPs, and the average crystallite size was found to be 45 nm. The other morphological studies suggested that α-Fe2O3 NPs were predominantly spherical in shape with a diameter ranges from 40 to 60 nm. The dynamic light scattering analysis revealed the zeta potential of α-Fe2O3 NPs as -28 ± 18 mV at maximum stability. The ultraviolet-visible spectrophotometry analysis shows an absorption peak at 394 nm, which is attributed to their surface plasmon vibration. The cytotoxicity test of synthesized α-Fe2O3 NPs was investigated against human carcinoma A549 lung cancer cells, and the biological adaptability exhibited by α-Fe2O3 NPs has opened a pathway to biomedical applications in the drug delivery system. Our investigation confirmed that l-ascorbic acid-coated α-Fe2O3 NPs with calculated IC50 ≤ 30 μg/mL are the best suited as an anticancer agent, showing the promising application in the treatment of carcinoma A549 lung cancer cells.
... There are various synthesis methods used in preparation of nanoparticles namely, chemical method, sol-gel method, microwave irradiation, biosynthesis method, hydrothermal and conventional precipitation [10][11][12][13][14][15][16][17][18][19][20][21]. The biosynthesis method is one of the best efficient and ecofriendly methods for synthesizing the nanoparticles [22][23][24][25][26]. It was believed that source of material, growth temperature, and vapor pressure concentration strongly influence the final shape and size of nano structure [27]. ...
Article
Full-text available
In this study, porous zinc oxide (ZnO) nanoparticles were prepared by using Green Synthesis method at different temperatures. Leaf extract from Eucalyptus Globulus plant was used as a reducing agent. Prepared powder was characterised using SEM, XRD, FTIR and MTT assay. XRD confirms the ZnO characteristic structure, FTIR gives the functional molecules picture and SEM confirm the nano size of the particle. MTT assay and antibacterial studies have shown good results on cell viability and antimicrobial properties of the material. A slight change in the particle size and significant change in the functional group was observed with variation of temperature. From the result obtained it is advised that ZnO nanoparticle can be used effectively in agriculture, food safety and medical science because of non-toxic residues post synthesis.
... A technology producing an ultra-dispersed solid supramolecular structure having a size from 10 to 1000 nm is called as nanotechnology which control the matter to nanometer-length scale leading to formation of nanoparticles (NPs). The technology is developing faster in various fields for example targeted drug delivery and medical imaging [79,80]. However, the application of nano-drug delivery system can successfully overwhelm the limitations of chemotherapy, decrease the toxicity of drugs, and thus raise the efficiency of anti-tumor agents [81]. ...
Article
Pancreatic cancer kills countless people every year throughout the globe and persists as one of the extremely lethal diseases that need foremost attention because the overall endurance percentage of pancreatic cancer is very little. Early diagnosis and efficient treatments are two of the biggest hurdles in the fight towards cancer. In the present work, we have reviewed thriving strategies concerning the pancreatic cancer therapy and thoroughly described the most recent developments in emerging modern drug delivery systems focused on and derived from nanotechnology. Recent advances in nanotechnology-based drug delivery systems have aimed to boost cellular uptake, improve pharmacokinetics and effectiveness of anti-cancer drugs, which consequently have assisted in potent attacking of specific agents for effectual pancreatic cancer therapy. Present review furnishes an insight into current progresses on potential curative targets for pancreatic cancer treatment. This knowledge might be useful as a basis for the potential development of multi-functional nano-constructions for advanced detection of pancreatic cancer as well as its efficient therapy.
... Due to their uses in medicine, biology, and material science, metal nanoparticles have stimulated the interest of scientific researchers. Noble metals such as gold and silver offer a lot of potential in biomedical applications, not only for delivering pharmaceutics but also for developing new diagnostic and therapeutic agents [32,33]. ...
Article
Full-text available
Liver and kidney diseases are the most frequently encountered problems around the globe. Damage to the liver and kidney may occur as a result of exposure to various drugs, chemicals, toxins, and pathogens, leading to severe disease conditions such as cirrhosis, fibrosis, hepatitis, acute kidney injury, and liver and renal failure. In this regard, the use of nanoparticles (NPs) such as silver nanoparticles (AgNPs), gold nanoparticles (AuNPs), and zinc oxide nanoparticles (ZnONPs) has emerged as a rapidly developing field of study in terms of safe delivery of various medications to target organs with minimal side effects. Due to their physical characteristics, NPs have inherent pharmacological effects, and an accidental buildup can have a significant impact on the structure and function of the liver and kidney. By suppressing the expression of the proinflammatory cytokines iNOS and COX-2, NPs are known to possess anti-inflammatory effects. Additionally, NPs have demonstrated their ability to operate as an antioxidant, squelching the generation of ROS caused by substances that cause oxidative stress. Finally, because of their pro-oxidant properties, they are also known to increase the level of ROS, which causes malignant liver and kidney cells to undergo apoptosis. As a result, NPs can be regarded as a double-edged sword whose inherent therapeutic benefits can be refined as we work to comprehend them in terms of their toxicity.
... By delivering pharmacologically active agents more effectively and more selectively to pathological sites (site-specific drug delivery) and/or by guiding them away from potentially endangered healthy tissues (site-avoidance drug delivery), nanomedicines aim to improve the balance between efficacy and the toxicity of systemic therapeutic interventions (Lammers, Hennink, & Storm, 2008;Sanhai, Sakamoto, Canady, & Ferrari, 2008). Besides, for drug targeting to pathological sites and for therapeutic purposes, nanomedicine formulations have also been used increasingly for imaging applications as well as, in the past few years, for theranostic approaches, that is, for systems and strategies in which disease diagnosis and therapy are combined (Caruthers, Wickline, & Lanza, 2007;Sun, 2010;Xie, Lee, & Chen, 2010). Classical drug delivery systems, and antibodies (Lammers, Aime, Hennink, Storm, & Kiessing, 2011), are being coloaded with drugs and contrast agents; examples of which are shown in Fig. 5.1. ...
Chapter
Oral and throat cancers are heterogeneous diseases encompassing a variety of aggressive tumors of the head and neck area with high morbidity, mortality, and recurrence. Early detection, diagnosis, and treatment are essential to minimizing morbidity and mortality. Conventional treatments involve surgical resection of large tumor areas followed by nonselective radiation therapy or chemotherapy, which cause severe side effects such as mucositis, maxillary osteonecrosis, hypocellularity, nephrotoxicity, and local tissue hypoxia, which affect quality of life. Adverse effects can occur because the components in the tumor microenvironment (TME) form physical/biological barriers making difficult the diffusion of therapeutic molecules and contributing to resistance and immunosuppression. Nanotechnology offers the potential to overcome many of the problems associated with conventional treatments and the capability to detect and treat cancer simultaneously. New nano delivery strategies of bioactive molecules have greatly impacted diagnostics through the use of molecular imaging, which can reliably distinguish between malignant and benign cells. Targeting cancer and releasing therapeutic molecules in response to TME with nanoparticles lead to potent antitumor efficacy and stimulate antitumor immunity. The present chapter reviews the state of the art of nano strategies and current clinical applications to target oral and throat cancers for diagnosis and treatment.
... As outlined in Figure 2, nanotechnology has wide-spread applications in biological system such as biomarkers, imaging, diagnostics, and therapeutics. Advances in medical imaging through nanomaterial-based technologies have led to improved results in optical, nuclear, ultrasound, and magnetic resonance imaging (MRI) [35][36][37]. Some of the earliest advances made use of paramagnetic iron oxide particles to image cancerous tissue in lymph nodes [38]. ...
Article
Full-text available
Human induced pluripotent stem cells (HiPSCs) and HiPSCs-derived cells have the potential to revolutionize regenerative and precision medicine. Genetically reprograming somatic cells to generate HiPSCs and genetic modification of HiPSCs are considered the key procedures for the study and application of HiPSCs. However, there are significant technical challenges for transgene delivery into somatic cells and HiPSCs since these cells are known to be difficult to transfect. The existing methods, such as viral transduction and chemical transfection, may introduce significant alternations to hiPSC culture which affect the potency, purity, consistency, safety, and functional capacity of HiPSCs. Therefore, generation and genetic modification of HiPSCs through non-viral approaches are necessary and desirable. Nanotechnology has revolutionized fields from astrophysics to biology over the past two decades. Increasingly, nanoparticles have been used in biomedicine as powerful tools for transgene and drug delivery, imaging, diagnostics, and therapeutics. The most successful example is the recent development of SARS-CoV-2 vaccines at warp speed to combat the 2019 coronavirus disease (COVID-19), which brought nanoparticles to the center stage of biomedicine and demonstrated the efficient nanoparticle-mediated transgene delivery into human body. Nanoparticles have the potential to facilitate the transgene delivery into the HiPSCs and offer a simple and robust approach. Nanoparticle-mediated transgene delivery has significant advantages over other methods, such as high efficiency, low cytotoxicity, biodegradability, low cost, directional and distal controllability, efficient in vivo applications, and lack of immune responses. Our recent study using magnetic nanoparticles for transfection of HiPSCs provided an example of the successful applications, supporting the potential roles of nanoparticles in hiPSC biology. This review discusses the principle, applications, and significance of nanoparticles in the transgene delivery to HiPSCs and their successful application in the development of COVID-19 vaccines.
... It is emerging with its applications in science and technology for the purpose of manufacturing new materials. Nanoparticles could reach a biological target of interest by having a small size and offers a great possibility for biomedical applications, not only to deliver pharmaceutics, but also to be used as novel diagnostic and therapeutic approaches [10] . In recent years, many environment friendly methods have been employed for the synthesis of nanoparticles. ...
Article
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Kamradgi et al.: Synthesis of Silver Nanoparticles from Wheatgrass Extract Wheatgrass extract was used for eco-friendly extracellular synthesis of silver nanoparticles. Stable silver nanoparticles were formed by treating the wheatgrass extract with aqueous silver nitrate solution as reducing agents. Ultraviolet-visible spectroscopy was used to confirm the presence of silver nanoparticles. The X-ray diffraction analysis exhibited characteristic peaks signifying the crystalline nature of nanoparticels. The particle size and the involvement of various biomolecules in the synthesis of silver nanoparticles were determined using Atomic force microscopy and Fourier transform infrared spectroscopy, respectively. The particle structure was studied by scanning electron microscopy and the elemental silver present in reaction mixture was confirmed by Energy dispersive x-ray. The nanoparticles were tested for their anticandidal activity against Candida albicans MTCC3017, Candida albicans MTCC1637, Candida albicans MTCC183, Candida tropicalis MTCC230 and Candida glabrata MTCC3814 and determined their minimum inhibitory concentration.
... If a chemical reaction is trapped inside such a chamber, then the chamber is considered a nanoreactor. The advantages of using nano-reactors can be more control over the reaction, selectivity, separation of toxic and unstable substances from the bulk medium, followed by reducing the toxicity of the system or increasing the stability of the catalyst and being ideal in processes such as drug delivery (Caruthers et al., 2007;Kim et al., 2010;Ostafin and Landfester, 2009). The reason for their small size, he pointed out, and on the other hand, in today's world, the need for early diagnosis of diseases and health conditions is increasing, because prevention is always better than cure. ...
Article
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In general, nanostructured materials with specific size, shape and geometry have unique and different properties from bulk materials. Using reaction media with nanometer and micrometer dimensions, they can produce new nanomaterials with interesting and remarkable properties. In general, nano-reactors are nanometer-sized chambers in which chemical reactions can take place. of course, nanoreactors are somehow part of the reaction, and this is the main difference between them and micro-reactors. One of the useful solutions to achieve the environment of nanoreactors is the use of porous materials, so due to the importance of nanoreactors, porous structures of silicate and zeolite are among the most prominent and widely used compounds in this group.
... Dx) and(1)(2)(3)(4)(5) shows the FTIR-spectra of dextrin and magnetite-NPs coated with dextrin in the range of 4000-400 cm -1 Wavenumber range. The magnetite-NPs show a high intensity band spectrum at 576 cm -1 which corresponds to the stretching vibration of Fe-O from Fe3O4 (Z.P.Yang et al., 2010). ...
Article
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We have developed a simple and easy Optimized-Reverse-Co-Precipitation Method (ORCPM) for the synthesis of Magnetite-Nanoparticles. This technique decreases the chances of agglomeration, broad particle size distribution and provides better nanoparticles as compared to simple co-precipitation method. The effect of different variables such as the temperature, N 2-sparging, stirring rate, amount of capping agent and pH were studied and optimized for the synthesis of Magnetite-NPs by using the proposed method. Among these reactions each with varying parameters, we finally concluded that the best Optimized-Conditions for the synthesis of M-NPs were 0.2g Dextrin at 60℃ with 12 pH, stirring rate of 150 rpm and with the continuous nitrogen sparging, can give far better results than the existing co-precipitation technique. The synthesized M-NPs were characterized using Fourier Transform Infrared Spectroscopy, X-Ray Diffractometer, Scanning Electron Microscope and Zeta-Potential. It was found that synthesized Magnetite-NPs with current technique were of FCC-shape with an average particle size of 12.9nm.
... As outlined in Fig. 2.1, nanotechnology in biology has wide-spread applications in biomarkers, imaging, diagnostics, therapeutics, and precision medicine. Advances in medical imaging through nanomaterial-based technologies have led to improved results in optical, nuclear, ultrasound, and magnetic resonance imaging (MRI) alike (Caruthers et al., 2007). Some of the earliest advances made use of paramagnetic iron oxide particles to image cancerous tissue in lymph nodes (Weissleder et al., 1990). ...
Chapter
In 2006, Takahashi and Yamanaka reported the generation of mouse and human induced pluripotent stem cells (iPS cells) by retroviral gene transduction of four transcription factors, famously known as Yamanaka factors (OCT4, SOX2, Klf4, and c-Myc) (Takahashi et al., 2007; Takahashi and Yamanaka, 2006). iPS cells show stemness properties (self-renewal and differentiation into three germ layers derivatives) that are comparable to the embryonic stem cells (ES cells). However, conventional iPS cells technique is not entirely safe because of its procedural difficulties, lower efficiency, and the risk of cancer formation (Luo et al., 2013; Rais et al., 2013). Meanwhile, several bacteria-mediated strategies have been identified that can reprogram differentiated cells into stem cell–like state and dedifferentiate into three germ layer derived cells. In 2012, Fuji et al. reported Helicobacter pylori bacteria can reprogram gastric epithelial cells into intestinal stem/progenitor-like cells in vivo by inducing homeobox transcription factors (CDX) during intestinal metaplasia (Fujii et al., 2012). In the same year, our group discovered that lactic acid bacteria (LAB) can reprogram human dermal fibroblast (HDF) into stem cell–like cells in vitro that can differentiate into all three germ layer derivatives (Ohta et al., 2012). Later, Masaki et al. reported that leprosy-causing bacterium Mycobacterium leprae reprograms adult Schwann cells into stem cell–like cells in vivo that differentiate into mesenchymal, skeletal, and smooth muscle cells facilitating infection dissemination (Masaki et al., 2013). In 2017, Ikeda et al. reported that Wolbachia pipientis bacterial proteins can accelerate traditional retroviral-mediated iPS cells generation process (Ikeda et al., 2017). All these studies substantiate the epigenetic potentials of bacteria or its material to induce stemness in differentiated cells. Such microbial potentials might be connected with the endosymbiotic theory, which states that eukaryotic cells are generated through endosymbiotic relationship between prokaryotes (Woese et al., 1990). In this chapter, we briefly discussed about several evidences of bacterial impact on cellular homeostasis and plasticity. We largely focused on LAB-mediated cell reprogramming of HDF cells as a potential technique for future iPS cells generation.
... As outlined in Fig. 2.1, nanotechnology in biology has wide-spread applications in biomarkers, imaging, diagnostics, therapeutics, and precision medicine. Advances in medical imaging through nanomaterial-based technologies have led to improved results in optical, nuclear, ultrasound, and magnetic resonance imaging (MRI) alike (Caruthers et al., 2007). Some of the earliest advances made use of paramagnetic iron oxide particles to image cancerous tissue in lymph nodes (Weissleder et al., 1990). ...
Chapter
In 2006, Takahashi and Yamanaka reported the generation of mouse and human induced pluripotent stem cells (iPS cells) by retroviral gene transduction of four transcription factors, famously known as Yamanaka factors (OCT4, SOX2, Klf4, and c-Myc) (Takahashi et al., 2007; Takahashi and Yamanaka, 2006). iPS cells show stemness properties (self-renewal and differentiation into three germ layers derivatives) that are comparable to the embryonic stem cells (ES cells). However, conventional iPS cells technique is not entirely safe because of its procedural difficulties, lower efficiency, and the risk of cancer formation (Luo et al., 2013; Rais et al., 2013). Meanwhile, several bacteria-mediated strategies have been identified that can reprogram differentiated cells into stem cell–like state and dedifferentiate into three germ layer derived cells. In 2012, Fuji et al. reported Helicobacter pylori bacteria can reprogram gastric epithelial cells into intestinal stem/progenitor-like cells in vivo by inducing homeobox transcription factors (CDX) during intestinal metaplasia (Fujii et al., 2012). In the same year, our group discovered that lactic acid bacteria (LAB) can reprogram human dermal fibroblast (HDF) into stem cell–like cells in vitro that can differentiate into all three germ layer derivatives (Ohta et al., 2012). Later, Masaki et al. reported that leprosy-causing bacterium Mycobacterium leprae reprograms adult Schwann cells into stem cell–like cells in vivo that differentiate into mesenchymal, skeletal, and smooth muscle cells facilitating infection dissemination (Masaki et al., 2013). In 2017, Ikeda et al. reported that Wolbachia pipientis bacterial proteins can accelerate traditional retroviral-mediated iPS cells generation process (Ikeda et al., 2017). All these studies substantiate the epigenetic potentials of bacteria or its material to induce stemness in differentiated cells. Such microbial potentials might be connected with the endosymbiotic theory, which states that eukaryotic cells are generated through endosymbiotic relationship between prokaryotes (Woese et al., 1990). In this chapter, we briefly discussed about several evidences of bacterial impact on cellular homeostasis and plasticity. We largely focused on LAB-mediated cell reprogramming of HDF cells as a potential technique for future iPS cells generation.
... This review highlights the most important application of such polymeric nanoreactors in several domains including medicine, ecology, biotechnology, and material science and pay attention to the advantages and drawbacks related with them. While in most cases the active components of nanoreactors are enzymes, there are also some examples where the nanostructure itself serves as a template, for example, to produce gold nanoparticles (Caruthers, Wickline, and Lanza 2007;Deraedt et al. 2013). Nanoreactors are able to provide more precise and early diagnostics, can support surgery through fine localization of tumors, decrease side effects while increasing efficiency in drug therapy and show the way to development of new medical devices due to its sensitivity, specificity and rapid response (Ostafin and Chen). ...
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Nanoreactors are a type of chemical reactor that is used mostly in nanotechnology and nanobiotechnology. These unique reactors are critical to the operation of a nano foundry, which is essentially a foundry that produces goods on a nanoscale. Active sites, such as transitional metal species, can also be added to nanoreactors. In this situation, the NR's limited area might impact reaction rate and mechanism by increasing the contacts between reactants and active sites and changing the concentration of the reactant at the active site.
... Generally, nanonization comprising mechanical grinding and the formation of a nanosuspension (Rogers et al., 2003) was previously reported to improve the physicochemical properties and the bioavailability of several drugs (Devalapally et al., 2007). Equally interesting, the use of the nanocarriers approach including the most commonly used nanoparticles (NPs) presents a major tool for biomedical applications, particularly for delivering pharmaceuticals aiming for diagnostic and therapeutic purposes (Caruthers et al., 2007). Different techniques have been used to obtain nanoparticles. ...
Article
Citrus flavonoids are well recognized for their health benefits and contribution to daily nutritional dietary supplements. Their biological effects include anticancer, anti-inflammatory and antioxidant effects. Nevertheless, their low solubility, stability, and bioavailability challenge their potential industrial formulations. This review summarizes the state-of-the art optimization of citrus flavonoid formulations representing the possible physicochemical modifications and their potential implications. These modifications could be achieved using different techniques such as nanonization and encapsulation in nanoscale carriers. This review summarizes the recent research on chemical modifications of citrus flavonoids to facilitate their commercial use and or applications. Applications of these technologies are presented to the reader highlighting their advantages, limitations and needed future improvements. Furthermore, a meta-analysis study was conducted to prove-by-evidence the superiority of drugs-loaded nanocarriers regarding bioavailability compared to their conventionally delivered counterparts.
... Therefore, drug delivery systems have been designed to release drugs in a controlled manner at the desired site to improve their bioavailability and pharmacological properties [2]. To further improve their performance, nanoengineering has been introduced in the pharmaceutical sphere, and its applications are growing rapidly [3]. Nanocarriers have garnered significant interest in the field of nanomedicine [4]. ...
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Thioguanine is an anti-cancer drug used for the treatment of leukemia. However, thioguanine has weak aqueous solubility and low biocompatibility, which limits its performance in the treatment of cancer. In the present work, these inadequacies were targeted using density functional theory-based simulations. Three stable configurations were obtained for the adsorption of thioguanine molecules on the phosphorene surface, with adsorption energies in the range of −76.99 to −38.69 kJ/mol, indicating physisorption of the drug on the phosphorene surface. The calculated bandgap energies of the individual and combined geometries of phosphorene and thioguanine were 0.97 eV, 2.81 eV and 0.91 eV, respectively. Owing to the physisorption of the drug molecule on the phosphorene surface, the bandgap energy of the material had a direct impact on optical conductivity, which was significantly altered. All parameters that determine the potential ability for drug delivery were calculated, such as the dipole moment, chemical hardness, chemical softness, chemical potential, and electrophilicity index. The higher dipole moment (1.74 D) of the phosphorene–thioguanine complex reflects its higher biodegradability, with no adverse physiological effects.
... K. Sharma et al., 2009;Zhao & Stevens, 1998). Silver nanoparticles (AgNPs) have a wide scope of use in various fields like biological sensors (Mingyong et al., 2001), DNA sequencing (Cao et al., 2001), plasmonics (Maier et al., 2001), medical diagnosis (Groneberg et al., 2006), information storage (Sandhu, 2008), climate change (Guobin et al., 2009), biomedical applications (Shelton et al., 2007), infection prevention (Robin et al., 2011), energy generation (Zach et al., 2006), clean-water technology (Richard, 2009), and so on. Synthesis of NPs by chemical method produces a considerable amount of toxic by-products and is not environment-friendly, whereas physical methods are costly and time-consuming. ...
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The biosynthesized silver nanoparticles (AgNPs) have been reported to possess several therapeutic applications. Silver is one of the important metals known for its bioactive properties not only as macromolecule but also as nanoparticle (NP). The current research focused on the eco-friendly synthesis of Talaromyces islandicus VSGF1(Lab code) -mediated AgNPs. The aqueous culture filtrate of T. islandicus VSGF1 was used as a reducing agent. The formation of AgNPs was confirmed by observing the color change from colorless to colloidal earthy-colored and a sharp absorption peak of ultraviolet-visible (UV-vis) spectroscopy at 400 nm. Fourier-transform infrared spectroscopy revealed the involvement of various functional groups for the formation and stabilization of AgNPs. The structure, size, and shape of mycosynthesized AgNPs were identified by X-ray diffraction (XRD), scanning electron microscopy, and atomic force microscopy (AFM) analysis. The XRD analysis exhibited crystalline nature of NPs whereas AFM analysis revealed the spherical shape of AgNP with average size range between 13 and 66 nm. The antibacterial activity of AgNPs (50 μg/ml) investigated against gram-positive and gram-negative bacteria revealed maximum zone of inhibition (ZOI) against drug-resistant Enterococcus faecalis MTCC439 (18.66 ± 0.57 mm) and Pseudomonas aeruginosa MTCC96 (16 ± 0 mm) followed by Staphylococcus aureus MTCC96 (15.33 ± 0.57 mm), Bacillus subtilis MTCC441 (14.66 ± 0.57 mm), and Escherichia coli MTCC45 (14.66 ± 0.57 mm). Further, the AgNPs evaluated for antitumor activity against human hepatocellular carcinoma (HepG2) cell line exhibited promising result with half-maximal inhibitory concentration (MIC) value at 38.17 μg/ml concentration through MTT (methylthiazolyl tetrazolium assay) assay. Apparently, this is the first report from T. islandicus to the best of our knowledge.
... Recently, nanomaterials have received increasing attention in the fields of drug delivery, diagnostics, therapy, medical imaging, and engineering. Nanoparticle systems are used to improve the physicochemical properties and enhance the bioavailability of drugs [10][11][12][13][14]. Mesoporous silica nanoparticle (MSN) drug delivery is a safe candidate for targeted treatment. ...
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Notoginsenoside R1 (NGR1) is the main monomeric component extracted from the dried roots and rhizomes of Panax notoginseng, and exerts pharmacological action against myocardial infarction (MI). Owing to the differences in compound distribution, absorption, and metabolism in vivo, exploring a more effective drug delivery system with a high therapeutic targeting effect is crucial. In the early stages of MI, CD11b-expressing monocytes and neutrophils accumulate at infarct sites. Thus, we designed a mesoporous silica nanoparticle-conjugated CD11b antibody with loaded NGR1 (MSN-NGR1-CD11b antibody), which allowed NGR1 precise targeted delivery to the heart in a noninvasively manner. By increasing targeting to the injured myocardium, intravenous injection of MSN-NGR1-CD11b antibody nanoparticle in MI mice improved cardiac function and angiogenesis, reduced cell apoptosis, and regulate macrophage phenotype and inflammatory factors and chemokines. In order to further explore the mechanism of NGR1 protecting myocardium, cell oxidative stress model and oxygen-glucose deprivation (OGD) model were established. NGR1 protected H9C2 cells and primary cardiomyocytes against oxidative injury induced by H2O2 and OGD treatment. Further network pharmacology and molecular docking analyses suggested that the AKT, MAPK and Hippo signaling pathways were involved in the regulation of NGR1 in myocardial protection. Indeed, NGR1 could elevate the levels of p-Akt and p-ERK, and promote the nuclear translocation of YAP. Furthermore, LY294002 (AKT inhibitor), U0126 (ERK1/2 inhibitor) and Verteporfin (YAP inhibitor) administration in H9C2 cells indicated the involvement of AKT, MAPK and Hippo signaling pathways in NGR1 effects. Meanwhile, MSN-NGR1-CD11b antibody nanoparticles enhanced the activation of AKT and MAPK signaling pathways and the nuclear translocation of YAP at the infarcted site. Our research demonstrated that MSN-NGR1-CD11b antibody nanoparticle injection after MI enhanced the targeting of NGR1 to the infarcted myocardium and improved cardiac function. More importantly, our pioneering research provides a new strategy for targeting drug delivery systems to the ischemic niche.
... A new field of research has been created by the application of nanotechnology to medical research, offering scientists and researchers an entirely new way of studying biological systems. By manipulating materials at the nanometer scale, it is possible to change their fundamental physical characteristics and bioactivity; these tools can provide control over measures such as altered solubility and retention time of the blood pool, controlled release for short or long periods, environmental triggers, or the highly targeted delivery of drugs [16]. Targeted drug delivery would enable the drug to remain stable, absorb, and concentrate more strongly throughout the target tissue and also permit its release at the target site to be reproducible and long-lasting [17,18]. ...
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Engineering, physics, chemistry, and biology are all involved in nanotechnology, which comprises a wide variety of multidisciplinary scientific field devices. The holistic utilization of metallic nanoparticles in the disciplines of bio-engineering and bio-medicine has attracted a great deal of attention. Medical nanotechnology research can offer immense health benefits for humans. While the advantages of developing nanomaterials have been well documented, it is precisely apparent that there are still some major issues that remain unattended to those need to be resolved immediately so as to ensure that they do not adversely affect living organisms in any manner. The existence of nanoparticles gives them particular value in biology and materials science, as an emerging scientific field, with multiple applications in science and technology, especially with numerous frontiers in the development of new materials. Presented here is a review of recent noteworthy developments regarding plant-derived nanomaterials and their use in the development of medicine and biomedical applications around the world.
... It can be defined as the monitoring, repair, construction and control of human biological systems at the molecular level by using engineered nanodevices and Nano structures 47 . The overall goal of nanomedicine is to diagnose accurately and early to treat as effectively as possible with minimum side effects 48 . ...
Article
Nanoparticles are an emerging field of modern science. It is solid colloidal particles. They consist of micro molecular materials in which the active ingredients is dissolved, entrapped or encapsulated or adsorbed or attached. The size of nanoparticles ranges from 1 to 100 nm. It can be synthesized chemically or biologically. Nanoparticles are used in various purposes like in drug delivery, in food, in medicine, in cosmetics etc. There are lots of advantages of nanomedicine over other dosage form. Nanoparticles show high solubility as well as higher bioavailability on site of action. This review focuses on synthesis, biosynthesis, types, application, advantage, disadvantage, limitation of nanoparticle.
... 86 As such, the development of nanoparticle-based platforms has been utilized in multiple biomedical fields, including hydrophobic drug delivery, which undoubtedly provides a promising strategic improvement. 115 Indeed, several natural product-derived anticancer nanodrugs, including nanoparticle albumin-bound (NAB)-paclitaxel and liposomal vincristine, have been used in clinical practice. 21 However, no clinical trials have been reported for nanocomposites of PTL and its structurally related sesquiterpene lactones. ...
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Plant-derived sesquiterpene lactones are promising natural sources for the discovery of anti-cancer drugs. As an extensively studied sesquiterpene lactone, the tumor suppression effect of parthenolide (PTL) has been clarified by targeting a number of prominent signaling pathways and key protein regulators in carcinogenesis. Notably, PTL was also the first small molecule reported to eradicate cancer stem cells. Nevertheless, the clinical application of PTL as an antitumor agent remains limited, owing to some disadvantages such as low water solubility and poor bioavailability. Thus, nanomedicine has attracted much interest because of its great potential for transporting poorly soluble drugs to desired body sites. In view of the significant advantages over their free small-molecule counterparts, nanoparticle delivery systems appear to be a potential solution for addressing the delivery of hydrophobic drugs, including PTL. In this review, we summarized the key anticancer mechanisms underlined by PTL as well as engineered PTL nanoparticles synthesized to date. Therefore, PTL nanoformulations could be an alternative strategy to maximize the therapeutic value of PTL.
... By manipulating drugs and other materials at a nanometer scale, materials' essential properties or bioactivity can be changed. Thus, many factors such as solubility or retention time in the bloodstream, controlled release for short or long periods and target site-specific release can be manipulated [38]. In this study, we have designed a boron-based drug delivery system by integrating an FA functional group into hBN NPs through an esterification reaction. ...
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The search for an innovative and effective drug delivery system that can carry and release targeted drugs with enhanced activity to treat Alzheimer’s disease has received much attention in the last decade. In this study, we first designed a boron-based drug delivery system for effective treatment of AD by integrating the folic acid (FA) functional group into hexagonal boron nitride (hBN) nanoparticles (NPs) through an esterification reaction. The hBN-FA drug carrier system was assembled with a new drug candidate and a novel boron-based hybrid containing an antioxidant as BLA, to constitute a self-assembled AD nano transport system. We performed molecular characterization analyses by using UV-vis spectroscopy, Fourier transform infrared spectrophotometer (FTIR), scanning electron microscope (SEM), Energy-dispersive X-ray spectroscopy (EDS) and Zeta potential investigations. Second, we tested the anti-Alzheimer properties of the carrier system on a differentiated neuroblastoma (SHSY5-Y) cell line, which was exposed to beta-amyloid (1–42) peptides to stimulate an experimental in vitro AD model. Next, we performed cytotoxicity analyses of synthesized molecules on the human dermal fibroblast cell line (HDFa) and the experimental AD model. Cytotoxicity analyses showed that even higher concentrations of the carrier system did not enhance the toxicological outcome in HDFa cells. Drug loading analyses reported that uncoated hBN nano conjugate could not load the BLA, whereas the memantine loading capacity of hBN was 84.3%. On the other hand, memantine and the BLA loading capacity of the hBN-FA construct was found to be 95% and 97.5%, respectively. Finally, we investigated the neuroprotective properties of the nano carrier systems in the experimental AD model. According to the results, 25 µg/mL concentrations of hBN-FA+memantine (94% cell viability) and hBN-FA+BLA (99% cell viability) showed ameliorative properties against beta-amyloid (1–42) peptide toxicity (50% cell viability). These results were generated through the use of flow cytometry, acetylcholinesterase (AChE) and antioxidant assays. In conclusion, the developed drug carrier system for AD treatment showed promising potential for further investigations and enlightened neuroprotective capabilities of boron molecules to treat AD and other neurodegenerative diseases. On the other hand, enzyme activity, systematic toxicity analyses, and animal studies should be performed to understand neuroprotective properties of the designed carrier system comprehensively.
... The composition and design of the dosage form is a compromise between the stringent requirements for the dosage form and the level of development of modern technologies. The requirements for the dosage form depend on the type of disease, the location of the focus of the pathological process, the properties of the active substances, the route of administration of the drug, and the presence of additional requirements[325,326]. To date, the range of dosage forms has not particularly expanded, but varieties with a modified release of active substances (prolonged or accelerated) have appeared. ...
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All rights reserved. Printed in the United States of America. No part of this publication may be reproduced, distributed, or transmitted, in any form or by any means, or stored in a data base or retrieval system, without the prior written permission of the publisher. The content and reliability of the articles are the responsibility of the authors. When using and borrowing materials reference to the publication is required. Collection of scientific articles published is the scientific and practical publication, which contains scientific articles of students, graduate students, Candidates and Doctors of Sciences, research workers and practitioners from Europe and Ukraine. The articles contain the study, reflecting the processes and changes in the structure of modern science.
... The composition and design of the dosage form is a compromise between the stringent requirements for the dosage form and the level of development of modern technologies. The requirements for the dosage form depend on the type of disease, the location of the focus of the pathological process, the properties of the active substances, the route of administration of the drug, and the presence of additional requirements[325,326]. To date, the range of dosage forms has not particularly expanded, but varieties with a modified release of active substances (prolonged or accelerated) have appeared. ...
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З’єднання анатомічних структур або вісцеральних (внутрішніх) органів має вирішальне значення в хірургії. З’єднання тканин – найбільш актуальна проблема хірургії. Відновлення цілісності пошкоджених органів та тканин становило основу хірургії з її зародження. Травми, ушкодження при патологічних процесах, оперативних втручаннях – всі ці ситуації вимагають хірургічного втручання, в основі якого лежить з'єднання тканин, тобто накладання швів.
Preprint
In this work, we have investigated the possibility of using COOH functionalized CdTe quantum dots (QDs) as fluorescent nanosensor for the detection of some environmentally hazardous metal ions ($\rm{Cr^{3+}}$, $\rm{Pb^{2+}}$, $\rm{Cu^{2+}}$, $\rm{Zn^{2+}}$ and $\rm{Co^{2+}}$) in aqueous phase. COOH-CdTe QDs are prepared in aqueous medium and characterized by UV-visible, photo luminescence and FTIR spectrometry. Optical response of CdTe nanosensor is observed to be time and temperature dependent. A strong "Turn-Off" fluorescence response of CdTe is observed in presence of all metals ions ($\rm{X^{n+}}$). The output of Stern volmer relation, graphical Job's plot and FTIR data established the existence of strong 1:1 complexation ($\rm{X^{n+}: ^{-}OOC-CdTe)}$ between CdTe and metal ions. CdTe shows its efficient sensing ability for $\rm{Pb^{2+}}$, $\rm{Cr^{3+}}$ and $\rm{Cu^{2+}}$ ions up to concentration $\rm{10^{-14}}$ M which was established by its low detection of limit (LOD)validation. Further, strong appearance of $\frac{F-F_{0}}{F_{0}}$ establishes the better sensing capability of CdTe QDs for $\rm{Cr^{3+}}$, $\rm{Pb^{2+}}$, $\rm{Cu^{2+}}$ ions which are far better than the existing fluorescent sensors available in industry. The proposed optical techniques and principal component analysis of sensing were successfully applied for testing of dissolved metal ions in real samples like: paint, river water, rain water etc which validates the applicability of COOH functionalized CdTe nanosensor as a effective successful optical sensor for water dissolved metal ions which are responsible for water pollution.
Article
In this work, we have investigated the possibility of using COOH functionalized CdTe quantum dots (QDs) as fluorescent nanosensor for the detection of some environmentally hazardous metal ions (Cr³⁺, Pb²⁺, Cu²⁺, Zn²⁺ and Co²⁺) in aqueous phase. COOH–CdTe QDs are prepared in aqueous medium and characterized by UV–visible, photo luminescence and FTIR spectrometry. Optical response of CdTe nanosensor is observed to be time and temperature dependent. A strong “Turn-Off” fluorescence response of CdTe is observed in presence of all metals ions (Xⁿ⁺). The output of Stern volmer relation, graphical Job's plot and FTIR data established the existence of strong 1:1 complexation (Xⁿ⁺: OOC-CdTe) between CdTe and metal ions. CdTe shows its efficient sensing ability for Pb²⁺, Cr³⁺ and Cu²⁺ ions up to concentration 10⁻¹⁴ M which was established by its low detection of limit (LOD)validation. Further, strong appearance of F–F0/F0 establishes the better sensing capability of CdTe QDs for Cr³⁺, Pb²⁺, Cu²⁺ ions which are far better than the existing fluorescent sensors available in industry. The proposed optical techniques and principal component analysis of sensing were successfully applied for testing of dissolved metal ions in real samples like: paint, river water, rain water etc which validates the applicability of COOH functionalized CdTe nanosensor as an effective successful optical sensor for water dissolved metal ions which are responsible for water pollution.
Book
Biogenic Nanoparticles for Cancer Theranostics outlines the synthesis of biogenic nanoparticles to become cancer theranostic agents. The book also discusses their cellular interaction and uptake, pharmacokinetics, biodistribution, drug delivery efficiency, and other biological effects. Additionally, the book explores the mechanism of their penetration in cancerous tissue, its clearance, and its metabolism. Moreover, the in vitro and in vivo toxicological effects of biogenic nanoparticles are discussed. This book is an important reference source for materials scientists and biomedical scientists who are looking to increase their understanding of how biogenic nanoparticles are being used for a range of cancer treatment types. Metal nanoparticles have traditionally been synthesized by classical physico-chemical methods which have many drawbacks, such as high energy demand, high cost and potential ecotoxicity. As a result, the biosynthesis of metal nanoparticles is gaining increasing prominence. Biosynthesis approaches to metal nanoparticles are clean, safe, energy efficient and environment friendly.
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Agricultural Biotechnology
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Nanotechnology has been widely applied to medical interventions for prevention, diagnostics, and therapeutics of diseases, and the application of nanotechnology for medical purposes, which is called as a term “nanomedicine” has received tremendous attention. In particular, the design and development of nanoparticle for biosensors have received a great deal of attention, since those are most impactful area of clinical translation showing potential breakthrough in early diagnosis of diseases such as cancers and infections. For example, the nanoparticles that have intrinsic unique features such as magnetic responsive characteristics or photoluminescence can be utilized for noninvasive visualization of inner body. Drug delivery that makes use of drug-containing nanoparticles as a carrier is another field of study, in which the particulate form nanomedicine is given by parenteral administration for further systemic targeting to pathological tissues. In addition, encapsulation into nanoparticles gives the opportunity to secure the sensitive therapeutic payloads that are readily degraded or deactivated until reached to the target in biological environments, or to provide sufficient solubilization (e.g., to deliver compounds which have physicochemical properties that strongly limit their aqueous solubility and therefore systemic bioavailability). The nanomedicine is further intended to enhance the targeting index such as increased specificity and reduced false binding, thus improve the diagnostic and therapeutic performances. In this chapter, principles of nanomaterials for medicine will be thoroughly covered with applications for imaging-based diagnostics and therapeutics.
Chapter
Since emergence of the concept of nanotechnology, a plethora of nanomaterials have been designed and evaluated for their potential role in biomedical applications. Among the synthesis strategies like chemical synthesis, biological synthesis, or physical synthesis, nanoparticles formed by biological synthesis process, have attracted a lot of attention for their non-toxic and eco-friendly nature. Over the years, these biologically synthesized or green-synthesized nanoparticles (GSN) have been explored for their roles in biomedicine. Recent studies unveiled that these GSNs possess important intrinsic properties including high fluorescence, noninvasiveness, high sensitivity, long-half life, target-specific binding via chemical functionalization, etc. Thus, these green-synthesized fluorescent nanoparticles (GSFNs) can be used as alternatives to the conventionally used fluorescent dyes for bio-imaging. In this book chapter, we have shed a light on the potential in vitro and in vivo applications of recently published GSFNs in bio-imaging as well as the challenges associated with their employment in patient diagnosis.
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The CRISPR/Cas system was first discovered as a defense mechanism in bacteria and is now used as a tool for precise gene-editing applications. Rapidly evolving, it is increasingly applied in therapeutics. However, concerns about safety, specificity, and delivery still limit its potential. In this context, we introduce the concept of nanogenetics and speculate how the rational engineering of the CRISPR/Cas machinery could advance the biomedical field. In nanogenetics, the advantages of traditional approaches of synthetic biology could be expanded by nanotechnology approaches, enabling the design of a new generation of intrinsically safe and specific genome-editing platforms.
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Engineered nanomaterial manufacturing and utilization has been increasing in both consumer and commercial products. As stated by the Project on Emerging Nanotechnologies, there are 1814 nanotechnology consumer products available in the market as of Mach 2015. In Project on Emerging Nanotechnologies’ consumer product inventory list, nanoproducts are categorized into eight main categories; house appliances, automotive, cross-cutting, electronics and computers, food and beverage, goods for children, health, and fitness, and home and garden. Nanomaterials provide numerous advantages over conventional materials, even though their small size, shape and related properties may likewise expand their toxicity levels. The bioaccumulation of nanomaterials begins with nanoparticle accumulation in the organism, and then biomagnification follows the toxins accumulated by the predatory organism. Bioconcentration is the last stage, whereby the chemical concentration of toxins in the organism exceeds that in the environment. Here, we have reviewed the interaction of nanomaterials with biological substances focusing on bioaccumulation, biomagnification, and bioconcentration, in order to determine the effect of each nanomaterial on the microorganism as well as the environment from beginning to end. It has been observed that the effects of nanomaterials begin at the bottom of the food chain and move all the way through the human body.
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In this research, Argon gas was used to generate atmospheric plasma in the manufacture of platinum nanomaterials, to study the resultant plasma spectrum and to calculate the cellular toxicity of those manufactured nanomaterials. This research is keen on the generation of nonthermal atmospheric pressure plasma using aqueous platinum salts (H 2 PtCl 6 6H 2 O) with different concentrations and exposure of cold plasma with a different time period used to produce platinum nanoparticles, to ensure typical preparation of nanoparticles. Visible UV and X-rays were performed for this purpose, and the diameter of the system probe was (1[Formula: see text]mm) with the Argon gas flow of 2.5[Formula: see text]min/L to prepare the platinum nanoparticles, and spectroscopic study of plasma parameter including, electron temperature, electron density, Debye length and plasma frequency, were computed using spectral analysis techniques. The effect of nanoparticles on natural lymphocytes was studied to calculate cytotoxicity and the greatest proportion was at the concentration of 100% nanoparticle platinum is 37.4%. The study results revealed that cold in the atmosphere is a promising technology when used in the production of nanoparticle materials which can be used for many industrial and medical applications.
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Solid lipid nanoparticles are one of the developed technologies for addressing the bioavailability and targeting issues of drug delivery. In this review article, we attempted to incorporate all the essential details of SLNs like various methods of preparation, different models of SLNs, updated characterization methods, in-vivo behavior (Uptake), their applications, route of administration as well as advancements taken place in the field of delivery of biological drugs like gene vector, new adjuvant for vaccines, protein, and peptide with SLNs. Surface modified SLNs hold excellent potential for targeted and controlled drug delivery which is discussed and summarized. Based on the available data, the future success of SLNs is widened because they could be easily fabricated with various functionalities which would display enormous potential for targeting and diagnosing various diseases. This review would help the budding researchers to find out the unexplored areas of SLNs with the present discussion that reframes the potential of SLNs by gathering the various research findings of SLNs in tabular form along with the approved patent technologies of SLNs.
Chapter
Nanotechnology has revolutionized fields from astrophysics to biology over the past two decades. Increasingly, nanoparticles have been used in biomedical research and medicine as powerful tools for transgene and drug delivery, imaging, diagnostics, and therapeutics. Induced pluripotent stem cells (iPSCs) and human iPSCs (hiPSCs)-derived cells have the potential to revolutionize the regenerative, therapeutic, and precision medicine. Genetic modification of iPSCs represents an essential tool for the study and application of iPSCs. However, there are significant technical challenges for transgene delivery into iPSCs since these cells are known to be difficult for transfection. The existing transgenic methods, such as viral transduction and chemical transfection, may introduce significant alternations during iPSC culture which affect the potency, purity, consistency, and functional capacity of iPSCs. Magnetic nanoparticles have the potential to facilitate the magnetic field–guided transgene delivery to the iPSCs and offer a simple and robust approach for transgene delivery to iPSCs. Magnetic nanoparticle–mediated gene transfer offers significant advantages over other gene transfer methods, such as high efficiency, low cytotoxicity and biodegradability, low cost, directional and distal controllability, efficient in vivo applications, and lack of immune responses. This chapter discusses the principles and applications of magnetic nanoparticles in the transgene delivery to iPSCs.
Article
Investigation of the interactions between pyridine derivatives and model compounds of protein, as dipeptides and oligopeptides, is of special interest for pharmaceutical applications. Studies on physicochemical properties of their aqueous solutions play key role in understanding the nature of molecular interactions in liquid mixtures. Here the calorimetric method was used to measure the enthalpy of mixing in aqueous solutions of the dipeptide L-carnosine with the drug isonicotinic acid. The data were analyzed based on the McMillan–Mayer theory to obtain the cross-pair interaction coefficient, hxy, that indicates relatively strong interactions with predominant hydrophilic specific interactions.
Chapter
Several studies on the application of magnetic nanoparticles are vast covering synthesis, functionalization in vitro and in vivo trials, not to mention. In this chapter, we attempt to discuss key areas in their biomedical applications with focus on hyperthermia treatment for cancer therapy. To assure a comprehensive understanding, related topics may be discussed at different sections of the chapter. Semimodern use of magnetic nanoparticles in hyperthermia is it tracked back to the 1950s. Since then, frequently employed magnetic nanoparticles are elaborated to their corresponding nature as free, alloyed, coated, and functionalized materials. Various synthesis methods with their pros and cons and including their major experimental procedures are mentioned and compiled into physical, biological, and chemical methods. In analyzing data, key parameters such as hysteresis loss, Neel and Brownian relaxation are used to justify the suitability of the materials for such application and their meanings and interpretations are precisely described here. All these inputs will either contribute to analytic aspect or therapeutic application in hyperthermia technique. This biomedical technique can be directed targeting tumor cells in a specific organ or for the whole body.
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A novel optical aptasensor with excellent sensitivity and high selectivity was fabricated as a tool for insulin determination in human blood plasma. The performance of the probe is based on surface energy transfer (SET) between thioglycolic acid capped indium phosphide/zinc sulfide quantum dots (TGA-InP/ZnS QDs) (donor) and Ag-nanoplates (acceptor). Initially, low-risk TGA-InP/ZnS core-shell QDs with high fluorescence quantum yield (ФF =73%) were synthesized via the stepwise method. Ag-nanoplates with well surface plasmon resonance (SPR), high extinction coefficient, viability, good optical and chemical stability act as fluorescence signal quencher. Insulin aptamer strands (Ap) was used as the biorecognition element and linked to the QDs surface by the covalent bonds (Ap-QDs). In the absence of insulin, Ap-QDs are adsorbed on the Ag-nanoplates surface and fluorescence intensity quenched. By adding insulin to the media, due to the high aptamer affinity to the insulin, AP-QDs getting away from Ag-nanoplates and the fluorescence signal of QDs was restored related to the insulin quantity. In the optimized situations probe works in the dynamic range (DR) (0.001-5000 nM) with a limit of detection (LOD = 0.5 pM). This method was used to measure insulin in blood plasma and its accuracy was estimated by comparison obtained results with the standard method (HPLC).
Article
Lung cancer (LC) is often diagnosed at an advanced stage and conventional treatments for disease management have limitations associated with them. Novel therapeutic targets are thus avidly sought for the effective management of LC. RNA binding proteins (RBPs) have been convincingly established as key players in tumorigenesis, and their dysregulation is linked to multiple cancers, including LC. In this context, we review the role of Human antigen R (HuR), an RBP that is overexpressed in LC, and further associated with various aspects of LC tumor growth and response to therapy. Herein, we describe the role of HuR in LC progression and outline the evidences supporting various pharmacologic and biologic approaches for inhibiting HuR expression and function. These approaches, including use of small molecule inhibitors, siRNAs and shRNAs, have demonstrated favorable results in reducing tumor cell growth, invasion and migration, angiogenesis and metastasis. Hence, HuR has significant potential as a key therapeutic target in LC. Use of siRNA-based approaches, however, have certain limitations that prevent their maximal exploitation as cancer therapies. To address this, in the conclusion of this review, we provide a list of nanomedicine-based HuR targeting approaches currently being employed for siRNA and shRNA delivery, and provide a rationale for the immense potential therapeutic benefits offered by nanocarrier-based HuR targeting and its promise for treating patients with LC.
Chapter
Poor bioavailability (BA) has become a major issue in the drug discovery in pharmaceutical industry as majority of the new molecules have poor water solubility. Hydrophilic milieu of the gastrointestinal tract (GIT) restricts the absorption of such lipophilic entities. Most of the drugs are directly absorbed through the portal vein after oral administration but there are several lipophilic molecules which enter into the systemic circulation by lymphatic transport. Additionally, this characteristic also hinders the development of successful delivery system. Pharmacokinetic property of drugs is also affected by presence of food as it causes delay in gastric emptying, promote gastric motility, promote bile salt secretion, etc. Nanoparticles are considered as an effective approach to overcome hurdles and the pharmacokinetic and pharmacodynamic limitations linked with such lipophilic molecules. Lipid-based nanoparticles like solid lipid nanoparticles, nanostructured lipid carriers, self-microemulsifying drug delivery system, liposomes, etc. have gained more attention for delivery of lipophilic molecules. The pharmaceutical industries are looking for another path for delivery of drugs to evade issues related with poor bioavailability. Currently for orally administered lipophilic drugs, the intestinal lymphatic system (ILS) has become an absorptive pathway to conquer such limitations, which can avoid liver-assisted first-pass metabolism and aid bioavailability. The ILS is a path which transports fat-soluble vitamins, food-derived lipids, and lipophilic peptides to systemic circulation. This chapter emphasizes on the ILS, the role of the lymphatic system in bioavailability enhancement, and application of nanoparticles for improving BA via this route.KeywordsBioavailabilityIntestinal lymphatic systemNanoparticlesOral delivery
Article
We present the synthesis of amorphous, mesoporous, colloidal magnesium phosphate-citrate nanoparticles (MPCs) from biogenic precursors, resulting in a biocompatible and biodegradable nanocarrier that amplifies the action of the anticancer drug methotrexate (MTX). Synthesis conditions were gradually tuned to investigate the influence of the chelating agent citric acid on the colloidal stability and the mesoporosity of the obtained nanoparticles. With optimized synthesis conditions, a large BET surface area of 560 m2/g was achieved. We demonstrate the potential of these biocompatible and biodegradable mesoporous MPCs as a drug delivery system. Lipid-coated MPCs were used to load the fluorescent dye calcein and the chemotherapeutic agent MTX into the mesopores. In vitro experiments show very low premature release of the cargo but efficient stimuli-responsive release in an environment of pH 5.5, in which MPCs degrade. Lipid-coated MPCs are taken up by cancer cells and are nontoxic up to concentrations of 100 μg/mL. When loaded with MTX serving as a representative model drug for in vitro studies, MPCs induced efficient cell death with an IC50 value of 1.1 μg/mL. Compared to free MTX, its delivery with MPCs enhances its efficiency by an order of magnitude. In summary, we have developed a biodegradable nanomaterial synthesized from biocompatible precursors that are neither toxic by themselves nor in the form of nanoparticles. With these features, MPCs may be applied as drug delivery systems and have the potential to reduce the side effects of current chemotherapies.
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Silver nanoparticles has gain great attention in the research field in the recent years. It is due to their size, eco-friendly, cost effective, chemical stability, availability, biocompatibility, antimicrobial activity, antiviral activity, anticancer activity and many more therapeutic applications. Especially the green synthesis of nanoparticles has been most popular due to their high efficiency, non-pollutant and cost effective approach which helps in stabilizing the silver nanoparticles for vast applications. Their therapeutic applications have got a great advantage in the field due to the potential usage of phytochemicals in order to reduce and use them as antimicrobial and anticancer agents. This review provides an insight into the plant mediated synthesis of nanoparticles, methods of plant extract preparation, stabilization and characterization of nanoparticles, antibacterial and anticancer activities followed by their applications.
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The aim of this study is to fabricate a new scaffold appropriate for tissue regeneration with antimicrobial activity and ability of controlled drug delivery. In this regard, scaffold nanofibers were produced using poly (methyl methacrylate) (PMMA), Mo132 as a Keplerate polyoxometalate and metronidazole. The final scaffolds, obtained by electrospinning, represent the intrinsic features including exceptional doubling tensile strength, high hydrophilicity (126 ± 5.2° to 83.9 ± 3.2° for contact angle and 14.18 ± 0.62% to 35.62 ± 0.24% for water uptake), proper bioactivity and cell adhesion. Moreover, the addition of Mo132 and metronidazole enhances the biodegradation rate of resulted scaffolds compared to the pure PMMA membrane. The controlled release of metronidazole over 14 days efficiently inhibits the colonization of anaerobic microorganisms. Overall, the results demonstrate high potential of Mo132 and metronidazole-loaded PMMA scaffold for guided bone regeneration/guided tissue regeneration.
Conference Paper
Squamous cell carcinoma (SCC) is the most commonly diagnosed oral cancer. It is a type of head and neck squamous cell carcinoma (HNSCC) oral cancer affects more than 300,000 people in a year. Oral cancer is the sixth most common malignant cancer. The traditional methods of treatment were used through surgery, followed by chemotherapy, but these methods are not effective enough for the treatment, so treatment was focused on using magnetic nanoparticles. Magnetic nanoparticles demolish only the cancer cells directly without affecting healthy cells. They can also be used to increase the effectiveness of the other treatment methods. Iron oxide nanoparticles, maghemite (Fe2O3) and magnetite (Fe3O4) are widely used in the diagnosis and treatment of cancerous diseases. Iron oxides NPs have distinctive properties as they have good biodegradability, very low toxicity, modifiability, and ease of preparation. the method of hyperthermia is one of the effective methods in the treatment of cancer. Because cancer cells show greater sensitivity to high temperature compared to normal cells.
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Much previous work in methods of achieving complex drug-release patterns has focused on pulsatile release from polymeric materials in response to specific stimuli, such as electric or magnetic fields, exposure to ultrasound, light or enzymes, and changes in pH or temperature. An alternative method for achieving pulsatile release involves using microfabrication technology to develop active devices that incorporate micrometre-scale pumps, valves and flow channels to deliver liquid solutions. Here we report a solid-state silicon microchip that can provide controlled release of single or multiple chemical substances on demand. The release mechanism is based on the electrochemical dissolution of thin anode membranes covering microreservoirs filled with chemicals in solid, liquid or gel form. We have conducted proof-of-principle release studies with a prototype microchip using gold and saline solution as a model electrode material and release medium, and we have demonstrated controlled, pulsatile release of chemical substances with this device.
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In this review, the different types of liposome used in medicine, in particular in the field of antitumor therapy, are focalised, emphasizing their structures, pharmacological action, pharmacokinetics and biodistribution, toxicity profiles and in the main clinical applications. The first-generation liposomes (conventional liposomes) comprised a liposome-containing amphotericin B, Ambisome, and Myocet, doxorubicin-containing liposome used in clinical trials to treat metastatic breast cancer. The last generation liposomes were pegylated liposomal doxorubicin (Caelix), called "stealth liposomes" because of their ability to evade interception by the immune system, characterized by very long-circulation half-life, favourable pharmacokinetic behaviour and specific accumulation in tumor tissues.
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In oncological research, there is a great need for imaging techniques that specifically identify angiogenic blood vessels in tumors on the basis of differences in the expression level of biomolecular markers. In the angiogenic cascade, different cell surface receptors, including the alphavbeta3-integrin, are strongly expressed on activated endothelial cells. In the present study, we aimed to image angiogenesis by detecting the expression of alphavbeta3 in tumor bearing mice with a combination of magnetic resonance imaging (MRI) and fluorescence microscopy. To that end, we prepared MR-detectable and fluorescent liposomes, which carry approximately 700 alphavbeta3-specific RGD peptides per liposome. RGD competition experiments and RAD-conjugated liposomes were used as controls for specificity. In vivo, both RAD liposomes and RGD liposomes gave rise to signal increase on T1-weighted MR images. It was established by the use of ex vivo fluorescence microscopy that RGD liposomes and RAD liposomes accumulated in the tumor by different mechanisms. RGD liposomes were specifically associated with activated tumor endothelium, while RAD liposomes were located in the extravascular compartment. This study demonstrates that MR molecular imaging of angiogenesis is feasible by using a targeted contrast agent specific for the alphavbeta3-integrin, and that the multimodality imaging approach gave insight into the exact mechanism of accumulation in the tumor.
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Liposomes are spherical lipid bilayers from 50 nm to 1000 nm in diameter that serve as convenient delivery vehicles for biologically active compounds. The field of liposome research has expanded considerably over the last 30 years. It is now possible to engineer a wide range of liposomes varying in size, phospholipid composition and surface characteristics to suit the specific application for which they are intended. This paper gives an overview of the main advances in liposome research from a point of view of their applications in medicine. Aqueous contrast enhancing agents entrapped in liposomal carriers can be targeted to the liver and spleen and distinctions can be made between normal and tumorous tissue using computed tomography. Topical application of liposomes has great potential in dermatology. Liposomes have been used to deliver anticancer agents in order to reduce the toxic effects of the drugs when given alone or to increase the circulation time and effectiveness of the drugs. From the original concept of encapsulating hemoglobin in an inert shell, liposome-encapsulated hemoglobin (LEH) has evolved into a fluid proven to carry oxygen, capable of surviving for reasonable periods in the circulation and amenable to large-scale production. Liposomes may be used to target specific cells by attaching amino acid fragments such as antibodies or proteins or appropriate fragments that target specific receptor sites. Liposomal DNA delivery vectors and further enhancements in the forms of LPDI and LPDII are some of the safest and potentially most versatile transfer vectors used to date. DNA vaccination and improved efficiency of gene therapy are just a few of the upcoming applications of liposomes.
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Targeted contrast agents are expanding the detectability and diagnosis of pathology from a strict anatomic to biochemical basis. Moreover, these new agents, in their various forms, offer the potential for site-specific drug and gene delivery, ie, the "magic bullet" first postulated by Paul Erhlich 100 years ago. The ability to direct drugs to the molecular signatures of disease, to confirm noninvasively their presence at the site-of-interest, and to quantify the adequacy of local drug concentration at the time of treatment, ie, rational targeted drug delivery, offers exciting new clinical paradigms in the near future.
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Laser- and sensitive charge-coupled device technology together with advanced mathematical modelling of photon propagation in tissue has prompted the development of novel optical imaging technologies. Fast surface-weighted imaging modalities, such as fluorescence reflectance imaging (FRI) and 3D quantitative fluorescence-mediated tomography have now become available [1, 2]. These technical advances are paralleled by a rapid development of a whole range of new optical contrasting strategies, which are designed to generate molecular contrast within a living organism. The combination of both, technical advances of light detection and the refinement of optical contrast media, finally yields a new spectrum of tools for in vivo molecular diagnostics. Whereas the technical aspects of optical imaging are covered in more detail in a previous review article in "European Radiology" [3], this article focuses on new developments in optical contrasting strategies and design of optical contrast agents for in vivo diagnostics.
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The recent emergence of “molecular imaging” as an integrated discipline in academic medical centers has set the stage for an evolutionary leap in diagnostic imaging and therapy. 1 Molecular imaging is not a substitute for the traditional process of image formation and interpretation, but is intended to improve diagnostic accuracy and sensitivity by providing an in vivo analog of immunocytochemistry or in situ hybridization. It is less concerned with native image contrast or resolution, which are keys for depicting the effects of the disease on surrounding normal tissues, but rather, it seeks to enhance the conspicuity of microscopic pathologies by targeting the molecular components or processes that represent actual mechanisms of disease. Moreover, imaging will become crucial for in vivo characterization of the complex behaviors of disease in time and space that will tell us: where it is, how big it is, how fast it is developing, how many molecular processes are contributing simultaneously, what to treat it with, how it is responding to therapy, and how it is changing. Elements fundamental to the growth of molecular imaging are exemplified in summary statements from the second Biomedical Imaging Symposium: Visualizing the Future of Biology and Medicine (Available at: http://www.becon1. nih.gov/symposium1999.htm), which convened at the National Institutes for Health (NIH) on June 25 and 26, 1999, and was cosponsored by the Biomedical Engineering Consortium (BECON), the Radiological Society of North America, and the American Institute of Medical and Biological Engineering. The goals of the Symposium were to: (1) “identify the most important challenges and opportunities in biomedical imaging science,” and (2) “develop strategies for integrating imaging science with biological and medical research.” The formation of the BECON was followed by a Congressional mandate to establish a new National Institute for Biomedical Imaging and Bioengineering devoted to the development of novel technologies, including molecular imaging and therapeutics, without the traditional restrictions of hypothesis-driven research. The BECON symposium identified 5 action items critical to achieving these goals: ● Implementation of multidisciplinary research programs, especially in the area of molecular imaging or image guided therapy; ● Development of new imaging technologies, probes, and
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Microfabrication techniques which permit the creation of therapeutic delivery systems that possess a combination of structural, mechanical, and perhaps electronic features may surmount challenges associated with conventional delivery of therapy. In this review, delivery concepts are presented which capitalize on the strengths of microfabrication. Possible applications include micromachined silicon membranes to create implantable biocapsules for the immunoisolation of pancreatic islet cells-as a possible treatment for diabetes-and sustained release of injectable drugs needed over long time periods. Asymmetrical, drug-loaded microfabricated particles with specific ligands linked to the surface are proposed for improving oral bioavailability of peptide (and perhaps protein) drugs. In addition, microfabricated drug delivery systems ranging from transdermal microneedles to implantable microchips will be discussed.
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Nanotechnology extends the limits of molecular diagnostics to the nanoscale. Nanotechnology-on-a-chip is one more dimension of microfluidic/lab-on-a-chip technology. Biological tests measuring the presence or activity of selected substances become quicker, more sensitive and more flexible when certain nanoscale particles are put to work as tags or labels. Magnetic nanoparticles, bound to a suitable antibody, are used to label specific molecules, structures or microorganisms. Magnetic immunoassay techniques have been developed in which the magnetic field generated by the magnetically labeled targets is detected directly with a sensitive magnetometer. Gold nanoparticles tagged with short segments of DNA can be used for detection of genetic sequence in a sample. Multicolor optical coding for biological assays has been achieved by embedding different-sized quantum dots into polymeric microbeads. Nanopore technology for analysis of nucleic acids converts strings of nucleotides directly into electronic signatures. DNA nanomachines can function as biomolecular detectors for homogeneous assays. Nanobarcodes, submicrometer metallic barcodes with striping patterns prepared by sequential electrochemical depositon of metal, show differential reflectivity of adjacent stripes enabling identification of the striping patterns by conventional light microscopy. All this has applications in population diagnostics and in point-of-care hand-held devices.
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A novel nanoparticle-based drug carrier for photodynamic therapy is reported which can provide stable aqueous dispersion of hydrophobic photosensitizers, yet preserve the key step of photogeneration of singlet oxygen, necessary for photodynamic action. A multidisciplinary approach is utilized which involves (i) nanochemistry in micellar cavity to produce these carriers, (ii) spectroscopy to confirm singlet oxygen production, and (iii) in vitro studies using tumor cells to investigate drug-carrier uptake and destruction of cancer cells by photodynamic action. Ultrafine organically modified silica-based nanoparticles (diameter approximately 30 nm), entrapping water-insoluble photosensitizing anticancer drug 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide, have been synthesized in the nonpolar core of micelles by hydrolysis of triethoxyvinylsilane. The resulting drug-doped nanoparticles are spherical, highly monodispersed, and stable in aqueous system. The entrapped drug is more fluorescent in aqueous medium than the free drug, permitting use of fluorescence bioimaging studies. Irradiation of the photosensitizing drug entrapped in nanoparticles with light of suitable wavelength results in efficient generation of singlet oxygen, which is made possible by the inherent porosity of the nanoparticles. In vitro studies have demonstrated the active uptake of drug-doped nanoparticles into the cytosol of tumor cells. Significant damage to such impregnated tumor cells was observed upon irradiation with light of wavelength 650 nm. Thus, the potential of using ceramic-based nanoparticles as drug carriers for photodynamic therapy has been demonstrated.
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Early noninvasive detection and characterization of solid tumors and their supporting neovasculature is a fundamental prerequisite for effective therapeutic intervention, particularly antiangiogenic treatment regimens. Emerging molecular imaging techniques now allow recognition of early biochemical, physiological, and anatomical changes before manifestation of gross pathological changes. Although new tumor, vascular, extracellular matrix, and lymphatic biomarkers continue to be discovered, the alpha(nu)beta(3)-integrin remains an attractive biochemical epitope that is highly expressed on activated neovascular endothelial cells and essentially absent on mature quiescent cells. In this study, we report the first in vivo use of a magnetic resonance (MR) molecular imaging nanoparticle to sensitively detect and spatially characterize neovascularity induced by implantation of the rabbit Vx-2 tumor using a common clinical field strength (1.5T). New Zealand White rabbits (2 kg) 12 days after implantation of fresh Vx-2 tumors (2 x 2 x 2 mm(3)) were randomized into one of three treatment groups: (a) alpha(nu)beta(3)-targeted, paramagnetic formulation; (b) nontargeted, paramagnetic formulation; and (c) alpha(nu)beta(3)-targeted nonparamagnetic nanoparticles followed by (2 h) the alpha(nu)beta(3)-targeted, paramagnetic formulation to competitively block magnetic resonance imaging (MRI) signal enhancement. After i.v. systemic injection (0.5 ml of nanoparticles/kg), dynamic T(1)-weighted MRI was used to spatially and temporally determine nanoparticle deposition in the tumor and adjacent tissues, including skeletal muscle. At 2-h postinjection, alpha(nu)beta(3)-targeted paramagnetic nanoparticles increased MRI signal by 126% in asymmetrically distributed regions primarily in the periphery of the tumor. Similar increases in MR contrast were also observed within the walls of some vessels proximate to the tumor. Despite their relatively large size, nanoparticles penetrated into the leaky tumor neovasculature but did not appreciably migrate into the interstitium, leading to a 56% increase in MR signal at 2 h. Pretargeting of the alpha(nu)beta(3)-integrin with nonparamagnetic nanoparticles competitively blocked the specific binding of alpha(nu)beta(3)-targeted paramagnetic nanoparticles, decreasing the MR signal enhancement (50%) to a level attributable to local extravasation. The MR signal of adjacent hindlimb muscle or contralateral control tissues was unchanged by either the alpha(nu)beta(3)-targeted or control paramagnetic agents. Immunohistochemistry of alpha(nu)beta(3)-integrin corroborated the extent and asymmetric distribution of neovascularity observed by MRI. These studies demonstrate the potential of this targeted molecular imaging agent to detect and characterize (both biochemically and morphologically) early angiogenesis induced by minute solid tumors with a clinical 1.5 Tesla MRI scanner, facilitating the localization of nascent cancers or metastases, as well as providing tools to phenotypically categorize and segment patient populations for therapy and to longitudinally follow the effectiveness of antitumor treatment regimens.
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Angiogenesis is a critical feature of plaque development in atherosclerosis and might play a key role in both the initiation and later rupture of plaques that lead to myocardial infarction and stroke. The precursory molecular or cellular events that initiate plaque growth and that ultimately contribute to plaque instability, however, cannot be detected directly with any current diagnostic modality. Atherosclerosis was induced in New Zealand White rabbits fed 1% cholesterol for approximately 80 days. alpha(v)beta3-Integrin-targeted, paramagnetic nanoparticles were injected intravenously and provided specific detection of the neovasculature within 2 hours by routine magnetic resonance imaging (MRI) at a clinically relevant field strength (1.5 T). Increased angiogenesis was detected as a 47+/-5% enhancement in MRI signal averaged throughout the abdominal aortic wall among rabbits that received alpha(v)beta3-targeted, paramagnetic nanoparticles. Pretreatment of atherosclerotic rabbits with alpha(v)beta3-targeted, nonparamagnetic nanoparticles competitively blocked specific contrast enhancement of the alpha(v)beta3-targeted paramagnetic agent. MRI revealed a pattern of increased alpha(v)beta3-integrin distribution within the atherosclerotic wall that was spatially heterogeneous along both transverse and longitudinal planes of the abdominal aorta. Histology and immunohistochemistry confirmed marked proliferation of angiogenic vessels within the aortic adventitia, coincident with prominent, neointimal proliferation among cholesterol-fed, atherosclerotic rabbits in comparison with sparse incidence of neovasculature in the control animals. This molecular imaging approach might provide a method for defining the burden and evolution of atherosclerosis in susceptible individuals as well as responsiveness of individual patients to antiatherosclerotic therapies.
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Imaging specific molecules and their interactions in space and time will be essential to understand how genomes create cells, how cells constitute organisms and how errant cells cause disease. Molecular imaging must be extended and applied from nanometre to metre scales and from milliseconds to days. This quest will require input from physics, chemistry, and the genetics and biochemistry of diverse organisms with useful talents.
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Unstable atherosclerotic plaques exhibit microdeposits of fibrin that may indicate the potential for a future rupture. However, current methods for evaluating the stage of an atherosclerotic lesion only involve characterizing the level of vessel stenosis, without delineating which lesions are beginning to rupture. Previous work has shown that fibrin-targeted, liquid perfluorocarbon nanoparticles, which carry a high payload of gadolinium, have a high sensitivity and specificity for detecting fibrin with clinical (1)H MRI. In this work, the perfluorocarbon content of the targeted nanoparticles is exploited for the purposes of (19)F imaging and spectroscopy to demonstrate a method for quantifiable molecular imaging of fibrin in vitro at 4.7 T. Additionally, the quantity of bound nanoparticles formulated with different perfluorocarbon species was calculated using spectroscopy. Results indicate that the high degree of nanoparticle binding to fibrin clots and the lack of background (19)F signal allow accurate quantification using spectroscopy at 4.7 T, as corroborated with proton relaxation rate measurements at 1.5 T and trace element (gadolinium) analysis. Finally, the extension of these techniques to a clinically relevant application, the evaluation of the fibrin burden within an ex vivo human carotid endarterectomy sample, demonstrates the potential use of these particles for uniquely identifying unstable atherosclerotic lesions in vivo.
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The water-soluble endohedral gadofullerene derivatives, Gd@C(60)(OH)(x) and Gd@C(60)[C(COOH)(2)](10), have been characterized with regard to their MRI contrast agent properties. Water-proton relaxivities have been measured in aqueous solution at variable temperature (278-335 K), and for the first time for gadofullerenes, relaxivities as a function of magnetic field (5 x 10(-4) to 9.4 T; NMRD profiles) are also reported. Both compounds show relaxivity maxima at high magnetic fields (30-60 MHz) with a maximum relaxivity of 10.4 mM(-1) s(-1) for Gd@C(60)[C(COOH)(2)](10) and 38.5 mM(-1) s(-1) for Gd@C(60)(OH)(x) at 299 K. Variable-temperature, transverse and longitudinal (17)O relaxation rates, and chemical shifts have been measured at three magnetic fields (B = 1.41, 4.7, and 9.4 T), and the results point exclusively to an outer sphere relaxation mechanism. The NMRD profiles have been analyzed in terms of slow rotational motion with a long rotational correlation time calculated to be tau(R)(298) = 2.6 ns. The proton exchange rate obtained for Gd@C(60)[C(COOH)(2)](10) is k(ex)(298) = 1.4 x 10(7) s(-1) which is consistent with the exchange rate previously determined for malonic acid. The proton relaxivities for both gadofullerene derivatives increase strongly with decreasing pH (pH: 3-12). This behavior results from a pH-dependent aggregation of Gd@C(60)(OH)(x) and Gd@C(60)[C(COOH)(2)](10), which has been characterized by dynamic light scattering measurements. The pH dependency of the proton relaxivities makes these gadofullerene derivatives prime candidates for pH-responsive MRI contrast agent applications.
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Quantum dots (QDs), tiny light-emitting particles on the nanometer scale, are emerging as a new class of fluorescent probe for in vivo biomolecular and cellular imaging. In comparison with organic dyes and fluorescent proteins, QDs have unique optical and electronic properties: size-tunable light emission, improved signal brightness, resistance against photobleaching, and simultaneous excitation of multiple fluorescence colors. Recent advances have led to the development of multifunctional nanoparticle probes that are very bright and stable under complex in vivo conditions. A new structural design involves encapsulating luminescent QDs with amphiphilic block copolymers and linking the polymer coating to tumor-targeting ligands and drug delivery functionalities. Polymer-encapsulated QDs are essentially nontoxic to cells and animals, but their long-term in vivo toxicity and degradation need more careful study. Bioconjugated QDs have raised new possibilities for ultrasensitive and multiplexed imaging of molecular targets in living cells, animal models and possibly in humans.
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Neovascularization is a critical component in the progression of malignant melanoma. The objective of this study was to determine whether alpha(nu)beta(3)-targeted paramagnetic nanoparticles can detect and characterize sparse alpha(nu)beta integrin expression on neovasculature induced by nascent melanoma xenografts ( approximately 30 mm(3)) at 1.5T. Athymic nude mice bearing human melanoma tumors were intravenously injected with alpha(v)beta(3)-integrin-targeted paramagnetic nanoparticles, nontargeted paramagnetic nanoparticles, or alpha(v)beta(3)-targeted-nonparamagnetic nanoparticles 2 hr before they were injected with alpha(v)beta(3)-integrin-targeted paramagnetic nanoparticles (i.e., in vivo competitive blockade) and imaged with MRI. Contrast enhancement of neovascularity in animals that received alpha(nu)beta(3)-targeted paramagnetic nanoparticles increased 173% by 120 min. Signal contrast with nontargeted paramagnetic nanoparticles was approximately 50% less than that in the targeted group (P < 0.05). Molecular MRI results were corroborated by histology. In a competitive cell adhesion assay, incubation of alpha(nu)beta(3)-expressing cells with targeted nanoparticles significantly inhibited binding to a vitronectin-coated surface, confirming the bioactivity of the targeted nanoparticles. The present study lowers the limit previously reported for detecting sparse biomarkers with molecular MRI in vivo. This technique may be employed to noninvasively detect very small regions of angiogenesis associated with nascent melanoma tumors, and to phenotype and stage early melanoma in a clinical setting.