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Magnetic-responsive polysaccharide-inorganic composite materials for cancer therapeutics
... For biomedical applications such as cancer theranostics, magnetic NPs should be small enough to be superparamagnetic and stable in a biological medium. Additionally, these NPs should be composed of non-toxic and non-immunogenic materials [6,31]. ...
... This technique is low cost and produces a high yield of magnetic NPs, and by tuning the reaction parameters, adequate control over particle size and distribution can be achieved. The size and shape of the NPs obtained depend on the type of salt used (such as chlorides, sulfates, nitrates, perchlorates), the ferric and ferrous ions ratio, the reaction temperature, the pH, the ionic strength of the media, and the other reaction parameters (e.g., stirring rate, dropping speed of basic solution) [31,32]. ...
... where M stands for Fe, Co, Cu, Zn, Mn, or Ni [6,31]. Gnanaprakash and coworkers [33] studied the effect of digestion time and alkali addition rate on the size and magnetic properties of magnetite NPs produced by chemical co-precipitation. ...
Design, research, and development of new and improved smart multifunctional devices is one of the main topics in the advanced functional materials agenda for the next decade. Smart materials that can be triggered by external stimuli are seen with high potential for innovative treatments and improved drug delivery systems by regulatory agencies like the FDA and EMA. The incorporation of magnetic nanostructures into complex systems produces multifunctional devices that can be spatiotemporally controlled by an external magnetic field. These magneto-responsive devices can be used for a multitude of biomedical applications, from diagnostic to the treatment of tumors, and are actively being developed and tested for cancer theranostics. Herein, we review the development of magneto-responsive devices for cancer theranostics, starting from the most straightforward architecture, single nanoparticles. We give some theoretical concepts about the design and production of such systems while providing a critical review of applications in clinical practice. Naturally, the review evolves to more complex architectures, from one-dimensional to three-dimensional magneto-responsive systems, demonstrating higher complexity and multifunctionality, and consequently, higher interest for clinical practice. The review ends with the main challenges in the design and engineering of magneto-responsive devices for cancer theranostics and future trends in this biomedical field.
... Aside from that, frequencies greater than 8-16 kA.m −1 generate eddy currents that are damaging to normal organs [101,102]. Owing to their super magnetic capabilities, biocompatibility, high specialized region, appropriate nano-sized particulates, and lower toxic effects, Fe2O3 nanomaterials are one of the most promising alternatives for magnetic-responsive devices according to the researchers [31,103,104] (Figure 3). Improved drug loading potential, increased carrier durability, and opportunity for future functionalization might be achieved by coating iron oxide NPs using appropriate polymers [67,[105][106][107][108]. ...
Nanomaterials have demonstrated a wide range of applications and recently, novel biomedical studies are devoted to improving the functionality and effectivity of traditional and unmodified systems, either drug carriers and common scaffolds for tissue engineering or advanced hydrogels for wound healing purposes. In this regard, metal oxide nanoparticles show great potential as versatile tools in biomedical science. In particular, iron oxide nanoparticles with different shape and sizes hold outstanding physiochemical characteristics, such as high specific area and porous structure that make them idoneous nanomaterials to be used in diverse aspects of medicine and biological systems. Moreover, due to the high thermal stability and mechanical strength of Fe2O3, they have been combined with several polymers and employed for various nano-treatments for specific human diseases. This review is focused on summarizing the applications of Fe2O3-based nanocomposites in the biomedical field, including nanocarriers for drug delivery, tissue engineering, and wound healing. Additionally, their structure, magnetic properties, biocompatibility, and toxicity will be discussed.
... In addition, frequencies more than 8-16 kA.m -1 lead to eddy current, which is harmful for healthy tissues [158,159]. Fe 2 O 3 nanoparticles, due to their supermagnetic properties, biocompatibility, high specific area, proper nano-sized particles, and low toxicity, are one of the best candidates for magnetic-responsive systems [160,161]. Coating iron oxide NPs with suitable polymers would improve the drug loading capacity, increase the carrier's stability, and make further functionalization possible [149,[162][163][164][165]. Yan et al. [166] combined Fe 2 O 3 nanoparticles with magnetic fluid hyperthermia (MFH) on human hepatocarcinoma SMMC-7721 cells in vitro and showed dose-dependency of apoptosis and inhibition of proliferation (Fig. 7a). As shown in Fig. (7b), Fe 2 O 3 nanoparticles have magnetic responsiveness, raising the magnetic fluid temperature about 7°C due to their absorption capability. ...
According to the interaction of nanoparticles with biological systems, enthusiasm for nanotechnology in biomedical applications has been developed in the past decades. Fe2O3 nanoparticles, as the most stable iron oxide, have special merits that make them useful widely for detecting diseases, therapy, drug delivery, and monitoring the therapeutic process. This review presents the fabrication methods of Fe2O3-based materials and their photocatalytic and magnetic properties. Then, we highlight the application of Fe2O3-based nanoparticles in diagnosis and imaging, different therapy methods, and finally, stimulus-responsive systems, such as pH-responsive, magnetic-responsive, redox-responsive, and enzyme-responsive, with an emphasis on cancer treatment. In addition, the potential of Fe2O3 to combine diagnosis and therapy within a single particle called theranostic agent will be discussed.
... The therapeutic beneficial properties of MNPs are attractive and also interesting, counting their surface charge, charge density, chemical conformation, shape, inner morphology, size, degradation, and sensitivity to stimuli for the treatment of diseases. 68,136 Chertok et al. effectively transported polyethylenimine (PEI) magnetic nanoparticles to have a saturation of 93 emu g −1 to cancer cells of the brain with low cellular toxicity. 137 A magnetic drug-delivery composite was designed with DOX chemically attached to Fe 3 O 4 nanoparticles. ...
... Alginate has been introduced for use in MRI to aid in cell tracking and to act as a negative control contrast agent [81][82][83]167]. Cellular therapies and labeling are now being implemented with MNPs in conjunction with polysaccharides and proteins to improve medicine [168][169][170][171][172][173][174][175]. ...
The combination of protein and polysaccharides with magnetic materials has been implemented in biomedical applications for decades. Proteins such as silk, collagen, and elastin and polysaccharides such as chitosan, cellulose, and alginate have been heavily used in composite biomaterials. The wide diversity in the structure of the materials including their primary monomer/amino acid sequences allow for tunable properties. Various types of these composites are highly regarded due to their biocompatible, thermal, and mechanical properties while retaining their biological characteristics. This review provides information on protein and polysaccharide materials combined with magnetic elements in the biomedical space showcasing the materials used, fabrication methods, and their subsequent applications in biomedical research.
Rosmarinic acid (RS) is as the nonflavonoid polyphenols in the phenolic acid subgroup was cross‐linked with sodium trimetaphosphate (STMP) to obtain (p[RS‐co‐STMP]) particles with the size distribution of 2.992 ± 659 nm. The zeta potential values of p(RS‐co‐STMP) particles were measured between pH 2–10, and the isoelectric point was determined as pH 2.66. Fe(II) chelating capability test was done for RS and p(RS‐co‐STMP). At 800 μmol/ml concentrations, p(RS‐co‐STMP) particles chelated 95.06 ± 5.18% Fe(II), while RS molecule did not chelate Fe(II), whereas STMP chelated only 41.8 ± 5.9% Fe(II). The effects of RS and p(RS‐co‐STMP) particles on α‐glucosidase enzyme activity were investigated and were found to inhibit the α‐glucosidase enzyme by 55.7% and 89.6%, respectively. Furthermore, p(RS‐co‐STMP) particles were modified with polyethyleneimine as m‐p(RS‐co‐STMP) to improve antimicrobial properties and found effective against both Escherichia coli and Staphylococcus aureus bacteria. The interaction of fibrinogen with RS, p(RS‐co‐STMP) and m‐p(RS‐co‐STMP) were studied via the change in intensity of corresponding fluorescence spectra. It was found that p(RS‐co‐STMP) particles interacted lesser with fibrinogen than RS and changed the fluorescence property of fibrinogen protein slightly. On the other hand, m‐p(RS‐co‐STMP) particles did not change the fluorescence intensity of fibrinogen suggesting no influence on the blood clotting.
The development of smart stimuli-responsive materials for drug delivery offers new opportunities for precise drug release and cancer chemotherapy. A combination of more than one stimuli is highly desirable to further maximize the therapy by taking the advantages of various unique merits. Herein, we employed polyethylene glycol (PEG) functionalized γ-Fe2O3 particles (γ-Fe2O3/PEG) as a novel magnetic drug carrier for doxorubicin (DOX) delivery. The results showed that the γ-Fe2O3/PEG exhibited excellent thermal effects under alternating magnetic field (AMF), high magneto-thermal stability, and large DOX loading capacity. Furthermore, the effects of pH and AMF on the DOX drug release were studied. It was discovered that DOX loaded γ-Fe2O3/PEG carriers were highly responsive to both AMF and pH, resulting in significantly improved cancer cell killing capability over a single stimulus. The magnetic and pH responsive drug delivery system provided a new opportunity to minimize the side effects and maximize the therapeutic efficiency of lung cancer treatment.
Biomineralization is a common process in organisms to produce hard biomaterials by combining inorganic ions with biomacromolecules. Multifunctional nanoplatforms are developed based on the mechanism of biomineralization in many biomedical applications. In the past few years, biomineralization‐based nanoparticle drug delivery systems for the cancer treatment have gained a lot of research attention due to the advantages including simple preparation, good biocompatibility, degradability, easy modification, versatility, and targeting. In this review, the research trends of biomineralization‐based nanoparticle drug delivery systems and their applications in cancer therapy are summarized. This work aims to promote future researches on cancer therapy based on biomineralization. Rational design of nanoparticle drug delivery systems can overcome the bottleneck in the clinical transformation of nanomaterials. At the same time, biomineralization has also provided new research ideas for cancer treatment, i.e., targeted therapy, which has significantly better performance. Biomineralization is a common process in organisms to produce hard biomaterials by combining inorganic ions with biomacromolecules. In the past few years, biomineralization‐based nanoparticle drug delivery systems for cancer treatment have gained a lot of research attention due to the advantages including good biocompatibility, degradability, and targeting. This work aims to promote future researches on cancer therapy based on biomineralization.
Natural biomacromolecules have attracted increased attention as carriers in biomedicine in recent years because of their inherent biochemical and biophysical properties including renewability, nontoxicity, biocompatibility, biodegradability, long blood circulation time and targeting ability. Recent advances in our understanding of the biological functions of natural-origin biomacromolecules and the progress in the study of biological drug carriers indicate that such carriers may have advantages over synthetic material-based carriers in terms of half-life, stability, safety and ease of manufacture. In this review, we give a brief introduction to the biochemical properties of the widely used biomacromolecule-based carriers such as albumin, lipoproteins and polysaccharides. Then examples from the clinic and in recent laboratory development are summarized. Finally the current challenges and future prospects of present biological carriers are discussed. © 2017 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences.
IR780, a near-infrared dye, can also be used as a photosensitizer both for photothermal therapy (PTT) and photodynamic therapy (PDT). In this study, we designed a simple but effective nanoparticle system for carrying IR780 and paclitaxel, thus hoping to combine PTT/PDT and chemotherapy to treat hepatocellular carcinoma (HCC). This nanosystem, named PDF nanoparticles, consisted of phospholipid/Pluronic F68 complex nanocores and pullulan shells. IR780 and paclitaxel were loaded separately into PDF nanoparticles to form PDFI and PDFP nanoparticles, which had regular sphere shapes and relatively small sizes. Upon near-infrared laser irradiation at 808 nm, PDFI nanoparticles showed strong PTT/PDT efficacy both in vitro and in vivo. In MHCC-97H cells, the combined treatment of PDFI nanoparticles/laser irradiation and PDFP nanoparticles exhibited significant synergistic effects on inhibiting cell proliferation and inducing cell apoptosis and cell cycle arrest at G2/M phase. In MHCC-97H tumor-bearing mice, PDFI nanoparticles exhibited excellent HCC-targeting and accumulating capability after intravenous injection. Furthermore, the combined treatment of PDFI nanoparticles/laser irradiation and PDFP nanoparticles also effectively inhibited the tumor growth and the tumor angiogenesis in MHCC-97H tumor-bearing mice. In summary, we put forward a therapeutic strategy for HCC treatment by combining PTT/PDT and chemotherapy.
Magnetic resonance (MR) nano-theranostic hyperthermia uses magnetic nanoparticles to target and accumulate at the lesions and generate heat to kill lesion cells directly through hyperthermia or indirectly through thermal activation and control releasing of drugs. Preclinical and translational applications of MR nano-theranostic hyperthermia are currently limited by a few major theoretical difficulties and experimental challenges in in vivo conditions. For example, conventional models for estimating the heat generated and the optimal magnetic nanoparticle sizes for hyperthermia do not accurately reproduce reported in vivo experimental results. In this work, a revised cluster-based model was proposed to predict the specific loss power (SLP) by explicitly considering magnetic nanoparticle aggregation in in vivo conditions. By comparing with the reported experimental results of magnetite Fe3O4 and cobalt ferrite CoFe2O4 magnetic nanoparticles, it is shown that the revised cluster-based model provides a more accurate prediction of the experimental values than the conventional models that assume magnetic nanoparticles act as single units. It also provides a clear physical picture: the aggregation of magnetic nanoparticles increases the cluster magnetic anisotropy while reducing both the cluster domain magnetization and the average magnetic moment, which, in turn, shift the predicted SLP toward a smaller magnetic nanoparticle diameter with lower peak values. As a result, the heating efficiency and the SLP values are decreased. The improvement in the prediction accuracy in in vivo conditions is particularly pronounced when the magnetic nanoparticle diameter is in the range of ~10–20 nm. This happens to be an important size range for MR cancer nano-theranostics, as it exhibits the highest efficacy against both primary and metastatic tumors in vivo. Our studies show that a relatively 20%–25% smaller magnetic nanoparticle diameter should be chosen to reach the maximal heating efficiency in comparison with the optimal size predicted by previous models.
The increasing number of scientific publications focusing on magnetic materials indicates growing interest in the broader scientific community. Substantial progress was made in the synthesis of magnetic materials of desired size, morphology, chemical composition, and surface chemistry. Physical and chemical stability of magnetic materials is acquired by the coating. Moreover, surface layers of polymers, silica, biomolecules, etc. can be designed to obtain affinity to target molecules. The combination of the ability to respond to the external magnetic field and the rich possibilities of coatings makes magnetic materials universal tool for magnetic separations of small molecules, biomolecules and cells. In the biomedical field, magnetic particles and magnetic composites are utilized as the drug carriers, as contrast agents for magnetic resonance imaging (MRI), and in magnetic hyperthermia. However, the multifunctional magnetic particles enabling the diagnosis and therapy at the same time are emerging. The presented review article summarizes the findings regarding the design and synthesis of magnetic materials focused on biomedical applications. We highlight the utilization of magnetic materials in separation/preconcentration of various molecules and cells, and their use in diagnosis and therapy.
Recently transdermal drug delivery systems (TDDS) based on polymeric nanocomposites have been widely researched by polymer and biomedical scientists for the remedy of various diseases. Thus to develop an efficient patch, we have synthesized guargum-g-polyacrylamide by free radical polymerization using potassium persulphate as an initiator. The transdermal membranes were fabricated via solution casting, by incorporating different wt% of nanosilica and diltiazem hydrochloride to the synthesized copolymer. The resulting copolymer and the nanocomposite membranes were characterized using solid state 13C nuclear magnetic resonance, Fourier transform infrared spectra, thermo-gravimetric analysis, electron microscopy and viscometry. Hydro-swelling study and surface contact angle measurement showed that the membrane containing 1 wt% nanosilica was most hydrophobic. In-vitro drug release pattern of all the transdermal membranes showed that the nanocomposite containing 1 wt% nanosilica provide the best result with 8.58 and 24.76% drug release after 5 and 20 h, respectively. Furthermore, the nanocomposite formulation exhibited good cyto-compatibility and non-irritant behaviour which are primary requirement for an efficient transdermal drug delivery system.
Magnetic nanoparticles, such as superparamagnetic iron oxide nanoparticles (SPIONs) emerged as therapeutic and diagnostic agents due to their biocompatibility, bioselectivity, prolonged circulation, and chemical stability. The aim of this study was to develop novel polymeric-metallic hybrid nanoparticles coated with glycol chitosan (poly-(1,4-β-D-glucopyranosamine); GC) and loaded with progesterone. The crystalline nanoparticles were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), thermo-gravimetric analysis (TGA), and vibrating sample magnetometer (VSM). Spherical-like superparamagnetic GC coated nanoparticles in the size range of 10–20 nm were prepared. Progesterone release mechanism from GC hybrid magnetic nanoparticles was investigated with the aid of mathematical models. Progesterone release kinetics was shown to differ significantly with pH changes where GC-coated superparamagnetic nanoparticles (Fe3O4-GC) exhibited swelling at pH 6.5 and shrinkage at pH 7.4. Moreover, metabolic activity assay of C3H10T1/2 cell line cultured with SPION-GC indicated biocompatibility of the magnetic nanoparticles. Taken together, polymeric-metallic hybrid nanoparticles have shown to be a promising nanocarrier system for controlled drug delivery applications.
pH-responsive magnetic micelles are beneficial for time-controlled and site-specific drug delivery without triggering potential biological side effects. In this study, gelatin-g-poly(NIPAAm-co-DMAAm-co-UA)-g-dextran/Fe3O4 (GPDF) pH-responsive magnetic micelles were synthesized to carry a hydrophilic insulin-promoting factor, nicotinamide. The chemical structures were analyzed via Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. Superconducting quantum interference device (SQUID) analysis confirmed the superparamagnetic property of the GPDF micelle. The accumulative nicotinamide release under pathological pH conditions (pH 6.6) was found to be three-fold higher than that under normal pH conditions (pH 7.2). The results suggest that GPDF is beneficial for a pH-selective and magnetic target-controlled release drug delivery system.
Clusters of magnetic nanoparticles have received considerable interest in various research fields. Their capacity to generate heat under an alternating magnetic field has recently opened the way to applications such as cancer therapy by hyperthermia. This work is an attempt to investigate the collective effects of interacting dipoles embedded in magnetic nano-particles (MNP) to predict their thermal dissipation with a liquid. We first present a general approach, based on the tracking of the microscopic dipole fluctuations, to access to the dissipation spectra of any spatial distribution of MNPs. Without any other assumption that the linear response regime, it is shown that increasing the particle concentration (dipolar interactions) dramatically diminishes and blueshifts the dissipation processes. This effect originates in a predominance of the coupling energy over the Brownian torques, which create a long-range ordering that saturates the response of the system to an external field. Consequently, the particle density is of fundamental importance to the control of the absorption of electromagnetic energy and its subsequent dissipation in the form of heat.
Chitosan (CS) iron oxide magnetic nanoparticles (MNPs) were coated with phytic acid (PTA) to form phytic acid-chitosan-iron oxide nanocomposite (PTA-CS-MNP). The obtained nanocomposite and nanocarrier were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, vibrating sample magnetometry, transmission electron microscopy, and thermogravimetric and differential thermogravimetric analyses. Fourier transform infrared spectra and thermal analysis of MNPs and PTA-CS-MNP nanocomposite confirmed the binding of CS on the surface of MNPs and the loading of PTA in the PTA-CS-MNP nanocomposite. The coating process enhanced the thermal stability of the anticancer nanocomposite obtained. X-ray diffraction results showed that the MNPs and PTA-CS-MNP nanocomposite are pure magnetite. Drug loading was estimated using ultraviolet-visible spectroscopy and showing a 12.9% in the designed nanocomposite. Magnetization curves demonstrated that the synthesized MNPs and nanocomposite were superparamagnetic with saturation magnetizations of 53.25 emu/g and 42.15 emu/g, respectively. The release study showed that around 86% and 93% of PTA from PTA-CS-MNP nanocomposite could be released within 127 and 56 hours by a phosphate buffer solution at pH 7.4 and 4.8, respectively, in a sustained manner and governed by pseudo-second order kinetic model. The cytotoxicity of the compounds on HT-29 colon cancer cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The HT-29 cell line was more sensitive against PTA-CS-MNP nanocomposite than PTA alone. No cytotoxic effect was observed on normal cells (3T3 fibroblast cells). This result indicates that PTA-CS-MNP nanocomposite can inhibit the proliferation of colon cancer cells without causing any harm to normal cell.
The aim of the present work was to develop green carriers for methotrexate using κ-carrageenan/chitosan complexes. Magnetic Fe3O4 nanoparticles were first synthesized in the presence of κ-carrageenan through in situ method. Then, the obtained magnetic κ-carrageenan was crosslinked using the polycation chitosan biopolymer. The physical and structural properties of hydrogels were investigated by FTIR, XRD, SEM, TEM, TGA, and VSM techniques. The pH-dependent swelling behavior of hydrogels was examined in various buffer solutions. All of the prepared hydrogels showed a high swelling capacity in basic solutions. The introduction of magnetite nanoparticles into κ-carrageenan/chitosan complexes had a significant effect on the swelling capacity of magnetic hydrogels, as the water absorbency of hydrogels decreased with increasing magnetite content. Methotrexate as an anticancer and model drug was loaded on hydrogels and the release profiles were investigated at pH = 7.4 and 5.3. The methotrexate encapsulation efficiency was increased by increasing magnetite and chitosan contents. The results demonstrated that the release of methotrexate from magnetic hydrogels is pH-dependent with a high release content at pH = 7.4. The release profiles were analyzed by Peppas’s empirical model and the release of drug from hydrogels followed Fickian type of diffusion mechanism at both pHs.
Magnetic hyperthermia with the treating temperature range of 41–46 °C is an alternative therapy for cancer treatment. In this article, lanthanum strontium manganates (La1−xSrxMnO3, 0.25 ≤ × ≤ 0.35) magnetic nanoparticles coated by hyaluronic acid (HA) which possesses the ability of targeting tumor cells were prepared by a simple hydrothermal method combined with a high-energy ball milling technique. The crystal structure, morphology, magnetic properties of the HA-coated magnetic nanoparticles (MNPs), and their heating ability under alternating magnetic field were investigated. It was found the HA-coated La0.7Sr0.3MnO3, with particle diameter of ~100 nm, Curie temperature of 45 °C at a concentration 6 mg/ml, gave the optimal induction heating results. The heating temperature saturates at 45.7 °C, and the ESAR is 5.7 × 10⁻³ W/g · kHz · (kA/m²) which is much higher than other reported results.
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Recent advancements in imaging diagnostics have focused on the use of nanostructures that entrap Magnetic Resonance Imaging (MRI) Contrast Agents (CAs), without the need to chemically modify the clinically approved compounds. Nevertheless, the exploitation of microfluidic platforms for their controlled and continuous production is still missing. Here, a microfluidic platform is used to synthesize crosslinked Hyaluronic Acid NanoParticles (cHANPs) in which a clinically relevant MRI-CAs, gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA), is entrapped. This microfluidic process facilitates a high degree of control over particle synthesis, enabling the production of monodisperse particles as small as 35 nm. Furthermore, the interference of Gd-DTPA during polymer precipitation is overcome by finely tuning process parameters and leveraging the use of hydrophilic-lipophilic balance (HLB) of surfactants and pH conditions. For both production strategies proposed to design Gd-loaded cHANPs, a boosting of the relaxation rate T1 is observed since a T1 of 1562 is achieved with a 10 μM of Gd-loaded cHANPs while a similar value is reached with 100 μM of the relevant clinical Gd-DTPA in solution. The advanced microfluidic platform to synthesize intravascularly-injectable and completely biocompatible hydrogel nanoparticles entrapping clinically approved CAs enables the implementation of straightforward and scalable strategies in diagnostics and therapy applications.
Dual-function hydrogels, possessing both stimuli-responsive and self-healing properties, have recently attracted attention of both chemists and materials scientists. Here we report a new paradigm using natural polymer (guar gum, GG) and sodium borohydride (NaBH4), for the preparation of silver nanoparticles (AgNPs)-containing smart hydrogels in a simple, fast and economical way. NaBH4 performs as a reducing agent for AgNPs synthesis using silver nitrate (AgNO3) as the precursor. Meanwhile, sodium metaborate (NaBO2) (from NaBH4) behaves as a cross-linking agent between GG molecular chains. The AgNPs/GG hydrogels with excellent viscoelastic properties can be obtained within 3 min at room temperature without the addition of other cross-linkers. The resultant AgNPs/GG hydrogels are flowable and injectable, and they possess excellent pH/thermal responsive properties. Additionally, they exhibit rapid self-healing capacity. This work introduces a facile and scale-up way to prepare a class of hydrogels that can have great potential to biomedical and other industrial applications.
In this work anti-cancer drug curcumin-loaded superparamagnetic iron oxide (Fe3O4) nanoparticles was modified by chitosan (CS). The magnetic iron oxide nanoparticles were synthesized by using reverse micro-emulsion (water-in-oil) method. The magnetic nanoparticles without loaded drug and drug-loaded magnetic nanoparticles were characterized by XRD, FTIR, TG-DTA, SEM, TEM, and VSM techniques. These nanoparticles have almost spherical shape and their diameter varies from 8 nm to 17 nm. Measurement of VSM at room temperature showed that iron oxide nanoparticles have superparamagnetic properties. In vitro drug loading and release behavior of curcumin drug-loaded CS-Fe3O4 nanoparticles were studied by using UV-spectrophotometer. In addition, the cytotoxicity of the modified nanoparticles has shown anticancer activity against A549 cell with IC50 value of 73.03 μg/ml. Therefore, the modified magnetic nanoparticles can be used as drug delivery carriers on target in the treatment of cancer cells.
To search for nano-drug preparations with high efficiency in tumor treatment, we evaluated the drug-loading capacity and cell-uptake toxicity of three kinds of nanoparticles (NPs). Pullulan was grafted with ethylenediamine and hydrophobic groups to form hydrophobic cholesterol-modified amino-pullulan (CHAP) conjugates. Fourier transform infrared spectroscopy and nuclear magnetic resonance were used to identify the CHAP structure and calculate the degree of substitution of the cholesterol group. We compared three types of NPs with close cholesterol hydrophobic properties: CHAP, cholesterol-modified pullulan (CHP), and cholesterol-modified carboxylethylpullulan (CHCP), with the degree of substitution of cholesterol of 2.92%, 3.11%, and 3.46%, respectively. As compared with the two other NPs, CHAP NPs were larger, 263.9 nm, and had a positive surface charge of 7.22 mV by dynamic light-scattering measurement. CHAP NPs showed low drug-loading capacity, 12.3%, and encapsulation efficiency of 70.8%, which depended on NP hydrophobicity and was affected by surface charge. The drug release amounts of all NPs increased in the acid media, with CHAP NPs showing drug-release sensitivity with acid change. Cytotoxicity of HeLa cells was highest with mitoxantrone-loaded CHAP NPs on MTT assay. CHAP NPs may have potential as a high-efficiency drug carrier for tumor treatment.
Hematite (α-Fe 2 O 3) nanoparticles with three different polysaccharide templates namely CF, SAF and PF are successfully synthesized via simple thermal decomposition method. The structural morphology and magnetic behavior of hematite nanoparticles have been investigated by X-ray diffractometer (XRD), Fourier transform infrared spectroscopy (FT-IR),high resolution scanning electron microscopy (HRSEM), high resolution transmission electron microscopy (HRTEM) and vibrating sample magnetometer (VSM). XRD measurements confirmed the formation of pure phase α-Fe 2 O 3 nanoparticles and the presence of α-phase of Fe 2 O 3 was confirmed by FTIR spectroscopy. The particle size was calculated by HRTEM measurements and it turns out to be 98nm, 77nm and 84nm for CF, SAF and PF respectively. Magnetic measurements display hysteretic behavior at the room temperature with saturation magnetization M S = 0.532emu/g, 0.427emu/g, 0.457emu/g and coercivity H C = 1718Oe, 860Oe, 1211Oe for CF, SAF and PF respectively. The antibacterial test showed inhibition against S.aureus and E. coli with significant antagonistic activity.
ZnS:Mn–Fe3O4 bifunctional nanoparticles were synthesized by inverse microemulsion method for biomedicine applications. The bifunctional nanoparticles were combined from prepared ZnS:Mn and Fe3O4 nanoparticles in a SiO2 cover matrix. Results show that bifunctional nanoparticles, apart from exhibiting magnetism, have photoluminescence properties, which support the applications targeting biomedicine fluorescent diagnostics as well as magnetic cell sorting or drug delivery.
Mechanical stimulus is one of the universally accessible physical ways of triggering the drug release from their carriers. Hollow microcapsules made of polyelectrolyte multilayers by conventional methods are not elastic enough to respond to a large and repetitive mechanical deformation. Here, hybrid hollow capsules comprising alternating layers of inorganic colloidal particles and biopolymers were prepared by the layer-by-layer approach followed by freezing-assisted crosslinking of polymer layers. The size of the capsule was controllable by the size of sacrificial cores. These hybrid capsules were mechanically more stable and recover faster than polyelectrolyte capsules, and could be recovered elastically even after large and repetitive deformation up to 98% relative to their original dimensions. Drugs in a wide range of molecular weight up to 70 kDa Mw could be loaded into the hollow hybrid microcapsules and the release of loaded contents from these hybrid capsules could be controlled through the deformation by applying a weak force such as a finger pressing on them. Mechanical stimuli-responsive delivery of model drugs was demonstrated on a monolayer of these hybrid capsules.
Multidrug resistance (MDR) and targeted therapies present major challenges in tumor chemotherapy. Nanoparticles (NPs) hold promise for use in cancer theranostics due to their advantages in terms of tumor-targeted cytotoxicity and imaging. In this study, we developed N-((2-hydroxy-3-trimethylammonium) propyl) chitosan chloride (HTCC)/alginate-encapsulated Fe3O4 magnetic NPs (HTCC-MNPs) and applied them to MDR gastric cancer both in vivo and in vitro. HTCC-MNPs were fabricated from sodium alginate (ALG), Fe3O4 and HTCC using an ionic gelation method. The sizes and physical characteristics of the NPs were determined using dynamic light scattering, transmission electron microscopy (TEM) and zeta potential analysis. The HTCC-MNPs exhibited excellent water solubility and biocompatibility as well as significantly reduced cell viability in the drug-resistant cancer cell line SGC7901/ADR, but not in normal gastric cells (P < 0.05). An analysis of LC3 expression demonstrated the involvement of autophagy in HTCC-MNP cytotoxicity. Additionally, apoptosis was verified using a DNA content assay. HTCC-MNPs led to mitochondrial membrane potential loss, decreased ATP production and excessive reactive oxygen species (ROS) generation compared to a control group (P < 0.05). Magnetic resonance imaging showed enrichment of HTCC-MNPs in tumor-bearing mice. In vivo bioluminescence imaging and tumor volume measurements revealed that HTCC-MNPs markedly inhibited in vivo tumor growth (P < 0.05). In conclusion, HTCC-MNPs significantly inhibited MDR gastric tumor growth and reduced tumor volume via the induction of cellular autophagy and apoptosis, which was attributed to mitochondrial dysfunction and excessive ROS accumulation.
Drug delivery system with controlled release technology has emerged as a powerful tool for the treatment of various diseases. The therapeutic index of the active agent can be enhanced by increasing its stability, solubility and bioavailability, along with specific site delivery. Polymers have been playing an integral role as carrier in formulating an efficient drug delivery system by their stability, drug loading capacity and tunable properties. 'Chitosan' the natural cationic polymer derived from chitin has received growing attention mainly due to their biodegradable, biocompatible, non-toxic, mucoadhesive and ability to target specific delivery properties. Chitosan has itself many medicinal properties like antimicrobial, antioxidant, low immunogenicity etc. which enhance its potential in different biomedical applications. The various techniques for preparation of chitosan micro/nano particles are discussed in this review. Various types of chitosan based drug delivery systems are surveyed to elucidate its role in different biomedical applications.
Due to their unique structures and properties, three-dimensional hydrogels and nanostructured particles have been widely studied and shown a very high potential for medical, therapeutic and diagnostic applications. However, hydrogels and nanoparticulate systems have respective disadvantages that limit their widespread applications. Recently, the incorporation of nanostructured fillers into hydrogels has been developed as an innovative means for the creation of novel materials with diverse functionality in order to meet new challenges. In this review, the fundamentals of hydrogels and nanoparticles (NPs) were briefly discussed, and then we comprehensively summarized recent advances in the design, synthesis, functionalization and application of nanocomposite hydrogels with enhanced mechanical, biological and physicochemical properties. Moreover, the current challenges and future opportunities for the use of these promising materials in the biomedical sector, especially the nanocomposite hydrogels produced from hydrogels and polymeric NPs, are discussed.
This review focuses on the most recent developments in the field of nanocomposite hydrogels intended for biomedical applications. Nanocomposite hydrogels are hydrated polymeric networks with a physically or covalently crosslinked three-dimensional (3D) structure swollen with water, in the presence of nanoparticles or nanostructures. A wide array of nanomaterials (polymeric, carbon-based, metallic, ceramic) can be incorporated within the hydrogel network to obtain reinforced nanocomposite hydrogels. Nanocomposites represent a new class of materials with properties absent in the individual components. In particular, the incorporation of nanomaterials within a polymeric hydrogel network is an attractive approach to tailor the mechanical properties of the hydrogels and/or to provide the nanocomposite with responsiveness to external stimuli.
Polymer nanocomposites are increasingly important in food packaging sectors. Biopolymer pullulan is promising in manufacturing packaging films or coatings due to its excellent optical clarity, mechanical strength, and high water-solubility as compared to other biopolymers. This work aims to enhance its oxygen barrier properties and overcome its intrinsic brittleness by utilizing two-dimensional planar graphene oxide (GO) nanoplatelets. It has been found that the addition of only 0.2 wt% of GO enhanced the tensile strength, Young's modulus, and elongation at break of pullulan films by about 40, 44 and 52%, respectively. The light transmittance at 550 nm of the pullulan/GO films was 92.3% and haze values were within 3.0% threshold, which meets the general requirement for food packaging materials. In particular, the oxygen permeability coefficient of pullulan was reduced from 6337 to 2614 mL μm m −2 (24 h −1) atm −1 with as low as 0.05 wt% of GO loading and further to 1357 mL μm m −2 (24 h −1) atm −1 when GO concentration reached 0.3 wt%. The simultaneous improvement of the mechanical and oxygen barrier properties of pullulan was ascribed to the homogeneous distribution and prevalent unidirectional alignment of GO nanosheets, as determined from the characterization and theoretical modelling results. The exceptional oxygen barrier properties of pullulan/GO nanocomposites with enhanced mechanical flexibility and good optical clarity will add new values to high performance food packaging materials. S Online supplementary data available from stacks.iop.org/NANO/26/275703/mmedia
Today, nanotechnology plays a vital role in biomedical applications, especially for the diagnosis and treatment of various diseases. Among the many different types of fabricated nanoparticles, magnetic metal oxide nanoparticles stand out as unique and useful tools for biomedical applications, because of their imaging characteristics and therapeutic properties such as drug and gene carriers. Polymer-coated magnetic particles are currently of particular interest to investigators in the fields of nanobiomedicine and fundamental biomaterials. Theranostic magnetic nanoparticles that are encapsulated or coated with polymers not only exhibit imaging properties in response to stimuli, but also can efficiently deliver various drugs and therapeutic genes. Even though a large number of polymer-coated magnetic nanoparticles have been fabricated over the last decade, most of these have only been used for imaging purposes. The focus of this review is on polysaccharide-coated magnetic nanoparticles used for imaging and gene delivery.
Hyperthermia is one of the promising treatments for cancer therapy. However, the development of a magnetic fluid agent that can selectively target a tumor and efficiently elevate temperature while exhibiting excellent biocompatibility still remains challenging. Here a new core-shell nanostructure consisting of inorganic iron oxide (Fe3O4) nanoparticles as the core, organic alginate as the shell, and cell-targeting ligands (ie, D-galactosamine) decorated on the outer surface (denoted as Fe3O4@Alg-GA nanoparticles) was prepared using a combination of a pre-gel method and coprecipitation in aqueous solution. After treatment with an AC magnetic field, the results indicate that Fe3O4@Alg-GA nanoparticles had excellent hyperthermic efficacy in a human hepatocellular carcinoma cell line (HepG2) owing to enhanced cellular uptake, and show great potential as therapeutic agents for future in vivo drug delivery systems.
In this work, La0.7Sr0.3−xBaxMnO3 (0 ≤ x ≤ 0.15) magnetic nanoparticles were synthesized using a simple sol–gel method in the presence of polyvinyl alcohol as a chelating agent. Then the nanoparticles are coated by hyaluronic acid as the surfactant via high-energy ball milling for their possible application in biocompatible magnetic fluid hyperthermia. The samples were characterized by X-ray diffraction, vibrating sample magnetometry, scanning electron microscopy, high-resolution transmission electron microscopy, Fourier-transform infrared spectroscopy and high-frequency induction heating studies. It was found that the hyaluronic acid-coated La0.7Sr0.25Ba0.05MnO3 nanoparticles, with a particle diameter of ∼100 nm and a Curie temperature of 67 °C at a concentration of 5 mg mL⁻¹, gave the optimal induction heating results. The saturation heating temperature, the specific absorption rate, and the effective specific absorption rate are 44.1 °C, 60.1 W g⁻¹ and 0.14 W g⁻¹ kHz (kA m⁻²), respectively. The hyaluronic acid-coated La0.7Sr0.25Ba0.05MnO3 nanoparticles with a suitable saturation heating temperature and a high specific absorption rate can be used as an effective heating source for the hyperthermia treatment of cancer. Their targeting ability towards cancer cells and good biocompatibility were also proved by cell experiments.
In this study, 3D biopolymeric materials based on the blends of collagen (Coll), chitosan (CTS), and hyaluronic acid (HA) were prepared by lyophilization technique. Magnetic particles synthesized by precipitation of iron (II) sulfate heptahydrate and iron (III) chloride hexahydrate in an aqueous solution of chitosan were added to a biopolymer mixture. Dialdehyde starch (DAS) was used as a cross-linking agent for the materials. The structure of the obtained materials was studied using infrared spectroscopy and scanning electron microscope imaging. The properties of the 3D materials such as density, porosity, swelling ability and mechanical properties were studied. It was found that 3D composites made from collagen, chitosan, and hyaluronic acid with magnetic particles are hydrophilic with a high swelling ability (up to 2,646%). Cross-linking of such biopolymeric materials with DAS alters the swelling degree and porosity of materials. The cross-linking process has no significant effect on the density of the materials. The addition of magnetic particles to Coll/CTS/HA materials decreases its swelling ability (1,795% for material containing 30% of magnetic particles) and increases the density of the studied materials. 3D materials based on Coll/CTS/HA with magnetic particles are rigid and inflexible. With the increasing content of magnetic particles in the polymer blend, the Young's modulus decreases. 3D material with magnetite particles can be used in biomedical applications, such as tissue repair and drug delivery.
TiO2/Fe3O4, TiO2/Fe3O4/chitosan and Methylpyrazolone functionalized TiO2/Fe3O4/chitosan (MPyTMChi) were successfully prepared. The chemical structure of the prepared materials was confirmed by FT-IR spectra, XRD, SEM and TEM. BET surface area increased from 2.4 to 3.1m(2)/g, Eg decreased from 2.58 to 2.25eV and more quenching of PL emission spectra was observed upon functionalization of TMChi by MPy. Moreover, high Ti and oxygen percentages were detected by EDX. Magnetization value (Ms) reached 21 emu.g(-1) for MPyTMChi. MPyTMChi showed enhanced photocatalytic degradation rate of methylene blue (MB) dye under visibe light irradiation (99.8% after 40min) as compared with that for TiO2/Fe3O4 (96.7% after 100min) and TMChi (98.9% after 60min), respectively. It was regarded that the photocatalytic degradation of MB dye on MPyTMChi follows apparent pseudo-first-order according to the Langmuir-Hinshelwood (L-H) model and kapp value was 0.089min(-1). Active species trapping experiment revealed that h(+) and O2(-) played the main role in the photodegradation of MB dye while OH quenching did not greatly affect photodegradation rate. Additionally, MPyTMChi can be efficiently reused for six repetitive cycles. MPyTMChi showed higher antimicrobial activity against gram-positive, gram- negative bacterial and fungal strains while large inhibiton zone was observed for gram-positive bacteria.
Multifunctional capsules have great applications in biomedical fields. In this study, novel polysaccharide-based nanocapsules were prepared via a layer-by-layer technique using silica as the templates. The shell was constructed based on the electrostatic interactions between pectin and chitosan. The pectin-chitosan nanocapsules ((Pec/Cs)3Pec) could keep good colloidal stability within 96 h in PBS solution and 48 h in BSA solution. Meanwhile, the nanocapsules exhibited a high drug loading and pH-sensitive release property for doxorubicin hydrochloride. Moreover, (Pec/Cs)3Pec nanocapsules had no cytotoxicity to both human hepatocellular carcinoma cells (HepG2 cells) and mouse fibroblast cells (L929 cells). More importantly, (Pec/Cs)3Pec nanocapsules could be more easily uptaken by HepG2 cells when compared with L929 cells. In vitro anticancer activity tests indicated the carriers could effectively kill HepG2 cells. Overall, (Pec/Cs)3Pec nanocapsules have great potential as a novel anticancer drug carrier as a result of their pH-sensitivity, good colloidal stability and anticancer activity.
Facile and “green” techniques for hydrogel fabrication are in high demand to satisfy a wide range of practical applications. To the best of our knowledge, this report presents the first description of an efficient, one-flask method for preparing a guar gum (GG)-based self-assembling hydrogel, which takes advantage of the formation of cyclic acetals between the vicinal hydroxyl groups and carbonyl groups, as introduced via the regioselective oxidation of GG using sodium periodate (NaIO4). The final product was achieved without the addition of any crosslinking agents. The self-assembling hydrogel was rapidly formed under ambient conditions, and demonstrated remarkable self-healing performance, as well as thermally responsive properties associated with sol-gel transitions. Furthermore, the GG hydrogel had the ability to remove copper ions (Cu²⁺) from the surrounding aqueous solution. This removal can be accounted for due to the large number of active sites (i.e., hydroxyl groups) within its porous three-dimensional structure. The adsorption equilibrium was achieved after 5 h, and the amount of adsorbed Cu²⁺ was 944 mg/g GG when an initial concentration of 25 mg/mL CuSO4 in solution was used. The adsorption isotherm data correlated well with the Freundlich model (R² > 0.99), suggesting that the Cu²⁺ was removed through multilayered and complex adsorption mechanisms.
Multifunctional theranostics have offered some interesting new opportunities for cancer therapy and diagnosis in the last decade. Herein, magnetic mesoporous silica nanoparticles (M-MSNs) were designed and synthesized, then the photosensitizer chlorin e6 (Ce6) and antitumor drug doxorubicin (Dox) were adsorbed onto the M-MSNs. Biocompatible alginate/chitosan polyelectrolyte multilayers (PEM) were assembled on the M-MSNs to achieve a pH-responsive drug delivery system and adsorb P-gp shRNA for reversing the multidrug resistance. The obtained M-MSN(Dox/Ce6)/PEM/P-gp shRNA nanocomposites were characterized using TEM, SEM, X-ray diffraction, BET, FTIR and electrophoresis. The nanocomposites with average diameter of 280 nm exhibited a pH-responsive drug release profile, and more singlet oxygen generation in cancer cells after laser illumination. CCK-8 assay and calcein-AM/PI co-staining showed that the multifunctional nanocomplexes significantly increased cell apoptosis in vitro. With tumor-bearing Balb/c mice employed as the animal model, combined photodynamic therapy and chemotherapy was carried out, also achieving synergistic anti-tumor effects in vivo. The cores of bifunctional Fe3O4–Au nanoparticles in the multifunctional nanocomposites enabled dual-modal MR and CT imaging, which illustrated strong tumor uptake of these nanocomposites after intravenous injection into tumor-bearing mice. This work highlights the great potential of magnetic mesoporous silica nanocomposites as a multifunctional delivery platform, which is promising for imaging-guided cancer combination therapy with high efficacy.
Developing a drug carrier system which could perform targeted and controlled release over a period of time is utmost concern in the pharmaceutical industry. This is more relevant when designing drug carriers for poorly water soluble drug molecules such as curcumin and 6-gingerol. Development of a drug carrier system which could overcome these limitations and perform controlled and targeted drug delivery is beneficial. This study describes a promising approach for the design of novel pH sensitive sodium alginate, hydroxyapatite bilayer coated iron oxide nanoparticle composite (IONP/HAp-NaAlg) via the co-precipitation approach. This system consists of a magnetic core for targeting and a NaAlg/ HAp coating on the surface to accommodate the drug molecules. The nanocomposite was characterized using FT-IR spectroscopy, X-ray diffraction, scanning electron microscopy, transmission electron microscopy and thermogravimetric analysis. The loading efficiency and loading capacity of curcumin and 6-gingerol were examined. The in-vitro drug releasing behavior of curcumin and 6-gingerol was studied at pH 7.4 and pH 5.3 over a period of seven days at 37 °C. The mechanism of drug release from the nanocomposite of each situation was studied using kinetic models and the results implied that, the release is typically via diffusion and a higher release was observed at pH 5.3. This bilayer coated system can be recognized as a potential drug delivery system for the purpose of curcumin and 6-gingerol release in targeted and controlled manner to treat diseases such as cancer.
The aim of this work is to prepare and evaluate a novel lipid-polymer hybrid liposomal nanoplatform (hyaluronic acid-magnetic nanoparticle-liposomes, HA-MNP-LPs) as a vehicle for targeted delivery and triggered release of an anticancer drug (docetaxel, DTX) in human breast cancer cells. We first synthesize an amphiphilic hyaluronic acid hexadecylamine polymer (HA-C16) to enhance the targeting ability of the hybrid liposome. Next, HA-MNP-LPs are constructed to achieve an average size of 189.93 ± 2.74 nm in diameter. In addition, citric acid-coated magnetic nanoparticles (MNPs) are prepared and embedded in the aqueous cores while DTX is encapsulated in the hydrophobic bilayers of the liposomes. Experiments with coumarin 6 loaded hybrid liposomes (C6/HA-MNP-LPs) show that the hybrid liposomes have superior cellular uptake in comparison with the conventional non-targeting liposomes (C6/MNP-LPs), and the result is further confirmed by Prussian blue staining. Under near-infrared laser irradiation (NIR, 808 nm), the HA-MNP-LPs aqueous solution can reach 46.7 °C in 10 min, and the hybrid liposomes released over 20% more drug than non-irradiated liposomes. Using a combination of photothermal irradiation and chemotherapy, the DTX-loaded hybrid liposomes (DTX/HA-MNP-LPs) significantly enhance therapeutic efficacy, with the IC50 value of 0.69 ± 0.10 μg/mL, which is much lower than the values for radiation monotherapy or DTX monotherapy. Consequently, the prepared hybrid nanoplatform may offer a promising drug delivery vehicle with selective targeting and enhanced drug release in treating CD44-overexpressing cancers.
A novel, magnetic nanocarrier was successfully synthesized through a facile and economical producer in which Fe3O4 magnetic nanoparticles were coated by starch-g-poly (methyl methacrylate-co-PEG-acrylamide). The surface of nanocarrier was then modified by hydrazine to preparation of a pH-responsive carrier. The resulted nanocarrier was applied for delivery of doxorubicin (DOX) as an effective anti-cancer drug. DOX was reacted with hydrazine linkage on the surface of nanocarrier to form hydrazone bond. Due to the presence of numerous hydrazine groups on the surface of magnetic nanocarrier large amounts of DOX was loaded onto the carrier (327 mg g−1).
Targeted delivery of anti-cancer drugs increase the efficacy, while decreasing adverse effects. Among various delivery systems, chitosan coated iron oxide nanoparticles (CsMNPs) gained attention with their biocompatibility, biodegradability, low toxicity and targetability under magnetic field. This study aimed to increase the cellular uptake and efficacy of Gemcitabine. CsMNPs were synthesized by in situ co-precipitation and Gemcitabine was loaded onto the nanoparticles. Nanoparticle characterization was performed by TEM, FTIR, XPS, and zeta potential. Gemcitabine release and stability was analyzed. The cellular uptake was shown. Cytotoxicity of free-Gemcitabine and Gem-CsMNPs were examined on SKBR and MCF-7 breast cancer cells by XTT assay. Gemcitabine loading was optimized as 30µM by spectrophotometric analyses. Drug release was highest (65%) at pH4.2, while it was 8% at pH7.2. This is a desired release characteric since pH of tumor-tissue and endosomes are acidic, while the blood-stream and healthy-tissues are neutral. Peaks reflecting the presence of Gemcitabine were observed in FTIR and XPS. At neutral pH, zeta potential increased after Gemcitabine loading. TEM images displayed, Gem-CsMNPs were 4nm with uniform size-distribution and have spherical shape. The cellular uptake and targetability of CsMNPs was studied on MCF-7 breast cancer cell lines. IC50 value of Gem-CsMNPs was 1.4 fold and 2.6 fold lower than free-Gem on SKBR-3 and MCF-7 cell lines respectively, indicating the increased efficacy of Gemcitabine when loaded onto nanoparticles. Targetability by magnetic field, stability, size distribution, cellular uptake and toxicity characteristics of CsMNPs in this study provides a useful targeted delivery system for Gemcitabine in cancer therapy.
Carboxymethyl guar gum (CMGG) synthesized from commercially available polysaccharide was formulated into nanoparticles via ionic gelation using trisodium trimetaphosphate (STMP) as cross-linking agent. Characterisation using a range of analytical techniques (FTIR, NMR, GPC, TGA and DLS) confirmed the CMGG structure and revealed the effect of the CMGG and STMP concentration on the main characteristics of the obtained nanoformulations. The average nanoparticle diameter was found to be around 208 nm, as determined by dynamic light scattering (DLS) and confirmed by scanning electron microscopy (SEM) and nanoparticle tracking analysis (NTA). Experiments using simulated gastric and intestinal fluids evidenced significant pH-dependent drug release behaviour of the nanoformulations loaded with Rhodamine B (RhB) as a model drug (loading capacity in excess of 83%), as monitored by UV–Vis. While dose-dependent cytotoxicity was observed, the nanoformulations appeared completely non-toxic at concentrations below 0.3 mg/mL. Results obtained so far suggest that carboxymethylated guar gum nanoparticles formulated with STMP warrant further investigations as polysaccharide based biocompatible drug nanocarriers.
This paper reports the synthesis of magnetic and pH-sensitive beads derived from kappa-carrageenan and carboxymethyl chitosan for drug delivery. The magnetic Fe3O4 nanoparticles were synthesized inside a mixture of biopolymers by in situ method. The structural properties of hydrogel beads were characterized by TEM, SEM, XRD, and VSM techniques. The swelling ratio of beads indicated pH-dependent properties with maximum water absorbing at pH 7.4. Introducing magnetic nanoparticles caused a decrease in swelling capacity from 16.4 to 10 g/g. Drug loading and release efficiency were investigated using diclofenac sodium as a model system. The in vitro drug release studies exhibited significant behaviors on the subject of physiological simulated pHs and external alternative magnetic fields. The maximum cumulative release was around 82% at pH 7.4. The presence of magnetite nanoparticles certainly influenced the drug release patterns. The response of beads to external stimulus makes them as good candidates for novel drug delivery systems.
Core–shell nanoparticles, magnetic core and gold shell, were synthesized by reduction of gold chloride on the surface of magnetic nanoparticles; using tyrosine as a reducing agent. The formation of gold shell on magnetic nanoparticles was confirmed by X-ray diffraction (XRD) and UV-Visible spectroscopy. The core–shell nanoparticles (CSn) were conjugated with thiolated pectin to form a stable aqueous dispersion. The hydrodynamic size of thiolated pectin stabilized core–shell nanoparticles (TP-CSn) measured by Dynamic light scattering (DLS) was 160.5 nm with a poly dispersity index (PDI) of 0.302, whereas the mean particle size of TP-CSn calculated by high resolution transmission electron microscopy (HRTEM) was 10.8 ± 2.7 nm. The value of zeta potential for TP-CSn was −13.6 mV. There was a decrease in the value of saturation magnetization upon formation of the gold shell on magnetic nanoparticles. The amount of thiolated pectin bound to the surface of core–shell nanoparticles, calculated using Thermogravimetric analysis (TGA), was 6% of sample weight.
The magnetic powder patterns found on polished iron crystals (which may contain a few percent of silicon) have been studied more carefully by using a macroscopic model and by investigating the forces on the powder particles. Reasons are given for preferring one of two simple models to explain the patterns; some interesting implications of the proposed model are then considered. Experiments are described which indicate that the structures under discussion originate during the polishing operation, but that other than magnetic causes must be responsible for the remarkable regularity of the patterns.
We have synthesized hyaluronic acid-coated magnetic nanoparticles (HA-MNPs) to selectively collect and detect of leukemia cells (CCRF-CEM) in combination with quartz crystal microbalance (QCM) measurement. Based on the specific binding of HA with CD44 receptors overexpressed on cell surface, HA-MNPs were successfully employed for selectively extracting CCRF-CEM cells from the complex matrices including human plasma samples. The collection and detection conditions for CCRF-CEM cells were optimized. Under optimized conditions, a detection limit of 8 × 103 cells mL-1 was obtained. The HA-MNPs-based magnetic separation combined with sensitive QCM measurement provides a simple, rapid and economical method for collecting and detecting leukemia cells, and this method may have great potential for wider applications in biomedical research and clinical diagnostics.
Self-assembled pectin nanoparticles was prepared and evaluated for delivering the hydrophobic drug, honokiol (HK), to HepG2 cells. These hydrophobic drug-loaded nanoparticles were developed without using any surfactant and organic solvent. Hydroxypropyl-β-cyclodextrin (HCD) was used to fabricate an inclusion complex with HK (HKHCD) to increase the solubility of the drug and thus facilitate its encapsulation and dispersion in the pectin nanoparticles. Investigation of the in vitro release indicated that the drug-loaded nanoparticles exhibited a higher drug release rate than free honokiol and an effective sustained-release. Cytotoxicity, cell apoptosis and cellular uptake studies further confirmed that the pectin nanoparticles with galactose residues generated higher cytotoxicity than free honokiol on HepG2 cells which highly expressed asialoglycoprotein receptors (ASGR). Nevertheless, these findings were not observed in ASGR-negative A549 cells under similar condition. Therefore, pectin nanoparticles demonstrated a specific active targeting ability to ASGR-positive HepG2 cells and could be used as a potential drug carrier for treatment of liver-related tumors.
Magnetic hybrid colloidal particles can be characterized using various techniques and numerous tools leading generally
to particles size, size distribution, and electrokinetic properties. However, the chemical composition of these
hybrid particles can be estimated using thermal gravimetric analysis (TGA). More interestingly, the combination of
this quantitative technique with the magnetization measurement leads not only to chemical composition but also
to the overall polymerization conversion and more precisely to the polymerization conversion on the seed particles.
In fact, the TGA performed on dried magnetic particles leads to exact organic/inorganic chemical composition.
Regarding the magnetization, the amount of magnetic material can be deduced, and consequently, the amount of
non-magnetic material can be also estimated. Thus, TGA and magnetization measurements are considered as
complementary techniques for characterization of magnetic hybrid colloidal particles.
Oleic acid and stearic acid are similar surfactants which, however, lead respectively to stability and to precipitation of ferrofluid suspensions: to understand this, the forces between layers of oleic-like surfactants and between layers of stearic-like surfactants across a hexadecane (HD) medium were measured using a surface force balance (SFB). Separate measurements reveal that only the oleic layers are solvated by HD, while the SFB results reveal that for both surfactants a marked net attraction is present between the surfaces. Simple considerations based on these observations explain why, despite this attraction, ferrofluid dispersions are stabilized by oleic but not by stearic surfactants.
CD44 is implicated in the regulation of tumor growth and metastasis but the mechanism by which expression of different CD44 isoforms determines the rate of primary and secondary tumor growth remains unclear. In the present study we use a human melanoma transfected with wild-type and mutant forms of CD44 to determine which functional property of the CD44 molecule is critical in influencing tumor behavior. We show that expression of a wild-type CD44 isoform that binds hyaluronic acid augments the rapidity of tumor formation by melanoma cells in vivo, whereas expression of a CD44 mutant, which does not mediate cell attachment to hyaluronate, fails to do so. The importance of CD44-hyaluronate interaction in tumor development is underscored by the differential inhibitory effect of soluble wild-type and mutant CD44-Ig fusion proteins on melanoma growth in vivo. Whereas local administration of a mutant, nonhyaluronate binding, CD44-Ig fusion protein has no effect on subcutaneous melanoma growth in mice, infusion of wild-type CD44-Ig is shown to block tumor development. Taken together, these observations suggest that the tumor growth promoting property of CD44 is largely dependent on its ability to mediate cell attachment to hyaluronate.