Molybdesum selenide-based platelet-rich plasma containing carboxymethyl chitosan/polyvinyl pyrrolidone composite antioxidant hydrogels dressing promotes the wound healing.

Excess free radicals at the wound site can cause an inflammatory response, which is not conducive to wound healing. Hydrogels with antioxidant properties can prevent inflammatory storms by scavenging free radicals from the wound site and inhibiting the release of inflammatory factors. In this study, we prepared the carboxymethyl chitosan (CMCS)/polyvinyl pyrrolidone (PVP)/Molybdenum (IV) Selenide (MoSe2), and platelet-rich plasma (PRP) (CMCS/PVP/MoSe2/PRP) hydrogels for accelerating the repair of wounds. In the hydrogels, the MoSe2 can scavenge various free radicals to reduce oxidative stress at the site of inflammation, endowed the hydrogels with antioxidant properties. Interestingly, growth factors released by PRP assisted the tissue repair by promoting the formation of new capillaries. CMCS as a backbone not only showed good biocompatibility and biodegradability but also played a significant role in maintaining the sustained release of growth factors. In addition, incorporating PVP enhanced the tissue adhesion and mechanical properties. The multifunctional composite antioxidant hydrogels have good swelling properties and biodegradability, which is completely degraded within 28 days. Thus, the antioxidant CMCS/PVP/MoSe2/PRP hydrogels provide a new idea for designing ideal multifunctional wound dressings.

Cd(II)-based complex loaded with drug doxorubicin hydrogels against leukemia and reinforcement learning.

A new 3D metal-organic frameworks [Cd6(L)4(bipy)3(H2O)2·H2O] (1) was gained by employing Cd(II) and organic ligand [H3L = 4,4',4''-(benzene-1,3,5-triyltris(oxy))tribenzoic acid)benzene acid; bipy = 4,4'-bipyridine] in the solvothermal condition, which has been fully examined via single-X ray diffraction, FTIR and elemental analysis and so on. Using natural polysaccharides hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) as raw materials, we successfully prepared HA/CMCS hydrogels and observed their internal micromorphology by scanning electron microscopy. Using doxorubicin (Dox) as a drug model, we synthesized a novel metal gel particle loaded with doxorubicin, and their encapsulation and release effects were studied using fluorescence spectroscopy, followed by further investigation of their components through thermogravimetric analysis. Based on this, the therapeutic effect on leukemia was evaluated. Finally, an enhanced learning method for automatically designing new ligand structures from host ligands was proposed. Through generative modeling and molecular docking simulations, the biological behavior of the host and predicted cadmium complexes was extensively studied.

Fish oil-loaded multicore submillimeter-sized capsules prepared with monoaxial electrospraying, chitosan-tripolyphosphate ionotropic gelation, and Tween blending.

In order to load fish oil for potential encapsulation of fat-soluble functional active substances, fish oil-loaded multicore submillimeter-sized capsules were prepared with a combination method of three strategies (monoaxial electrospraying, chitosan-tripolyphosphate ionotropic gelation, and Tween blending). The chitosan-tripolyphosphate/Tween (20, 40, 60, and 80) capsules had smaller and evener fish oil cores than the chitosan-tripolyphosphate capsules, which resulted from that Tween addition induced smaller and evener fish oil droplets in the emulsions. Tween addition decreased the water contents from 56.6 % to 35.0 %-43.4 %, increased the loading capacities from 10.4 % to 12.7 %-17.2 %, and increased encapsulation efficiencies from 97.4 % to 97.8 %-99.1 %. In addition, Tween addition also decreased the highest peroxide values from 417 meq/kg oil to 173-262 meq/kg oil. These properties' changes might result from the structural differences between the chitosan-tripolyphosphate and chitosan-tripolyphosphate/Tween capsules. All the results suggested that the obtained chitosan-tripolyphosphate/Tween capsules are promising carriers for fish oil encapsulation. This work also provided useful knowledge to understand the preparation, structural, and physicochemical properties of the chitosan-tripolyphosphate capsules.

Preparation of pH-sensitive carboxymethyl chitosan nanoparticles loaded with ginsenoside Rb1 and evaluation of drug release in vitro.

Oral absorption of ginsenoside Rb1 (Rb1) is often hindered by the gastrointestinal tract. Carboxymethyl chitosan deoxycholic acid loaded with ginsenoside Rb1 nanoparticles (CMDA@Rb1-NPs), were prepared as a delivery system using a self-assembly technique with amphipathic deoxycholic acid grafted carboxymethyl chitosan as the carrier, which improved the stability and embedding rate of Rb1. In addition, the CMDA@Rb1-NPs was encapsulated with sodium alginate by ion crosslinking method with additional layer (CMDAlg@Rb1-NPs). Scanning electron microscopy showed that the nanoparticles were spherical, evenly distributed, smooth and without obvious adhesion. By evaluating drug loading, entrapment efficiency, the encapsulation efficiency of Rb1 increased from 60.07 % to 72.14 % after grafting deoxycholic acid improvement and optimization. In vitro release results showed that the cumulative release of Rb1 by CMDAlg-NPs showed a pH dependent effect, which was <10 % in simulated gastric juice with pH 1.2, completely released with pH 7.4 for about 48 h. In addition, Rb1 and CMDAlg@Rb1-NPs had inhibitory effects on A549 cells, and the inhibitory effect of CMDAlg@Rb1-NPs was better. Therefore, all results indicated that CMDA/Alg@Rb1 nanoparticles might be a novel drug delivery system to improve the stability and embedding rate of Rb1, and has the potential to be applied in oral pharmaceutical preparations.

Synergistic stabilization of garlic essential oil nanoemulsions by carboxymethyl chitosan/Tween 80 and application for coating preservation of chilled fresh pork.

Garlic essential oil (GEO) is a potential natural antioxidant and antimicrobial agent for food preservation, but its intrinsic low water-solubility, high volatility and poor stability severely limit its application and promotion. In this work, we investigated the synergistic stabilization of the GEO-in-water nanoemulsion using carboxymethyl chitosan (CCS) and Tween 80 (TW 80). Additionally, the nanoemulsion was fabricated through high-pressure microfluidization and utilized for the coating-mediated preservation of chilled pork. The garlic essential oil nanoemulsion (GEON) with 3.0 % CCS and 3.0 % TW 80 exhibited more homogeneous droplet size (around 150 nm) and narrower size distribution, while maintained long-term stability with no significant change in size during 30 d storage. Compared with free GEO, the GEONs exhibited a higher scavenging capacity to DPPH and ABTS free radicals as well as higher inhibitory effects against Escherichia coli and Staphylococcus aureus, suggesting that the encapsulation of GEO in nanoemulsion considerably improved its antioxidant and antibacterial activities. Furthermore, the results of coating preservation experiments showed that the GEON coating effectively expanded the shelf-life of chilled fresh pork for approximately one week. Altogether, this study would guide the development of GEO-loaded nanoemulsions, and promote GEON as a promising alternative for coating preservation of chilled fresh meat.

Anticancer potential of thiocolchicoside and lauric acid loaded chitosan nanogel against oral cancer cell lines: a comprehensive study.

The present study explored the anticancer activity of a Chitosan-based nanogel incorporating thiocolchicoside and lauric acid (CTL) against oral cancer cell lines (KB-1). Cell viability, AO/EtBr dual staining and Cell cycle analysis were done to evaluate the impact of CTL nanogel on oral cancer cells. Real-time PCR was performed to analyze proapoptotic and antiapoptotic gene expression in CTL-treated KB-1 cells. Further, molecular docking analysis was conducted to explore the interaction of our key ingredient, thiocolchicoside and its binding affinities. The CTL nanogel demonstrated potent anticancer activity by inhibiting oral cancer cell proliferation and inducing cell cycle arrest in cancer cells. Gene expression analysis indicated alterations in Bax and Bcl-2 genes; CTL nanogel treatment increased Bax mRNA expression and inhibited the Bcl-2 mRNA expression, which showed potential mechanisms of the CTL nanogel's anticancer action. It was found that thiocolchicoside can stabilize the protein's function or restore it as a tumour suppressor. The CTL nanogel exhibited excellent cytotoxicity and potent anticancer effects, making it a potential candidate for non-toxic chemotherapy in cancer nanomedicine. Furthermore, the nanogel's ability to modulate proapoptotic gene expression highlights its potential for targeted cancer therapy. This research contributes to the growing interest in Chitosan-based nanogels and their potential applications in cancer treatment.

Carboxymethyl Chitosan-Coated Cyanidin-3-O-Glucoside-Beared Nanonutriosomes Suppress Palmitic Acid-Induced Hepatocytes Injury.

Cyanidin-3-O-glucoside (C3G) is classified as an anthocyanin (ACN) and is recognized for its remarkable antioxidant properties. Yet, the inadequate physicochemical stability of C3G restricts its potential for various biological applications. Thus, in this study, carboxymethyl chitosan (CMC)-coated nanonutriosomes (NS) were synthesized as a novel carrier for encapsulating C3G (CMC-C3G-NS) to improve C3G stability. CMC-C3G-NS exhibited a diameter of less than 200 nm along with an encouraging encapsulation efficiency exceeding 90%. Notably, the formulated CMC-C3G-NS possessed better stability under various pH, ionic, and oxygen conditions, improved controlled release properties, and higher hepatocellular uptake than uncoated particles (C3G-NS), indicating a longer retention time of C3G in a physiological environment. Of utmost significance, CMC-C3G-NS demonstrated superior alleviating effects against palmitic acid (PA)-induced oxidative hepatic damage compared to C3G-NS. Our study provided promising nanocarriers with the potential to deliver hydrophilic ACNs and controlled release properties for PA-induced hepatotoxicity alleviation.

Antibacterial conductive polyacrylamide/quaternary ammonium chitosan hydrogel for electromagnetic interference shielding and strain sensing.

The utilization of biomass-based conductive polymer hydrogels in wearable electronics holds great promise for advancing performance and sustainability. An interpenetrating network of polyacrylamide/2-hydroxypropyltrimethyl ammonium chloride chitosan (PAM/HACC) was firstly obtained through thermal-initiation polymerization of AM monomers in the presence of HACC. The positively charged groups on HACC provide strong electrostatic interactions and hydrogen bonding with the PAM polymer chains, leading to improved mechanical strength and stability of the hydrogel network. Subsequently, the PAM/HACC networks served as the skeletons for the in-situ polymerization of polypyrrole (PPy), and then the resulting conductive hydrogel demonstrated stable electromagnetic shielding performance (40 dB), high sensitivity for strain sensing (gauge factor = 2.56). Moreover, the incorporation of quaternary ammonium chitosan into PAM hydrogels enhances their antimicrobial activity, making them more suitable for applications in bacterial contamination or low-temperature environments. This conductive hydrogel, with its versatility and excellent mechanical properties, shows great potential in applications such as electronic skin and flexible/wearable electronics.

A Cellulose/Chitosan Dual Cross-Linked Multifunctional and Resilient Hydrogel for Emergent Open Wound Management.

Adhesive hydrogel holds huge potential in biomedical applications, such as hemostasis and emergent wound management during outpatient treatment or surgery. However, most adhesive hydrogels underperform to offer robust adhesions on the wet tissue, increasing the risk of hemorrhage and reducing the fault tolerance of surgery. To address this issue, this work develops a polysaccharide-based bioadhesive hydrogel tape (ACAN) consisting of dual cross-linking of allyl cellulose (AC) and carboxymethyl chitosan (CMCS). The hygroscopicity of AC and CMCS networks enables ACAN to remove interfacial water from the tissue surface and initializes a physical cross-link instantly. Subsequently, covalent cross-links are developed with amine moieties to sustain long-term and robust adhesion. The dual cross-linked ACAN also has good cytocompatibility with controllable mechanical properties matching to the tissue, where the addition of CMCS provides remarkable antibacterial properties and hemostatic capability. Moreover, compared with commercially available 3 M film, ACAN provides an ultrafast wound healing on tissue. The ACAN hybrid hydrogels have advantages such as biocompatibility and antibacterial, hemostatic, and wound healing properties, shedding new light on first-aid tape design and advancing the cellulose-based materials technology for high-performance biomedical applications.

N, O-carboxymethyl chitosan/oxidized cellulose composite sponge containing ε-poly-l-lysine as a potential wound dressing for the prevention and treatment of postoperative adhesion.

Herein, we designed and fabricated a biodegradable composite sponge which main component contained N, O-carboxymethyl chitosan (N,O-CS) and oxidized cellulose nanocrystals (TOCN) as a potential wound dressing for the prevention and treatment of postoperative adhesion. In order to improve antimicrobial properties of N,O-CS/TOCN composite sponges, natural antimicrobial agents (ε-Poly-l-Lysine，EPL) were successfully introduced and the EPL/N,O-CS/TOCN composite sponge exhibited excellent antibacterial properties and biological security. The EPL/N,O-CS/TOCN composite sponge can be degraded in vivo within 3 weeks. Finally, we analyzed the anti-adhesion performance of EPL/N,O-CS/TOCN composite sponge through a rat model of sidewall defect-cecum abrasion. These results demonstrated that EPL/N,O-CS/TOCN-treated group can effectively reduce the peritoneal adhesion formation than the commercial soluble gauze group and normal saline group, which mainly attribute to the excellent hemostatic function and tissue repair function of EPL/N,O-CS/TOCN composite sponge. It is believed that the EPL/N,O-CS/TOCN composite sponge will prove to be as a new medical device treat the internal tissue/organ repair and simultaneous prevention of postoperative adhesion.

Mannose-anchored quaternized chitosan/thiolated carboxymethyl chitosan composite NPs as mucoadhesive carrier for drug delivery.

There are various challenges for the mucosal delivery of drug, which is largely attributed to the absence of effective drug carriers that can make delivery to mucosal sites. In the present study, we aimed to synthesize bifunctional mucoadhesive nanoparticles (NPs) that could be used for mucosal delivery. N-2-Hydroxypropyl trimethyl ammonium chloride chitosan (M-N-2-HACC) was modified with D-mannose, and N-acetyl-L-cysteine (NAC) was immobilized on the carboxymethyl chitosan (N-CMCS). The electrostatic interaction between the two substances was used to produce mannose-modified thiolated chitosan NPs (M-N-2-HACC/N-CMCS NPs). The NPs showed a particle size of 196.72 ± 0.45 nm and zeta potential of 17.12 ± 0.50 mV. Moreover, it demonstrated high hydrophilicity, enduring drug release, stability, safety, and mucosal adhesion, which contributed to the effectiveness of mucosal administration. Additionally, the NPs could be instantly absorbed by macrophages. Collectively, these results suggested that M-N-2-HACC/N-CMCS NPs could be used as a promising candidate for mucosal delivery.

Preparation, biocompatibility, and wound healing effects of O-carboxymethyl chitosan nonwoven fabrics in partial-thickness burn model.

This study was aimed at preparing O-carboxymethyl chitosan (CM-CTS) fabrics, and examining the wound healing effects on partial-thickness burn. The functional polysaccharides were produced from chitosan needle-punched nonwovens reacted with chloroacetic acid. Then the biocompatibility and biological functions were evaluated through fibroblast L-929 and SD rats. CM-CTS fabrics were obtained with elongation at break more than 42%, tensile strength reaching 0.65 N/mm2, and water vapor transmission rate about 2600 g/m2∙24 h. Moreover, CM-CTS fabrics could effectively promote the mouse L-929 migration in vitro. CM-CTS fabrics yielded satisfactory results in angiogenesis, collagen deposition, interleukin-6 content, transforming growth factor level and healing rate, which were superior to the positive control and model groups after rats suffering with partial-thickness burn. In conclusion, CM-CTS fabrics possessed proper mechanical properties, air permeability, favorable biocompatibility, acceleration on fibroblasts migration and healing capacity for partial-thickness burn injury, and owned good potential as high-quality wound dressing.

Antimicrobial peptides/ciprofloxacin-loaded O-carboxymethyl chitosan/self-assembling peptides hydrogel dressing with sustained-release effect for enhanced anti-bacterial infection and wound healing.

Bacteria-induced wound infections and multifunctional hydrogels have received widespread attention in wound repair. In this study, self-assembling peptides (SAPs) were grafted on O-carboxymethyl chitosan (O-CMCS), and compact spatial structure and good drug sustained-release effect on mel-d1, a new AMP designed based on melittin with the same antimicrobial activity but lower cytotoxicity and ciprofloxacin (CIP) were obtained. In vivo test showed that the O-CMCS/SAP hydrogel loaded with CIP and mel-d1 accelerated the wound closure speed caused by infection of Escherichia coli and skin tissue regeneration. Both of the enhanced interaction between O-CMCS/SAP and CIP/Mel-d1 because of the hydrophobic interaction and π-π stacking, and the potential tissue healing ability of SAP played important roles. This study provided a rational design method of O-CMCS by grafting SAPs to give a wider range of biological functions.

Utilizing RNA nanotechnology to construct negatively charged and ultrasound-responsive nanodroplets for targeted delivery of siRNA.

Ultrasound nanodroplets (NDs) have been reported as a promising nanocarrier for siRNA delivery depending on its unique strengths of sonoporation. Presently, common means for NDs-mediated siRNA delivery is through electrostatic interaction, but challenges like cationic toxicity still exist. In this study, we demonstrated a novel strategy to construct negatively charged and ultrasound (US)-responsive O-carboxymethyl chitosan (O-CMS) NDs as a siRNA targeted delivery system through three-way junction of bacteriophage phi29 DNA packaging motor (3WJ-pRNA) nanotechnology. 39nt A10-3.2 aptamer targeting prostate specific membrane antigen (PSMA) and 21nt siRNA against cationic amino acid transporter 1 (siCAT-1) were annealed to 3WJ-pRNA scaffold via complementation with an extended sequence. The cholesterol molecule attached to one branch facilitates the 3WJ-pRNA nanoparticles anchoring onto NDs. The desired O-CMS NDs with siRNA-loading and RNA-aptamer modification (A10-3.2/siCAT-1/3WJ-NDs) were successfully prepared, which were with spherical shapes, core-shell structures and uniform in sizes (198 nm with PDI 0.3). As a main proportion of shell, O-CMC showed a certain anti-tumor effects. In vitro studies demonstrated that A10-3.2/siCAT-1/3WJ-NDs exhibited good contrast-enhanced US imaging, buffering capacity and high bio-safety, were able to deliver siCAT-1 to PSMA-overexpressed prostate cancer cells under US irradiation, thus silence the CAT-1 expression, and consequently suppressing 22RV1 cell proliferation and migration. Taken overall, our findings provide a promising strategy to develop negatively charged and US-responsive NDs for tumor-targeted siRNA delivery.

Improved myocardial performance in infarcted rat heart by injection of disulfide-cross-linked chitosan hydrogels loaded with basic fibroblast growth factor.

Myocardial infarction (MI) has been considered as the leading cause of cardiovascular-related deaths worldwide. Basic fibroblast growth factor (bFGF) is a member of the fibroblast growth factor family that promotes angiogenesis after MI; however, it has poor clinical efficacy due to proteolytic degradation, low drug accumulation, and severe drug-induced side effects. In this study, an injectable disulfide-cross-linked chitosan hydrogel loaded with bFGF was prepared via a thiol-disulfide exchange reaction for MI treatment. The thiol-disulfide exchange reaction between pyridyl disulfide-modified carboxymethyl chitosan (CMCS-S-S-Py) and reduced BSA (rBSA) was carried out under physiological conditions (37 °C and pH 7.4). The mechanical properties of the disulfide-cross-linked chitosan hydrogel were evaluated based on the molar ratio of the pyridyl disulfide groups of CMCS-S-S-Py and the thiol groups of rBSA. The disulfide-cross-linked chitosan hydrogel showed good swelling performance, rapid glutathione-triggered degradation behavior and well-defined cell proliferation towards NIH 3T3 fibroblast cells. In the process of establishing a rat MI model, the squeezing heart method was used to make the operation more accurate and the mortality of rats was decreased by using a ventilator. The disulfide-cross-linked chitosan hydrogel loaded with bFGF (bFGF-hydrogel) was injected into a peri-infarcted area of cardiac tissue immediately following MI. Echocardiography demonstrated that the left ventricular functions were improved by the bFGF-hydrogel after 28 days of treatment. Histological results revealed that the hydrogel significantly reduced the fibrotic area of MI, and this was further improved by the bFGF-hydrogel treatment. TUNEL and immunohistochemical staining results showed that the bFGF-hydrogel had a more synergistic effect on antiapoptosis and proangiogenesis than using either bFGF or the hydrogel alone.

Zingiber officinale essential oil-loaded chitosan-tripolyphosphate nanoparticles: Fabrication, characterization and in-vitro antioxidant and antibacterial activities.

Zingiber officinale essential oil (ZEO) was encapsulated in chitosan nanoparticles at different concentrations using the emulsion-ionic gelation technique and its antioxidant and antibacterial effects were investigated. The results indicated that ZEO level had a significant effect on encapsulation efficiency (EE), loading capacity (LC), particle size and zeta potential. The value obtained for EE, LC, mean particle size and zeta potential were 49.11%-68.32%, 21.16%-27.54%, 198.13-318.26 nm and +21.31-43.57 mV, respectively. According to scanning electron micrographs, the nanoparticles had a spherical shape with some invaginations due to the drying process. The presence of essential oil within the chitosan nanoparticles was confirmed by Fourier transform infrared (FTIR) spectroscopy. In vitro release studies in simulated gastrointestinal fluid (SGF) and simulated intestinal fluid (SIF) indicated an initial burst effect followed by slow release with higher release rate in acidic medium of SGF. ZEO-loaded nanoparticles showed DPPH radical scavenging activity of 20%-61% which increased by raising the ZEO level. Moreover, results of antibacterial activity revealed that Staphylococcus aureus (with inhibition zones of 19-35.19 mm2) and Salmonella typhimurium (with inhibition zones of 9.78-17.48 mm2) were the most sensitive and resistant bacteria to ZEO, respectively. Overall, chitosan nanoparticles can be considered as suitable vehicles for ZEO and improve its stability and solubility.

Polyethylenimine grafted-chitosan based Gambogic acid copolymers for targeting cancer cells overexpressing transferrin receptors.

Recent advancements in gene delivery systems that specifically target a variety of cancer types have increased demand for tissue-specific gene therapy. The current study describes the synthesis of a copolymer (GPgWSC) composed of a polyethylenimine (PEI)-grafted water-soluble chitosan (WSC) and gambogic acid (GA). It was validated as a ligand capable of enabling targeted attachment to transferrin receptors in HCT116 cancer cell lines. GPgWSC demonstrated superior antitumor activity in vitro in HCT116 compared to LoVo or MCF-7 cell lines, facilitated by the apoptotic activity of psiRNA-hBCL2. Pre-incubation of transferrin significantly inhibited GFP expression in the GPgWSC polyplex, demonstrating that GA is an extremely effective transferrin receptor targeting molecule. Additionally, in the HCT116-bearing mouse model, the tumor mass of PBS-treated mice increased to 2270 mm2 after 22 days, but the injection of GPgWSC polyplex significantly reduced the mass-increasing rate as a mass size of 248 mm2.

Preparation and synergistic chemo-photothermal therapy of redox-responsive carboxymethyl cellulose/chitosan complex nanoparticles.

Chemo-photothermal combination therapy has great promise for enhanced tumor treatment. Hereby, we developed a complex nanoparticle using electrostatic absorption method, in which the inner chitosan (CS) NPs loaded polypyrrole (PPy) nanoparticles and 5-fluorouracil (5Fu), the outer shell was carboxymethyl cellulose (CMC) crosslinked with disulfide. The drug loaded polysaccharide complex nanoparticles displayed good photothermal effects, and the drug release would be triggered by multi-model response of NIR irradiation, high glutathione (GSH) and weak acidity in tumor environment. In vitro biological studies indicated the nanopartiles could be effectively internalized by HepG2 cancer cells. Moreover, the remarkable inhibition of the CMC complex PPy and 5Fu loaded CS nanoparticles (CMC/CS@PPy + 5Fu NPs) against tumor growth was achieved in HepG2-bearing mice model, suggesting its great potential for synergetic chemo-photothermal therapy.

O-carboxymethyl chitosan based pH/hypoxia-responsive micelles relieve hypoxia and induce ROS in tumor microenvironment.

The hypoxia in tumor microenvironment (TME) can upregulate the HIF-1α and PD-L1 expression and cause immunosuppression of tumor. In this study, a carboxymethyl chitosan-based pH/hypoxia-responsive and γ-Fe2O3/isosorbide dinitrate carrying micelle was designed, and it could catalyze endogenous H2O2 to generate oxygen and relieve hypoxia in TME, so as to relieve the overexpression of HIF-1α and PD-L1 in tumor; meanwhile, it could react with H2O2 to release ROS via Fenton reaction and induce cytotoxicity in tumor. Along with these multiple effects, this carboxymethyl chitosan-based micelles could provide a comprehensive strategy for tumor treatment.

Stimuli-Responsive Drug Delivery of Doxorubicin Using Magnetic Nanoparticle Conjugated Poly(ethylene glycol)-g-Chitosan Copolymer.

Stimuli-responsive nanoparticles are regarded as an ideal candidate for anticancer drug targeting. We synthesized glutathione (GSH) and magnetic-sensitive nanocomposites for a dual-targeting strategy. To achieve this goal, methoxy poly (ethylene glycol) (MePEG) was grafted to water-soluble chitosan (abbreviated as ChitoPEG). Then doxorubicin (DOX) was conjugated to the backbone of chitosan via disulfide linkage. Iron oxide (IO) magnetic nanoparticles were also conjugated to the backbone of chitosan to provide magnetic sensitivity. In morphological observation, images from a transmission electron microscope (TEM) showed that IO nanoparticles were embedded in the ChitoPEG/DOX/IO nanocomposites. In a drug release study, GSH addition accelerated DOX release rate from nanocomposites, indicating that nanocomposites have redox-responsiveness. Furthermore, external magnetic stimulus concentrated nanocomposites in the magnetic field and then provided efficient internalization of nanocomposites into cancer cells in cell culture experiments. In an animal study with CT26 cell-bearing mice, nanocomposites showed superior magnetic sensitivity and then preferentially targeted tumor tissues in the field of external magnetic stimulus. Nanocomposites composed of ChitoPEG/DOX/IO nanoparticle conjugates have excellent anticancer drug targeting properties.