Supramolecular Nanozyme System Based on Polydopamine and Polyoxometalate for Photothermal-Enhanced Multienzyme Cascade Catalytic Tumor Therapy.

The advent of enzyme-facilitated cascade events in which endogenous substrates within the human body are used to generate reactive oxygen species (ROS) has spawned novel cancer treatment possibilities. In this study, a supramolecular cascade catalytic nanozyme system was successfully developed, exhibiting photothermal-enhanced multienzyme cascade catalytic and glutathione (GSH) depletion activities and ultimately triggering the apoptosis-ferroptosis synergistic tumor therapy. The nanozyme system was fabricated using ß-cyclodextrin-functionalized polydopamine (PDA) as the substrate, which was then entangled with polyoxometalate (POM) via electrostatic forces and assembled with adamantane-grafted hyaluronic acid and glucose oxidase (GOx) via host-guest supramolecular interaction for tumor targeting and GOx loading. The catalytic function of GOx facilitates the conversion of glucose to H2O2 and gluconic acid. In turn, this process affirms the propitious generation of hydroxyl radical (•OH) through the POM-mediated cascade catalysis. Additionally, the POM species actively deplete the intracellular GSH pool, initiating a cascade catalytic tumor therapy. In addition, the PDA-POM-mediated photothermal hyperthermia boosted the cascade catalytic effect and increased ROS production. This confers considerable promise for photothermal therapy (PTT)/nanocatalytic cancer therapy on supramolecular nanozyme systems. The in vitro and in vivo antitumor efficacy studies demonstrated that the supramolecular cascade catalytic nanozyme system was effective at reducing tumor development while maintaining an acceptable level of biocompatibility. Henceforth, this study is to widen the scope of cascade catalytic nanoenzyme production using supramolecular techniques, as well as endeavor to delineate a prospective pathway for the application of PTT-enhanced nanocatalytic tumor therapy.

Multifunctional chitosan/alginate hydrogel incorporated with bioactive glass nanocomposites enabling photothermal and nitric oxide release activities for bacteria-infected wound healing.

It is highly desirable to develop novel multifunctional wound dressing materials capable of delivering active molecules capable of resolving bacterial infections and replenishment of appropriate growth factors for bacteria-infected wound healing. Polysaccharides have numerous biomedical benefits and have been widely used to construct biomaterial scaffolds. Herein, multifunctional chitosan/alginate hydrogel decorated with ß-cyclodextrin (ß-CD) modified polydopamine (PDA)-bioactive glass (BG) nanoparticles (NPs) integrating photothermal performance and nitric-oxide release activities for the treatment of bacterially infected wounds is presented. As the NO precursor N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine (BNN6) encapsulated into the hydrophobic cavity of ß-CD on the PDA-coated BG NPs, the resultant NO@CD-PDA/BG NPs, are imparted with the feature of NIR triggered NO release and desired PTT/NO synergetic antibacterial effects. Furthermore, the release of NO, Ca, and Si ions from the NO@CD-PDA/BG NPs, has the benefit of regulating inflammation, promoting fibroblast proliferation, and stimulating angiogenesis. Besides, the chitosan/alginate hydrogel scaffolds provided a suitable microenvironment to accelerate wound healing. By applying the multifunctional chitosan/alginate nanocomposite hydrogel to S. aureus-infected full-thickness skin defect mouse model, the authors demonstrated that chitosan/alginate nanocomposite hydrogel has multiple functions in preventing bacterial infections, accelerating angiogenesis and wound regeneration, indicating promising application in wound healing.

Hybrid Ag nanoparticles/polyoxometalate-polydopamine nano-flowers loaded chitosan/gelatin hydrogel scaffolds with synergistic photothermal/chemodynamic/Ag+ anti-bacterial action for accelerated wound healing.

Bacterial infections significantly slow the wound healing process, thus severely threatening human health. Furthermore, traditional antibiotics may promote the development of multidrug-resistant bacteria. Therefore, developing novel bactericides and therapeutic strategies for bacterial infections is important to enhance wound healing. Herein, a three-in-one bactericidal flower-like nanocomposite was assembled using Ag nanoparticles/phosphotungstic acid-polydopamine nano-flowers (AgNPs/POM-PDA). The nanocomposite exhibited photothermal therapy (PTT) when exposed to NIR light via photothermal conversion by PDA. The resultant photothermal effect accelerated and controlled the Ag+ released from AgNPs. The chemodynamic therapy (CDT) was obtained via POM catalytic Fenton-like reaction. The combined PTT/CDT/Ag+ treatment achieved excellent synergistic anti-bacterial activity against both gram-negative E. coli and gram-positive S. aureus. A multifunctional wound dressing was then obtained by embedding the AgNPs/POM-PDA flower-like nanocomposite into the chitosan (CS)/gelatin (GE) biocomposite hydrogel. The synergy of AgNPs/POM-PDA nanocomposites and CS/GE hydrogel remarkably accelerated wound healing in vivo due to the excellent biocompatibility, hydroabsorptivity, and breathability of the hydrogel. In this study, a multifunctional agent was developed to synergistically combat bacterial infections and accelerate wound healing.

Co-loaded lapatinib/PAB by ferritin nanoparticles eliminated ECM-detached cluster cells via modulating EGFR in triple-negative breast cancer.

Cancer stem cell (CSC) cluster of triple-negative breast cancer (TNBC) is suggested to be responsible for therapy resistance, metastatic process and cancer recurrence, yet the sensitivity of CSC clusters of TNBC to ferroptosis remains elusive in a great measure. Current research revealed that epidermal growth factor receptor (EGFR) reinforced CD44-mediated TNBC cell clustering, whether blockade of EGFR has synergistic effects on erastin-induced tumor inhibition of CSC clusters is still poorly understood. Here, we found that fraction of CD24lowCD44high cells and size of tumor spheres clearly decreased following EGFR inhibition in TNBC cells. Inhibition of EGFR promoted expression of LC3B-II via YAP/mTOR signaling pathway, indicating that EGFR-mediated autophagy which contributed to ferroptosis. In order to further verify the protective effects of EGFR on ferroptosis induced by small molecules in TNBC cells, pseudolaric acid B (PAB) which led to ferroptosis of malignant cells was selected. In our experiment, lapatinib and PAB cotreatment inhibited TNBC cells viability and restrained formation of tumor spheres, accompanied with a high level of intracellular ROS. To target delivery lapatinib and PAB to TNBC cells, lapatinib/PAB@Ferritin (L/P@Ferritin) nanoparticles were prepared; results of in vitro and in vivo showed a higher tumor suppression efficiency of L/P@Ferritin, highlighting that it might provide a new perspective for treatment of CSC clusters of TNBC.

S-nitrosoglutathione functionalized polydopamine nanoparticles incorporated into chitosan/gelatin hydrogel films with NIR-controlled photothermal/NO-releasing therapy for enhanced wound healing.

Nitric oxide (NO) has aroused wide interest in the treating infected wounds due to its characteristic functionalities. However, its utilization is limited due to its volatile properties, high reactivity, direct potential toxicity, and byproducts of NO donors limited its application. Herein, endogenously NO donor S-nitrosoglutathione (GSNO) was connected covalently to polydopamine nanoparticles (PDA-GSNO NPs) to minimize the loss of NO in aqueous medium. Meanwhile, near-infrared (NIR)-controlled NO release and photothermal therapy (PTT) was obtained through the photothermal conversion by PDA. Then chitosan (CS)/gelatin (GE) biocomposite hydrogel films with preferable biocompatibility, surface hydrophilicity, hydroabsorptivity, and mechanical adhesive properties were constructed. By embedding PDA-GSNO NPs into the films, a multifunctional wound dressing was fabricated. Under NIR light irradiation, the combination of PTT, NO-releasing, and CS antibacterial agents can strengthen the in vitro antimicrobial efficacy and in vivo wound healing activities. Meanwhile, the obtained wound dressing presented good biocompatibility. This work outlines an approach for combating bacterial infections and demonstrating the possibility for synergistic NO-releasing wound healing.

Fabrication and Characterization of Chitosan/Poly(Lactic-Co-glycolic Acid) Core-Shell Nanoparticles by Coaxial Electrospray Technology for Dual Delivery of Natamycin and Clotrimazole.

Natamycin (NAT) is the drug of choice for the treatment of fungal keratitis (FK). However, its inherent shortcomings, such as poor solubility, high dosing frequency, and long treatment cycle, need to be urgently addressed by designing a new delivery to widen its clinical utility. Growing research has confirmed that clotrimazole (CLZ) plays a significant role in fungal growth inhibition. Hence, coaxial electrospray (CO-ES) technology is used herein to prepare nano-systems with an average hydrodynamic particle size of 309-406 nm for the co-delivery of NAT and CLZ in chitosan (CTS) and poly(lactic-co-glycolic acid) (PLGA). The resulting NAT/CLZ@CTS/PLGA formulations were characterized by a transmission electron microscope (TEM) and in vitro release test. The results show that the formulations had obvious core-shell structures, uniform particle distribution, and also can sustain the release of drugs over 36 h. Furthermore, in vitro hemolysis, in vivo corneal irritation test, local allergenic test, and antifungal activity analyses are performed to evaluate the safety and efficiency of the formulations. Thus, good biosafety along with a significant anti-candidiasis effect are found in the NAT/CLZ@CTS/PLGA nanoparticles (NPs). Taken together, the results suggest that this design may provide a promising drug delivery system and a new option for the treatment of FK.

Fe(II) and Tannic Acid-Cloaked MOF as Carrier of Artemisinin for Supply of Ferrous Ions to Enhance Treatment of Triple-Negative Breast Cancer.

Suppression of tumor development by inducing ferroptosis may provide a potential remedy for triple-negative breast cancer, which is sensitive to intracellular oxidative imbalance. Recently, artemisinin (ART) and its derivatives have been investigated as potential anticancer agents for the treatment of highly aggressive cancers via the induction of ferroptosis by iron-mediated cleavage of the endoperoxide bridge. Owing to its poor water solubility and limited intracellular iron content, it is challenging for further application in antitumor therapy. Herein, we developed ferrous-supply nano-carrier for ART based on tannic acid (TA) and ferrous ion (Fe(II)) coated on the zeolitic imidazolate framework-8 (ZIF) with ART encapsulated (TA-Fe/ART@ZIF) via coordination-driven self-assembly. Drug release experiments showed that ART was not nearly released in pH 7.4, while 59% ART was released in pH 5.0 after 10 h, demonstrating the excellent pH-triggered release. Meanwhile, a high level of intracellular ROS and MDA, accompanied with decreasing GSH and GPX4, displayed a newly developed nano-drug system displayed markedly enhanced ferroptosis. Compared with monotherapy, in vitro and vivo tumor inhibition experiments demonstrated higher efficiency of tumor suppression of TA-Fe/ART@ZIF. This work provides a novel approach to enhance the potency of ferroptotic nano-medicine and new directions for TBNC therapy.

Regulation of GSK3ß/Nrf2 signaling pathway modulated erastin-induced ferroptosis in breast cancer.

Ferroptosis is a newly discovered form of regulated cell death and characterized by an iron-dependent accumulation of lethal lipid reactive oxygen species (ROS), ferroptosis may exhibit a novel spectrum of clinical activity for cancer therapy. However, the significance of ferroptosis in the context of carcinoma biology is still emerging. Glycogen synthase kinase-3ß (GSK-3ß) has been found to be a fundamental element in weaking antioxidant cell defense by adjusting the nuclear factor erythroid 2-related factor 2 (Nrf2). In our study, decreased expression of GSK-3ß was observed in the cancer tissues of breast cancer patients, results of immunohistochemistry indicated that Nrf2 was highly expressed in low-GSK-3ß-expressed breast cancer tissues. The contributions of aberrant expression of GSK-3ß and Nrf2 to the erastin-induced ferroptosis in breast cancer were further assessed, silence of GSK-3ß blocked erastin-induced ferroptosis with less production of ROS and malondialdehyde (MDA) via upregulation of GPX4 and downregulation of arachidonate 15-lipoxygenase (Alox15), overexpression of GSK-3ß enhanced erastin-triggered ferroptosis with elevated ROS and MDA. Enhanced erastin-induced ferroptosis by overexpression of GSK-3ß was blocked by activating Nrf2. We further confirmed that overexpression of GSK-3ß strengthened erastin-induced tumor growth inhibition in breast cancer xenograft models in vivo. In summary, our findings conclude that modulation the balance between GSK-3ß/Nrf2 is a promising therapeutic approach and probably will be important targets to enhance the effect of erastin-induced ferroptosis in breast cancer.

Cyclodextrin-Modified CeO2 Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis.

PURPOSE: Reactive oxygen species (ROS)-induced oxidative stress plays a key role in the pathogenesis and progression of psoriasis by causing inflammation. Antioxidative strategies eradicating ROS may serve as effective and easy treatment options for psoriasis, while nanozymes with intrinsic antioxidant enzyme-like activity have not been explored for psoriasis treatment. The aim of this study is to fabricate ß-cyclodextrins (ß-CDs)-modified ceria nanoparticles (ß-CDs/CeO2 NPs) with drug-loaded and multimimic-enzyme activities for combinational psoriasis therapy. METHODS: The ß-CDs/CeO2 NPs were synthesized by a hydrothermal method using unmodified ß-CDs as a protecting agent. The structure, size and morphology were analyzed by dynamic light scattering, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy. Considering the superoxide dismutase (SOD)- and catalase-mimetic activities, the in vitro antioxidant activity of the ß-CDs/CeO2 NPs was investigated. After dithranol (DIT) was loaded, the drug-loading capacity and release profile were determined by UV-visible light spectrophotometer and high-performance liquid chromatography. The anti-psoriatic efficacy was studied in the imiquimod (IMQ)-induced mouse model on the basis of morphological evaluation, psoriasis area and severity index calculation (PASI), and inflammatory cytokine expression. RESULTS: The average particle size of the blank ß-CDs/CeO2 NPs was 60.89±0.32 nm with a polydispersity index (PDI) of 0.12, whereas that of the DIT-loaded NPs was 79.38±1.06 nm with a PDI of 0.27. TEM results showed the as-prepared NPs formed a uniform quasi-spherical shape with low polydispersity. XPS indicates synthesized NPs have a mixed Ce3+/Ce4+ valence state. FTIR spectroscopy confirmed the presence of ß-CDs and DIT in the NPs. Inhibition of superoxide anion rate by NPs could be reached to 79.4% in the presence of 200 µg/mL, and elimination of H2O2 efficiency reached about 50% in the presence of 40 µg/mL, demonstrating excellent superoxide dismutase- and catalase-mimicking activities, thereby providing remarkable cryoprotection against ROS-mediated damage. Furthermore, ß-CDs on the surface endowed the NPs with drug-loading function via host-guest interactions. The entrapment efficiency and drug loading of DIT are 94.7% and 3.48%, respectively. The in vitro drug release curves revealed a suitable release capability of DIT@ß-CDs/CeO2 NPs under physiological conditions. In IMQ-induced psoriatic model, the DIT@ß-CDs/CeO2 NPs exhibited excellent therapeutic effect. CONCLUSION: This study may pave the way for the application of nanozyme ß-CDs/CeO2 NPs as a powerful tool for psoriasis therapy.

Astragalus Polysaccharides/Chitosan Microspheres for Nasal Delivery: Preparation, Optimization, Characterization, and Pharmacodynamics.

Chitosan (CTS) constitutes a promising area in treatment of nose-related diseases as a nasal drug delivery carrier. Astragalus polysaccharide (APS) significantly attenuates eosinophils and neutrophil-dominant airway inflammation, and it has a potential pharmaceutical application in the treatment of severe asthma. The purpose of this work was to prepare APS/CTS microspheres intended for nasal drug delivery by the spray-drying method. The characteristics of APS/CTS microspheres were evaluated by a scanning electron microscope, Fourier transform infrared spectroscopy, differential scanning calorimetry, and in vitro drug release. The effect of APS/CTS microspheres on rats with allergic rhinitis (AR) was investigated by eosinophil and neutrophil counts in nasal lavage fluid. Results of SEM showed that microspheres were spherical and wrinkled. In vitro release showed that 67.48-93.76% APS was released from APS/CTS microspheres at pH 6.8 within 24 h. The effects showed that APS/CTS microspheres alleviated allergic symptoms and reduced eosinophils infiltration and the expression of interleukin-4 in the nasal mucosa tissue of rats that had no liver and kidney toxicity by hematoxylin-eosin staining observation. In conclusion, these results indicated that APS/CTS microspheres had excellent characteristics for the treatment of AR.

Acetaminophen sensitizing erastin-induced ferroptosis via modulation of Nrf2/heme oxygenase-1 signaling pathway in non-small-cell lung cancer.

Growing evidence confirms that ferroptosis plays an important role in tumor growth inhibition. However, some non-small-cell lung cancer (NSCLC) cell lines are less sensitive to erastin-induced ferroptotic cell death. Elucidating the mechanism of resistance of cancer cells to erastin-induced ferroptosis and increasing the sensitivity of cancer cells to erastin need to be addressed. In our experiment, erastin and acetaminophen (APAP) cotreatment inhibited NSCLC cell viability and promoted ferroptosis and apoptosis, accompanied with attenuation of glutathione and ectopic increases in lipid peroxides. Erastin and APAP promoted NSCLC cell death by regulating nucleus translocation of nuclear factor erythroid 2-related factor 2 (Nrf2); and the ferroptosis induced by erastin and APAP was abrogated by bardoxolone methyl (BM) with less generation of reactive oxygen species and malondialdehyde. As a downstream gene of Nrf2, heme oxygenase-1 expression decreased significantly with the cotreatment of erastin and APAP, which could be rescued by BM. In vivo experiment showed that the combination of erastin and APAP had a synergic therapeutic effect on xenograft of lung cancer. In short, the present study develops a new effective treatment for NSCLC by synergizing erastin and APAP to induce ferroptosis.

Targeted exosome-encapsulated erastin induced ferroptosis in triple negative breast cancer cells.

Ferroptosis is an iron-dependent, lipid peroxide-driven cell death caused by inhibition of the cystine/glutamate transporter, which is of importance for the survival of triple-negative breast cancer (TNBC) cells. Erastin is a low molecular weight chemotherapy drug that induces ferroptosis; however, poor water solubility and renal toxicity have limited its application. Exosomes, as drug delivery vehicles with low immunogenicity, high biocompatibility and high efficiency, have attracted increasing attention in recent years. Herein, we developed a formulation of erastin-loaded exosomes labeled with folate (FA) to form FA-vectorized exosomes loaded with erastin (erastin@FA-exo) to target TNBC cells with overexpression of FA receptors. The characterization, drug release, internalization and anti-tumor effect in vitro of erastin@FA-exo were determined. Erastin@FA-exo could increase the uptake efficiency of erastin into MDA-MB-231 cells; compared with erastin@exo and free erastin, erastin@FA-exo has a better inhibitory effect on the proliferation and migration of MDA-MB-231 cells. Furthermore, erastin@FA-exo promoted ferroptosis with intracellular depletion of glutathione and reactive oxygen species overgeneration. Western blot analyses revealed that erastin@FA-exo suppressed expression of glutathione peroxidase 4 (GPX4) and upregulated expression of cysteine dioxygenase (CDO1). We conclude that targeting and biocompatibility of exosome-based erastin preparations provide an innovative and powerful delivery platform for anti-cancer therapy.

Iron-Chelated Polydopamine Decorated Doxorubicin-Loaded Nanodevices for Reactive Oxygen Species Enhanced Cancer Combination Therapy.

Combination therapy which enhances efficacy and reduces toxicity, has been increasingly applied as a promising strategy for cancer therapy. Here, a reactive oxygen species (ROS) that enhanced combination chemotherapy nanodevices was fabricated based on the Fe-chelated polydopamine (PDA) nanoparticles (NPs). The structure was characterized by dynamic light scattering-autosizer, transmission electron microscopy, energy dispersive spectroscopy, and Fourier-transform infrared (FT-IR) spectrophotometer. The in vitro drug release profile triggered by low intracellular pH indicated that the system demonstrated controlled therapeutic activity. In vitro cell uptake studies showed that doxorubicin (DOX)-loaded Fe-PDA/ folic acid (FA)- polyethylene glycol (DOX@Fe-PDA/FA-PEG) had a strong uptake capacity and can be rapidly internalized by MCF-7 cells. The in vitro experiments demonstrated that DOX@Fe-PDA/FA-PEG triggered the intracellular ROS overproduction, thereby enhancing its therapeutic effect on breast cancer. In summary, this experiment demonstrated the novel DOX-loaded composite NPs used as a potential targeted nanocarrier for breast cancer treatment, which could be a promising therapeutic strategy against breast cancer.

Cold atmospheric plasma and iron oxide-based magnetic nanoparticles for synergetic lung cancer therapy.

Cold atmospheric plasma (CAP) is an emerging biomedical technique that shows great potential for cancer treatment. On the other hand, magnetic nanoparticles open up a wide field of possible applications in medicine. Here we seek to develop a novel dual cancer therapeutic method by integrating promising CAP and iron oxide-based magnetic nanoparticles (MNPs), and evaluate its underlying mechanism for targeted lung cancer treatment. For this purpose, the synergistic effects of CAP and iron oxide-based MNPs on cellular bioactivity, epidermal growth factor receptor (EGFR) expression, and EGFR downstream signaling pathways were investigated. Results showed that the effectiveness of CAP and iron oxide-based MNPs for synergistic strongly killed activity against lung cancer cells, and significantly inhibited cell proliferation via reduction of viability and induction of apoptosis. Importantly, CAP combining with iron oxide-based MNPs induced EGFR downregulation while CAP inhibited lung cancer cells via depressing pERK and pAKT. Translation of these findings to an in vivo setting demonstrates that CAP combining iron oxide-based MNPs is effective at preventing xenograft tumors. Thus, the integration of CAP and iron oxide-based MNPs provides a promising tool for the development of a new cancer treatment strategy.

Ruthenium-containing supramolecular nanoparticles based on bipyridine-modified cyclodextrin and adamantyl PEI with DNA condensation properties.

Exploring safe and highly efficient gene carriers made from biocompatible constituents has great prospects for clinical gene therapy. Here, a supramolecular gene delivery system was readily constructed by assembling adamantyl-modified polyethylenimine (PEI-Ada) units with a versatile ruthenium bipyridine-modified cyclodextrin (Ru-CD) through host-guest interactions. The photophysical and morphological features of the PEI-Ada@Ru-CD nanoparticles were systematically characterized by techniques including UV-vis absorption spectroscopy, fluorescence spectroscopy, transmission electron microscopy, dynamic light scattering, and zeta potential experiments. The small size and suitably positive zeta potential of the nanoparticles facilitated their cellular uptake and gene transfection. As expected, DNA interaction studies, which were performed using agarose gel electrophoresis and atomic force microscopy, showed that the ability of the nanoparticles to condense DNA was higher than that of the gold standard, i.e., PEI, at low N/P ratios. The design of these ruthenium-containing supramolecular nanoparticles based on bipyridine-modified cyclodextrin and adamantyl PEI has great prospects in the development of gene delivery vehicles.

Targeted p53 on Small-Molecules-Induced Ferroptosis in Cancers.

Ferroptosis is a type of programmed cell death characterized by the accumulation of lipid reactive oxygen species (L-ROS) driven by the oxidative degeneration of lipids in an iron-dependent manner. The mechanism by which lipid oxidative degradation drives ROS-ferroptosis involves metabolic dysfunctions that result in impaired intracellular metabolic processes and ROS production. Recent studies have found that p53 acts as a positive regulator of ferroptosis by promoting ROS production. p53 directly regulates the metabolic versatility of cells by favoring mitochondrial respiration, leading to ROS-mediated ferroptosis. In mild stress, p53 protects cell survival via eliminating ROS; additionally, in human colorectal cancer, p53 antagonizes ferroptosis by formation of the DPP4-p53 complex. In short, the mechanisms of p53-mediated ROS production underlying cellular response are poorly understood. In the context of recent research results, the indistinct roles of p53 on ROS-mediated ferroptosis are scrutinized to understand the mechanism underlying p53-mediated tumor suppression.

Paclitaxel-Loaded Core-Shell Magnetic Nanoparticles and Cold Atmospheric Plasma Inhibit Non-Small Cell Lung Cancer Growth.

Nanoparticle-based drug delivery allows effective and sustained delivery of therapeutic agents to solid tumors and has completely changed how cancer is treated. As a new technology for medical applications, cold atmospheric plasma (CAP) shows a great potential in selective cancer treatment. The aim of this work is to develop a new dual cancer treatment approach by integrating CAP with novel paclitaxel (PTX)-loaded nanoparticles for targeting A549 cells. For this purpose, PTX-loaded core-shell magnetic nanoparticles were prepared through coaxial electrospraying, and various characteristics were investigated. Biodegradable poly(lactic- co-glycolic acid) was selected as the polymer shell to encapsulate the anticancer therapeutics. Results demonstrated a uniform size distribution and high drug encapsulation efficiency of the electrosprayed nanoparticles, which had sustained release characteristics and a variety of excellent properties. An in vitro study showed that PTX-loaded nanoparticles and CAP synergistically inhibited the growth of A549 cells more effectively than when each was used individually. We also found that CAP could induce the PTX-loaded nanoparticles in tumor cells to increase the effective drug concentration to a level that might be conducive to reduce drug resistance. Therefore, the integration of PTX-encapsulated nanoparticles and CAP provides a promising tool for the development of a new non-small cell lung cancer treatment strategy.

The Evaluation of Proanthocyanidins/Chitosan/Lecithin Microspheres as Sustained Drug Delivery System.

Proanthocyanidin (PC) has attracted wide attention on cosmetics and pharmaceutical due to its antioxidant, anticancer, antimicrobial, antiangiogenic, and anti-inflammatory activities. However, PC applications are limited because of its sensitivity to thermal treatment, light, and oxidation and the poor absorption in the gastrointestinal tract. Thus, a novel dosage form of PC needs to be designed to improve its stability and bioavailability for drug delivery. The objective of this study is to fabricate proanthocyanidins/chitosan/lecithin (PC/CTS/LEC) microspheres and investigate various characteristics. In the current study, PC/CTS/LEC microspheres were prepared by spray-drying technology. The yield (61.68%), encapsulation efficiency (68.19%), and drug loading capacity (17.05%) were found in the results. The scanning electron microscope demonstrated that the microspheres were spherical in shape with wrinkled surfaces. DSC study displayed that the microspheres stability was greatly improved when comparing with bare PC. The in vitro release study showed that the 76.92% of PC was released from microspheres within 48 h. The moisture contents of microspheres ranged from 8% to 13%. The swelling rate and tapped density of microspheres were elevated with increasing the concentration of chitosan in the formulations. The moisture uptake of microspheres was saturated at 40°C/RH75% within 12 h. Our results indicated that the stability of PC/CTS/LEC microspheres was enhanced, and it is a promising carrier for sustained drug delivery system.

Berberine Hydrochloride-Loaded Chitosan Nanoparticles Effectively Targets and Suppresses Human Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a common epithelial malignancy that occurs in the nasopharynx and it is one of the high incidences of malignant tumors in China. As previous reports, berberine hydrochloride (BH) possesses a repressive effect on the proliferation of various cancer types. But the application of BH was hampered for a long time due to its hydrophobic properties, along with poor stability and bioavailability. In this study, folate acid modified chitosan nanoparticles loaded berberine hydrochloride (BH/FA-CTS NPs) were prepared by the ionic cross-linking technique, the physicochemical properties and the influence of BH/FA-CTS NPs on proliferation, migration and apoptosis in human nasopharyngeal carcinoma CNE-1 cells were studied in vitro and in vivo. Results of scanning electron microscopy (SEM) images showed that BH/FA-CTS NPs were sphere and the diameter was 258.2±9.1 nm. The drug loading and encapsulation efficiency were 8.17±1.12% and 87.73±4.21%, respectively. The drug release kinetics exhibited a slower and sustained release over a period of 48 h. Moreover, results of MTT assay and scratch assay displayed that BH/FA-CTS NPs inhibited proliferation and migration of CNE-1 cells remarkably. BH/FA-CTS NPs promoted apoptosis and necrosis of CNE-1 cells. And BH/FA-CTS NPs displayed distinguished higher tumor inhibition than control group, free BH and BH/CTS NPs in vivo. Therefore, as a nanocomposite, BH/FA-CTS NPs provide a new method and option for the treatment of nasopharyngeal carcinoma patients.

Cyclosporine A/porous quaternized chitosan microspheres as a novel pulmonary drug delivery system.

N-[(2-Hydroxyl)-propyl-3-trimethyl ammonium] chitosan chloride (HTCC), a hydrosoluble chitosan derivative, has been extensively investigated as a class of drug delivery vehicles because of its unique features. However the studies on HTCC for pulmonary delivery systems have been rarely conducted. This study aimed to design porous microspheres (MS) containing cyclosporine A (CsA) using HTCC as the carrier. The physicochemical properties and biocompatibility of the MS were evaluated. The in vivo efficacy of MS was evaluated in an asthmatic rat model after pulmonary administration. The results showed that porous MS suitable for inhalation could be readily produced by spray drying method. Optimized porous MS in this study exhibited to be biocompatible and safe to use in the lung, and they were effective in suppression of inflammation in the asthmatic rat model. Above all, our results suggested that HTCC porous MS are promising drug carriers for pulmonary drug delivery.