1. Hyaluronic acid-decorated redox-sensitive chitosan micelles for tumor-specific intracellular delivery of gambogic acid.
- Author
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Xu W, Wang H, Dong L, Zhang P, Mu Y, Cui X, Zhou J, Huo M, and Yin T
- Subjects
- A549 Cells, Animals, Antineoplastic Agents pharmacology, Apoptosis, Calorimetry, Differential Scanning, Cell Proliferation drug effects, Cell Survival drug effects, Chitosan chemical synthesis, Humans, Hyaluronic Acid chemical synthesis, Mice, Inbred BALB C, Mice, Nude, Nanoparticles chemistry, Neoplasms pathology, Oxidation-Reduction, Propionates chemical synthesis, Propionates chemistry, Proton Magnetic Resonance Spectroscopy, Reproducibility of Results, Tissue Distribution drug effects, Tumor Burden drug effects, Xanthones pharmacology, Chitosan chemistry, Drug Delivery Systems methods, Hyaluronic Acid chemistry, Micelles, Neoplasms drug therapy, Xanthones administration & dosage, Xanthones therapeutic use
- Abstract
Introduction: Herein, a hyaluronic acid (HA)-coated redox-sensitive chitosan-based nanoparticle, HA(HECS-ss-OA)/GA, was successfully developed for tumor-specific intracellular rapid delivery of gambogic acid (GA). Materials and methods: The redox-sensitive polymer, HECS-ss-OA, was prepared through a well-controlled synthesis procedure with a satisfactory reproducibility and stable resulted surface properties of the assembled cationic micelles. GA was solubilized into the inner core of HECS-ss-OA micelles, while HA was employed to coat outside HECS-ss-OA/GA for CD44-mediated active targeting along with protection from cation-associated in vivo defects. The desirable redox-sensitivity of HA(HECS-ss-OA)/GA was demonstrated by morphology and particle size changes alongside in vitro drug release of nanoparticles in different simulated reducing environments. Results: The results of flow cytometry and confocal microscopy confirmed the HA-receptor mediated cellular uptake and burst drug release in highly reducing cytosol of HA(HECS-ss-OA)/GA. Consequently, HA(HECS-ss-OA)/GA showed the highest apoptosis induction and cytotoxicity over the non-sensitive (HA(HECS-cc-OA)/GA) and HA un-coated (HECS-ss-OA/GA) controls against A549 NSCLC model both in vitro and in vivo. Furthermore, a diminished systemic cytotoxicity was observed in HA(HECS-ss-OA)/GA treated mice compared with those treated by HA un-coated cationic ones and GA solution., Competing Interests: The authors report no conflicts of interest in this work.
- Published
- 2019
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