A Multi-Sensitive Chitosan Nanomicelles for Targeted Anticancer Drug Delivery

In this study, different molecular weights and degrees of acetylation of chitosan are prepared from microwave deacetylation and sodium nitrite depolymerization using reactions. Core-shell structured nanomicelles (CS-SS-PL F127 NMs) are prepared by interface cross-linking of CS and pluronic F127 with disulfide bonds. The temperature, pH and bio-redox responsive properties of the nanomicelles and their effects on drug loading ad release are investigated. In the second year, chitosan and arginine are linked together by forming covalent bonds to obtain chitosan-arginine (CS-Arg) conjugate for the preparation of CS-Arg-SS-PL F127 NMs. The CS-Arg-SS-PL F127 NMs are decorated with hyaluronic acid via formation of a stable electrostatic attraction between CS-Arg and hyaluronic acid. MCF-7 and multi-drug resistant breast cancer cell (MCF-7/ADR) are cultured with the nanomicelles to investigate the specific binding interaction between the nanomicelles and CD44, and cellular uptake of the nanomicelles. In the third year, we further study the combination of photochemical and chemotherapeutic effects to overcome multi-drug resistance of the cancer cells. The ultraviolet light-induced pH-jump and DOX release, and the near-infrared photothermal effects of the photosensitizer-loaded CS-Arg-SS-PL F127 NMs are investigated. Cytotoxicity of MCF-7/ADR cells caused by the combined light-induced pH jump, photothermal and chemotherapy effects are also examined.