Facile synthesis of multi-stimuli responsive biocompatible trimethyl chitosan-based nanogel as potential nanocarrier for photothermal chemotherapy

Development of multi-stimuli responsive nanocarriers for cancer treatment with combined or synergistic functionalities is highly attractive and challenging for overcoming the limitations related to single-stimuli responsive ones. Herein, we report the synthesis of multi-stimuli responsive biocompatible nanogel comprising crosslinked poly(2-hydroxyethyl methacrylate) core and trimethyl chitosan (TMC) periphery by a facile visible light-initiated surfactant-free emulsion polymerization, and its use as multi-stimuli responsive nanocarrier. Some of polymerization parameters, such as TMC type and crosslinker concentration were optimized, which were found to strongly affect the nanogel's thermoresponsiveness. At the optimal condition, using TMC (45% degree of quaternization) and 5% MBA crosslinker, the synthesized nanogel exhibited areversible upper critical solution temperature (UCST)-type volume phase transition above 30 degrees C in acidic aqueous environment (pH 4.5-5). Moreover, the incorporation of sodium copper chlorophyllin as a bio-based photosensitive agent and honokiol model drug to such nanogel not only introduced the hyperthermic effect under light irradiation, but also triggered the release of encapsulated honokiol. The co-loaded nanogel, possessing combined photothermal and chemotherapeutic effect, enhanced the antitumor efficacy against Calu-3 cells. These results showed that the nanogel with pH- and light-dependent UCST-type thermoresponsiveness can be synthesized through the facile method and is promising for being used as multifunctional nanocarrier in cancer therapy.