pH/Temperature Dual-Sensitive Hydrogel Based on Carboxymethyl Chitosan and a Pluronic for Combined Chemo-Photothermal Therapy

The purpose of this paper is to design an injectable hydrogel containing nanodrugs for combined chemotherapy and photothermal therapy of tumors. Pluronic F127 was oxidized to aldehyde-terminated (AF127) as a precursor of the hydrogel. AF127 reacts with carboxymethyl chitosan to form a dynamic imine bond, thereby obtaining a hydrogel. Sorafenib and ICG were coassembled into a pure nanodrug (S–I NP) capable of combined chemotherapy and photothermal therapy (PTT). By incorporation of S–I NPs into the hydrogel, an injectable pH/temperature dual-responsive nanoparticle-hydrogel composite (S–I NPs@Gel) was obtained. S–I NPs@Gel can form a drug reservoir at the tumor site and gradually release S–I NPs in response to the tumor microenvironment. Sorafenib, a multitargeted antitumor drug, inhibits cell proliferation and induces apoptosis in liver cancer cells. ICG serves as an effective photosensitizer, absorbing near-infrared light to induce strong photothermal effects while generating reactive oxygen species (ROS) that induce cell apoptosis. MTT assay results demonstrate that S–I NPs@Gel exhibits the highest cell toxicity under laser irradiation, reaching 93.3%. Antitumor treatment results reveal that the tumor volume treated by S–I NPs@Gel under irradiation (808 nm, 2 W/cm 2, 5 min) was only 382.9 ± 80.5 mm 3, achieving a tumor growth inhibition rate of 93.5%. Thus, a locally administered system based on pH and temperature-sensitive hydrogels can effectively achieve synergistic antitumor effects.