pH/Temperature Dual-Sensitive Hydrogel Based on Carboxymethyl Chitosan and a Pluronic for Combined Chemo-Photothermal Therapy
Jinping Song, Yiming Zhang, Xuefeng Yang, Yangyang Li, Xin Wang, Rupei Tang
Abstract
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.