In situ injectable thermoresponsive nanocomposite hydrogel based on hydroxypropyl chitosan for precise synergistic calcium-overload, photodynamic and photothermal tumor therapy

Abstract

Traditional therapies have poor accuracy and significant toxic side effects in the process of tumor treatment. The non-traditional treatment methods with high accuracy and efficacy are worth exploring and investigating. Herein, a strategy that enables precise and synergistic therapies of calcium-overload, photodynamic, and photothermal through facile near infrared (NIR) irradiation was carried out base on the injectable and self-healable hydrogel encapsulating indocyanine green (ICG)-loaded and bovine serum albumin (BSA)-modified calcium peroxide (CaO2) nanoparticles (ICG@CaO2-BSA NPs) and bismuth sulfide (Bi2S3) nanorods. The hydrogel fabricated through the dynamic Schiff-base bonds between hydroxypropyl chitosan (HPCS) and aldehyde-modified Pluronic F127 (F127-CHO) as the delivery substrate for functional substances could adhere and grip tumor tissues due to the adhesion of hydroxyl groups in HPCS and the hydrophobic aggregation caused by thermoresponsiveness of F127-CHO. CaO2 in ICG@CaO2-BSA NPs decomposed in the tumor micro-acidic environment to produce calcium ions (Ca2+) and hydrogen peroxide (H2O2), while ICG generated reactive oxygen species (ROS) under NIR irradiation, the photothermal effect of Bi2S3 nanorods and ICG under NIR irradiation could increase the temperature of tumor tissues and ultimately achieve precise tumor cell destruction. Therefore, this strategy will provide promising prospects for precise and efficient treatment of tumors.