Cascade Enzymatic Semiconducting Polymer Nanocomposites for NIR-II Light-Mediated Photothermal-Chemodynamic Combinatorial Therapy

Abstract

Chemodynamic therapy (CDT) has been widely adopted for cancer therapy, but its efficacy is limited by some factors such as low intratumoral H2O2 level and glutathione (GSH) scavenging in tumor microenvironment (TME). NIR-II photothermal therapy (PTT) enhances catalytic kinetics and alleviates TME restrictions via deep tissue penetration and spatiotemporally controlled hyperthermia. Herein, we report a tumor-targeted nanocomposite called SPMG by integrating bovine serum albumin (BSA)-MnO2, a semiconducting polymer (SPII), and glucose oxidase (GOx) to enable NIR-II-triggered PTT and enzyme-augmented CDT. The semiconducting polymer SPII shows high NIR-II photothermal conversion efficiency (λ = 1064 nm) to enable precision PTT through tumor-localized hyperthermia. It drives self-assembly with BSA-MnO2 via nano-coprecipitation to form SPM, which serves as stable carrier for GOx immobilization. The resultant nanocomposites (SPMG) synergize the dual therapeutic modalities in addition to NIR-II PTT: MnO2 releases Mn2+ ions for CDT via Mn2+-catalyzed Fenton-like reaction and GOx-mediated glucose oxidation to generate endogenous H2O2. This cascade fuels Mn2+-catalyzed reaction, thus achieving self-enhanced CDT through •OH burst, with concurrent mild hyperthermia (≤ 45 °C) for amplifying enzymatic activity and tumor-specific ROS accumulation. This NIR-II light-mediated PTT-CDT combinatorial therapy enables effective treatments of subcutaneous 4T1 tumors in mouse models.