Dual-Level Reactive Oxygen Species Amplifier for Enhanced Photothermal–Chemodynamic Therapy

Chemodynamic therapy is an appealing modality in cancer treatment. However, its therapeutic effectiveness is impeded by insufficient catalytic efficiency and overexpression of glutathione (GSH) at the tumor site. In this study, a poly­(o-phenylenediamine) (PoPD)@copper sulfide (CuS) nanoplatform was developed as dual-level reactive oxygen species (ROS) amplifier for enhanced photothermal–chemodynamic therapy. The PoPD@CuS nanoplatform exhibited photothermal performance, chemodynamic performance, and GSH-depleting capability. Alongside its improved photothermal conversion efficiency with tumor pH-responsiveness, the photothermal behavior of PoPD@CuS could elevate chemodynamic activity by regulating the temperature spatiotemporally, leading to increased ROS production. Moreover, GSH depletion of PoPD@CuS could suppress ROS scavenging, further enhancing oxidative stress in the tumor region. Consequently, functioning as a dual-level ROS amplifier, PoPD@CuS showcased remarkable effectiveness in photothermal–chemodynamic combination therapy.