Near-infrared light-activated ROS generation using semiconducting polymer nanocatalysts for photodynamic–chemodynamic therapy

Chemodynamic therapy (CDT) is an emerging treatment strategy for cancer, but the low therapeutic efficacy and potential side effects still limit its applications. In this study, we report a semiconducting polymer nanocatalyst (PGFe) that can generate reactive oxygen species (ROS) only upon near-infrared (NIR) light-activation for photodynamic therapy (PDT)-synergized CDT. Such PGFe consists of a semiconducting polymer as a photosensitizer, iron oxide (Fe3O4) nanoparticles as CDT agents, and glucose oxidase (GOx), all of which are loaded into a singlet oxygen (1O2)-responsive nanocarrier. Under NIR laser irradiation, PGFe produces 1O2 through a photosensitizer-mediated PDT effect, and the produced 1O2 destroys the 1O2-responsive nanocarriers, leading to controlled releases of Fe3O4 nanoparticles and GOx. In a tumor microenvironment, GOx catalyzes glucose degradation to form hydrogen peroxide (H2O2), and thus the CDT effect of Fe3O4 nanoparticles is greatly improved. As such, an amplified ROS level in tumor cells is obtained by PGFe to induce cell death. PGFe can be utilized to treat subcutaneous 4T1 tumors, observably inhibiting the tumor growth and suppressing lung and liver metastasis. This study thus provides a NIR light-activated ROS generation strategy for precise and effective treatments of tumors.