Self‐Sacrificially Degradable Pseudo‐Semiconducting Polymer Nanoparticles that Integrate NIR‐II Fluorescence Bioimaging, Photodynamic Immunotherapy, and Photo‐Activated Chemotherapy

Abstract

Semiconducting polymers (SP) hold great promise for cancer phototherapy due to their excellent optical properties; however, their clinical application is still hampered by their poor biodegradability. Herein, a self-sacrificially biodegradable pseudo-semiconducting polymer (PSP) for NIR-II fluorescence bioimaging, photodynamic immunotherapy, and photoactivated chemotherapy (PACT) is reported. The PSP can further co-assemble with an amphiphilic polyester with pendant doxorubicin (DOX) in its side chains via reactive oxygen species (ROS)-responsive thioketal linkages (PE^DOX ), which are denoted as NP@PE^DOX /PSP. The NP@PE^DOX /PSP can accumulate at tumor sites and generate ROS for photodynamic immunotherapy as well as near-infrared-II fluorescence (NIR-II) for bioimaging upon irradition at 808 nm. The ROS could break up thioketal linkages in PE^DOX , resulting in rapid doxorubicin (DOX) release for PACT. Finally, both PE^DOX and PSP are degraded sacrificially by intracellular glutathione (GSH), resulting in the dissociation of NP@PE^DOX /PSP. This work highlights the application of self-sacrificially degradable PSP for NIR-II fluorescence bioimaging, photodynamic immunotherapy, and PACT in cancer therapy.