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

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.