Polyoxalate with aggregation-induced emission feature as a self-immolative polymeric photosensitizer for efficient photodynamic therapy

Photodynamic therapy (PDT) is a promising cancer treatment due to its precision, minimal invasiveness, and low drug resistance. Nonetheless, currently developed photosensitizers (PSs) could not fully fulfill the requirements for safe and efficient PDT owing to the following issues, including widespread biodistribution, unsatisfactory biodegradability, poor colloidal stability and photostability. To address some of these issues, we reported the fabrication of a self-immolative polymeric PS for the first time by conjugation of an aggregation-induced emission (AIE)-active PS (named TPACN) and polyethylene glycol (PEG) using oxalyl chloride as the bridge. The resultant polyoxalate (designated TPACN@PEG) can self-assemble into water dispersible nanoparticles with suitable size (about 130 nm), endowing its passive tumor targeting potential via enhanced permeability retention effect. TPACN@PEG can be degraded into small molecules by reaction with H2O2. Owing to the typical donor- acceptor structure and AIE feature of TPACN, TPACN@PEG displays intensive fluorescence, high reactive oxygen species (ROS) generation capability, and considerable photodynamic effects towards cancer cells. We believe this work will provide some new insights for development of highly efficient and safe PDT and PDT-based combination therapies.