Polycarbonate-BasedPolymersome Photosensitizers withCell-Penetrating Properties for Improved Killing of Cancer Cells

Polymer-based photosensitizers have found various applications in photodynamic therapy (PDT). However, the absence of targeting ability commonly results in a substantial reduction in photosensitizer accumulation at the tumor site, significantly limiting the therapeutic efficacy of the system. In addition, the development of biodegradable polymeric photosensitizers is of critical importance for biological applications. In this work, we present the development of guanidine-functionalized biodegradable photosensitizers based on poly(trimethylene carbonate) (PTMC) block copolymers, which can self-assemble into polymersomes. The presence of guanidine groups on the surface of polymersomes can significantly enhance the cellular uptake efficiency of photosensitizers, thereby improving the intracellular production of reactive oxygen species (ROS). The in vitro study demonstrates that the guanidinylated polymersome photosensitizers can promote the killing of cancer cells compared to unfunctionalized polymersomes in the presence of light irradiation. The guanidine-functionalized PTMC-based polymersome photosensitizers, with the integration of cell-targeting ability and biodegradability, are anticipated to provide a novel strategy for developing advanced biomedical polymer systems for PDT.