Polymerization-Enhanced Two-Photon Photosensitization for Precise Photodynamic Therapy.

Two-photon excited photodynamic therapy (2PE-PDT) has attracted great attention in recent years due to its great potential for deep tissue and high spatiotemporal precise cancer therapy. Photosensitizers (PSs) with high singlet oxygen (1O2) generation efficiency and large two-photon absorption (2PA) cross section are highly desirable, but the availability of such PSs is limited by challenges in molecular design. In this work, we report that polymerization of small molecule PSs with aggregation-induced emission (AIE) could yield conjugated polymer PSs with good brightness, high 1O2 generation efficiency and large 2PA cross section. Two conjugated polymer PSs were designed and synthesized and the corresponding AIE PS dots were prepared by nanoprecipitation, which exhibited outstanding 2PE-PDT performance in in vitro cancer cell ablation and in vivo zebrafish liver tumor treatment. Our work highlights a strategy to design highly efficient PSs for 2PE-PDT.