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 highly spatiotemporally precise cancer therapy. Photosensitizers (PSs) with high singlet oxygen ( ¹ O ₂ ) generation efficiency and large two-photon absorption (2PA) cross-sections are highly desirable, but the availability of such PSs is limited by challenges in molecular design. In this work, we report that the polymerization of small-molecule PSs with aggregation-induced emission (AIE) could yield conjugated polymer PSs with good brightness, high ¹ O ₂ generation efficiency, and large 2PA cross-sections. A pair of 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.