Super-efficient in VivoTwo-Photon Photodynamic Therapy with a Gold Nanocluster as a Type I Photosensitizer

Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic technique that can induce the regression of targeted lesions viagenerating excess cytotoxic reactive oxygen species. However, due to the limited penetration depth of visible excitation light and the intrinsic hypoxia microenvironment of solid tumors, the efficacy of PDT in the treatment of cancer, especially deep-seated or large tumors, is unsatisfactory. Herein, we developed an efficient in vivoPDT system based on a nanomaterial, dihydrolipoic acid coated gold nanocluster (AuNC@DHLA), that combined the advantages of large penetration depth in tissue, extremely high two-photon (TP) absorption cross section (σ2∼ 106GM), efficient ROS generation, a type I photochemical mechanism, and negligible in vivotoxicity. With AuNC@DHLA as the photosensitizer, highly efficient in vivoTP-PDT has been achieved.