Super-efficient <i>in Vivo</i> Two-Photon Photodynamic Therapy with a Gold Nanocluster as a Type I Photosensitizer

Abstract

Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic technique that can induce the regression of targeted lesions <i>via</i> generating 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 <i>in vivo</i> PDT 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 ∼ 10⁶ GM), efficient ROS generation, a type I photochemical mechanism, and negligible <i>in vivo</i> toxicity. With AuNC@DHLA as the photosensitizer, highly efficient <i>in vivo</i> TP-PDT has been achieved.