Smart Dual-Functionalized Gold Nanoclusters for Spatio-Temporally Controlled Delivery of Combined Chemo- and Photodynamic Therapy

We report the preparation of gold nanoclusters (AuNCs) as a delivery vehicle for the clinically approved photodynamic and chemotherapeutic agents Protoporphyrin IX (PpIX) and doxorubicin (DOX), respectively, and their effect on tumor cells. DOX was attached to the gold nanoclusters through a singlet oxygen-cleavable linker and was therefore released after PpIX irradiation with red light, contributing, synergistically with singlet oxygen, to induce cell death. The doubly functionalized AuNCs proved more effective than a combination of individually functionalized AuNCs. Unlike free DOX, the photoactive nanosystem was non-toxic in the absence of light, which paves the way to introduce a spatiotemporal control of the anticancer therapy and could contribute to reducing the undesirable side effects of DOX.