Precise photodynamic therapy: Penetrating the nuclear envelope with photosensitive carbon dots

Abstract

Photodynamic therapy (PDT) has drawn significant attention as a noninvasive cancer treatment. At present, PDT applications are limited in vivo because of the short lifetime and limited diffusion distance of cytotoxic reactive oxygen species (ROS) in the cellular environment. We propose to overcome this challenge by generating limited and short-lived ROS that are localized in key organelles, particularly the nucleus, in tumor cells. We developed Se/N-doped carbon dots (Se/N-CDs) as a photosensitizer for PDT. The Se/N-CDs were shown to bind RNA selectively by digestion experiments, isothermal titration microcalorimetry, and cell dyeing with RNA probes. Se/N-CDs near the nuclear membrane produced ROS that damaged the membrane under light irradiation, permitting the entry of more Se/N-CDs and thereby improving the conversion efficiency of photosensitization. Furthermore, in vitro and in vivo experiments indicated that the Se/N-CDs could inhibit tumor growth more effectively by PDT within the nucleus.