Copper(II)–Graphitic Carbon Nitride Triggered Synergy: Improved ROS Generation and Reduced Glutathione Levels for Enhanced Photodynamic Therapy

TLDR

Graphitic carbon nitride is a photosensitizer for ROS generation in photodynamic therapy, but cancer cells’ overexpression of glutathione limits its therapeutic effectiveness. Redox‑active Cu⁺–g‑C₃N₄ catalyzes oxygen reduction to superoxide or hydrogen peroxide to hydroxyl radicals, boosting ROS generation. Integration of Cu²⁺ with g‑C₃N₄ nanosheets markedly increases light‑triggered ROS production while depleting intracellular GSH, thereby enhancing photodynamic therapy efficacy.

Abstract

Abstract Graphitic carbon nitride (g‐C 3 N 4 ) has been used as photosensitizer to generate reactive oxygen species (ROS) for photodynamic therapy (PDT). However, its therapeutic efficiency was far from satisfactory. One of the major obstacles was the overexpression of glutathione (GSH) in cancer cells, which could diminish the amount of generated ROS before their arrival at the target site. Herein, we report that the integration of Cu 2+ and g‐C 3 N 4 nanosheets (Cu 2+ –g‐C 3 N 4 ) led to enhanced light‐triggered ROS generation as well as the depletion of intracellular GSH levels. Consequently, the ROS generated under light irradiation could be consumed less by reduced GSH, and efficiency was improved. Importantly, redox‐active species Cu + –g‐C 3 N 4 could catalyze the reduction of molecular oxygen to the superoxide anion or hydrogen peroxide to the hydroxyl radical, both of which facilitated the generation of ROS. This synergy of improved ROS generation and GSH depletion could enhance the efficiency of PDT for cancer therapy.