A Smart Photosensitizer–Manganese Dioxide Nanosystem for Enhanced Photodynamic Therapy by Reducing Glutathione Levels in Cancer Cells

TLDR

Photodynamic therapy kills cancer cells by generating reactive oxygen species, but the high glutathione levels in tumors neutralize these species. This study develops a photosensitizer–MnO₂ nanosystem to overcome glutathione‑mediated resistance and achieve highly efficient photodynamic therapy. The nanosystem consists of MnO₂ nanosheets that adsorb chlorin e6, protect it from photobleaching, deliver it into cells, and are reduced by intracellular glutathione, causing disintegration that releases chlorin e6 and depletes glutathione. The system suppresses extracellular singlet‑oxygen production, enhances tumor cell killing, and provides a fluorescence signal upon MnO₂ dissolution for real‑time monitoring of delivery efficacy.

Abstract

Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species to kill cancer cells. However, a high concentration of glutathione (GSH) is present in cancer cells and can consume reactive oxygen species. To address this problem, we report the development of a photosensitizer-MnO2 nanosystem for highly efficient PDT. In our design, MnO2 nanosheets adsorb photosensitizer chlorin e6 (Ce6), protect it from self-destruction upon light irradiation, and efficiently deliver it into cells. The nanosystem also inhibits extracellular singlet oxygen generation by Ce6, leading to fewer side effects. Once endocytosed, the MnO2 nanosheets are reduced by intracellular GSH. As a result, the nanosystem is disintegrated, simultaneously releasing Ce6 and decreasing the level of GSH for highly efficient PDT. Moreover, fluorescence recovery, accompanied by the dissolution of MnO2 nanosheets, can provide a fluorescence signal for monitoring the efficacy of delivery.