Combination prostate cancer therapy via CuTCPP-MOF-mediated chemodynamic and photodynamic effects

Abstract

Prostate cancer remains one of the most common malignant tumors among men worldwide, and treatment options are limited in the advanced stage. To address this challenge, we have developed a pH-responsive copper porphyrin metal–organic framework (CuTCPP-MOF), which integrates photodynamic therapy (PDT) and chemodynamic therapy (CDT). It enables efficient electron transfer and ROS generation. Under 488 nm laser irradiation, MOF acts as a self-sensitizing photosensitizer to generate single-state oxygen (¹O₂), which gradually releases Cu²⁺ in an acidic environment. Subsequently, it is reduced to Cu⁺ by intracellular glutathione (GSH), achieving continuous consumption of GSH and enhancing the Fenton-like reaction to promote the continuous formation of hydroxyl radicals (˙OH). This amplifies the oxidative stress within tumor cells. In vitro experiments have shown that ROS accumulation and mitochondrial membrane depolarization lead to apoptosis of RM-1 prostate cancer cells. In vivo, CuTCPP-MOF combined with laser irradiation can significantly inhibit tumor growth without causing systemic toxicity and hemolysis. Histological analysis confirmed that after treatment, the apoptosis of tumor cells was enhanced and their proliferation ability was reduced. In conclusion, CuTCPP-MOF is a promising nano-therapeutic agent that can work in synergy with PDT and CDT to achieve effective and safe treatment of prostate cancer.