A Synergistic Strategy Combining Chemotherapy and Photodynamic Therapy to Eradicate Prostate Cancer

Prostate cancer is the most prevalent cancer among men in the United States and is a leading cause of cancer-related death. Prostate specific membrane antigen (PSMA) has been established as a biomarker for prostate cancer diagnosis and treatment. This study aimed to develop a novel theranostic agent, PSMA-1-MMAE-Pc413, which integrates a PSMA-targeting ligand, the photosensitizer Pc413, and the microtubular inhibitor monomethyl auristatin E (MMAE) for synergistic therapeutic efficacy. In vitro uptake studies revealed that PSMA-1-MMAE-Pc413 demonstrated selective and specific uptake in PSMA-positive PC3pip cells but not in PSMA-negative PC3flu cells, with the uptake in PC3pip cells being approximately three times higher. In vitro cytotoxicity assays showed that, when exposed to light, PSMA-1-MMAE-Pc413 had a synergistic effect, leading to significantly greater cytotoxicity in PSMA-positive cells (IC