A dual-targeted small-molecule photosensitizer with enhanced dual antitumor and anti-vascular effect for metastatic advanced prostate cancer photodynamic therapy

Advanced prostate cancer is regarded as a fatal disease, characterized by limited treatment options, poor prognosis and considerable tumor metastasis closely related to angiogenesis. Photodynamic therapy emerges as a promising and safe therapeutic modality for advanced prostate cancer with high metastasis and high fatality rate due to its focal damage to tumor cells, as well as its anti-angiogenesis and antitumor immunity capabilities. Herein, a tumor-targeting vascular disrupting agent ASA-404 was introduced to conjugate with a photosensitizer ZnPc for targeted prostate cancer treatment and enhanced vascular-disrupting efficiency. Notably, this novel organic small-molecule photosensitizer Pc-ASA possess a well-defined chemical structure and purity, as well as good photophysical and photochemical properties, which are of benefit for clinical approval and application. Pc-ASA prefers to accumulate in both prostate cancer cells and vascular endothelial cells. Moreover, the conjugation of ASA-404 boosts the photodynamic anticancer effect of Pc-ASA towards both prostate cancer cells and vascular endothelial cells. Ultimately, PC-ASA can successfully inhibit the migration and metastasis of prostate cancer cells, offering significant advantages in advanced prostate cancer management. Our study might open a window in the development of the tumor and vascular dual-targeted small-molecule photosensitizers, with the potential to achieve safe and efficient treatment of metastatic advanced prostate cancer through dual mode of antitumor and anti-vascular action.