PEGylated Molybdenum-Iodine Nanocluster as a Promising Radiodynamic Agent against Prostatic Adenocarcinoma

The combination of photodynamic therapy and radiotherapy has given rise to a modality called radiodynamic therapy (RDT), based on reactive oxygen species-producing radiosensitizers. The production of singlet oxygen, O₂(¹Δ_g), by octahedral molybdenum (Mo₆) clusters upon X-ray irradiation allows for simplification of the architecture of radiosensitizing systems. In this context, we prepared a radiosensitizing system using copper-free click chemistry between a Mo₆ cluster bearing azido ligands and the homo-bifunctional linker bis-dPEG₁₁-DBCO. The resulting compound formed nanoparticles, which featured production of O₂(¹Δ_g) and efficient cellular uptake, leading to remarkable photo- and radiotoxic effects against the prostatic adenocarcinoma TRAMP-C2 cell line. Spheroids of TRAMP-C2 cells were also used for evaluation of toxicity and phototoxicity. In vivo experiments on a mouse model demonstrated that subcutaneous injection of the nanoparticles is a safe administration mode at a dose of up to 0.08 g kg^-1. The reported results confirm the relevancy of Mo₆-based radiosensitizing nanosystems for RDT.