A Vanadium(II) Photosensitizer Delivered by Human Serum Albumin for Photodynamic Therapy.

Photodynamic therapy (PDT) is an established clinically approved treatment; however, the development of next-generation photosensitizers remains constrained by the reliance on scarce precious-metal scaffolds and poor pharmacological properties. Earth-abundant first-row transition metals offer an attractive alternative, but their application in PDT remains underexplored. Herein, we report the first vanadium(II) photosensitizer for PDT and show that its biological activity can be unlocked through loading into human serum albumin (HSA), a strategy intended to improve its pharmacological properties. The resulting HSA-bound complex showed negligible dark toxicity and induced pronounced light-dependent cytotoxicity upon blue- and red-light irradiation in human colon carcinoma cells. Mechanistic studies revealed that the HSA-bound complex preferentially accumulates in lysosomes, where red-light irradiation triggers singlet oxygen generation and promotes apoptosis. This work establishes vanadium(II) complexes as a new class of photosensitizers for photodynamic therapy and opens new opportunities for the design of first-row transition-metal photosensitizers with improved photophysical properties.