Comparative study of the direct and photocatalytic light activation of platinum(IV) prodrugs

Here, we present a comparative study of direct and photocatalyst-mediated photoactivation of reporter-functionalised Pt(IV) prodrugs, Carbo-4NP and CarboNap. Direct blue-light irradiation and green-light activation using the photocatalyst Rose Bengal both achieved rapid and complete Pt(IV) reduction in solution, monitored by UV-Vis and fluorescence spectroscopy. Translation to live cells revealed a marked divergence between the two approaches. Direct blue light (415 nm) photoactivation produced >300-fold enhancement in fluorescence intensities upon probe activation and >10-fold in cytotoxicity. Photocatalytic activation was considerably less effective in cells despite its excellent solution-phase performance. These findings identify direct photoactivation as the superior strategy for intracellular activation of Pt(IV) prodrugs and support the further development of direct light-activated platinum therapeutics.