Phorbiplatin, a Highly Potent Pt(IV) Antitumor Prodrug That Can Be Controllably Activated by Red Light

Summary Selective activation of prodrugs within a tumor is particularly attractive because of their low damage to normal tissue. Here, we report the design, photoactivation mechanism, and antitumor activity of a red-light-activatable Pt(IV) prodrug based on oxaliplatin, a first-line clinical antineoplastic. This small-molecule prodrug, designated as phorbiplatin, has controllable activation property: it is shown to be inert in the dark but under short-period irradiation with low intensity of red light (7 mW/cm2), without the need of any external catalyst, phorbiplatin is rapidly reduced to oxaliplatin. The prodrug displays photocytotoxicity that is up to 1,786 times greater than that of oxaliplatin in human carcinoma cells, and it is also significantly active in vivo. The controllable activation property and superior antitumor activity of phorbiplatin may suggest a novel strategy for the design of visible light-activatable platinum prodrugs to reduce the adverse effects and conquer drug resistance of traditional platinum chemotherapy.