A Photoisomerizable Zinc (II) Complex Inhibits Microtubule Polymerization for Photoactive Therapy

Abstract The photoisomerization‐induced cytotoxicity in photopharmacology provides a unique pathway for phototherapy because it is independent of endogenous oxygen. In this study, we developed a biosafe photoisomerizable zinc(II) complex ( Zn1 ), which releases its trans ligand ( trans ‐L1 ) after being irradiated with blue light. This causes the complex to undergo photoisomerization and produce the toxic cis product ( cis ‐L1 ) and generate singlet oxygen ( 1 O 2 ). The resulting series of events caused impressive phototoxicity in hypoxic A431 skin cancer cells, as well as in a tumor model in vivo. Interestingly, Zn1 was able to inhibit tumor microtubule polymerization, while still showing good biocompatibility and biosafety in vivo. This photoisomerizable zinc(II) complex provides a novel strategy for addressing the oxygen‐dependent limitation of traditional photodynamic therapy.