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

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 O₂ ). 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.