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

Abstract

AbstractThe 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 (1O2). 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.