A mixed-valence biotinylated Cu(i/ii) complex for tumor-targeted chemodynamic therapy accompanied by GSH depletion

• Published in: Inorganic chemistry frontiers 2023-07, Vol.10 (14), p.4045-4053
• Main Authors: Hong, Zhaoguo, You, Xin, Zhong, Jingjing, Yao, Di, He-Dong, Bian, Zhao, Shulin, Zhang, Liangliang, Liang, Hong, Fu-Ping, Huang
• Format: Article
• Language: English
• Subjects: Biocompatibility; Biotin; Cancer; Depletion; Hydroxyl radicals; Inorganic chemistry; Nanomaterials; Tumors; Vanillin
• ISSN: 2052-1545; 2052-1553
• DOI: 10.1039/d3qi00254c

Chemodynamic therapy (CDT), in which highly toxic hydroxyl radicals (·OH) could be triggered by a Fenton or Fenton-like reaction to kill cancer cells, has emerged recently. Compared to traditional CDT nanomaterials, herein, an atomically-precise biotinylated Cu(i/ii) complex [CuICuIICl2(VBio)]·CH3OH (VBio = deprotonated O-vanillin biotinylhydrazone), denoted VBio-CuICuII, was rationally designed and synthesized successfully. This targeted Fenton-like agent, VBio-CuICuII, is constructed from a hydroxyl radical-producible CuI ion, a CuII center as a GSH depletor for an augmented CDT effect, and a biotin moiety as a cancer-targeting unit. Owing to the obvious cell selectivity discrepancy of biotin towards normal and cancerous cells, VBio-CuICuII was able to preferentially accumulate in tumor cells. Meanwhile, the CuI metal center could be used as a Fenton-like agent to generate ·OH. Furthermore, the CuII in VBio-CuICuII was available for successive ·OH production via a CuI/CuII-circulation strategy under a GSH-rich tumor site, thereby improving catalytic efficiency. More importantly, in vivo results further demonstrate that VBio-CuICuII could significantly inhibit tumor growth without obvious damage toward major organs. Therefore, this multiple-identity Fenton-like agent could provide an appreciable reference value for the design of atomically precise CDT agents.