Issue 14, 2023

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

Abstract

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.

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

Supplementary files

Article information

Article type
Research Article
Submitted
10 фев 2023
Accepted
31 мар 2023
First published
03 апр 2023

Inorg. Chem. Front., 2023,10, 4045-4053

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

Z. Hong, X. You, J. Zhong, D. Yao, H. Bian, S. Zhao, L. Zhang, H. Liang and F. Huang, Inorg. Chem. Front., 2023, 10, 4045 DOI: 10.1039/D3QI00254C

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