More importantly, in vivo results further demonstrate that VBio-Cu ICu II could significantly inhibit tumor growth without obvious damage toward major organs. Furthermore, the Cu II in VBio-Cu ICu II was available for successive ˙OH production via a Cu I/Cu II-circulation strategy under a GSH-rich tumor site, thereby improving catalytic efficiency. Meanwhile, the Cu I metal center could be used as a Fenton-like agent to generate ˙OH. Owing to the obvious cell selectivity discrepancy of biotin towards normal and cancerous cells, VBio-Cu ICu II was able to preferentially accumulate in tumor cells. This targeted Fenton-like agent, VBio-Cu ICu II, is constructed from a hydroxyl radical-producible Cu I ion, a Cu II center as a GSH depletor for an augmented CDT effect, and a biotin moiety as a cancer-targeting unit. Compared to traditional CDT nanomaterials, herein, an atomically-precise biotinylated Cu( I/ II) complex ♼H 3OH (VBio = deprotonated O-vanillin biotinylhydrazone), denoted VBio-Cu ICu II, was rationally designed and synthesized successfully. 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.
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