摘要
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[Cu^(Ⅰ)Cu^(Ⅱ)Cl_(2)(VBio)]·CH_(3)OH(VBio=deprotonated O-vanillin biotinylhydrazone),denoted VBio-CuⅠCuⅡ,was rationally designed and synthesized successfully.This targeted Fenton-like agent,VBio-Cu^(Ⅰ)Cu^(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.Owing to the obvious cell selectivity discrepancy of biotin towards normal and cancerous cells,VBio-Cu^(Ⅰ)Cu^(Ⅱ) was able to preferentially accumulate in tumor cells.Meanwhile,the Cu^(Ⅰ) metal center could be used as a Fenton-like agent to generate ^(·)OH.Furthermore,the Cu^(Ⅱ) in VBio-Cu^(Ⅰ)Cu^(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.More importantly,in vivo results further demonstrate that VBio-Cu^(Ⅰ)Cu^(Ⅱ) 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.
基金
supported by the National Natural Science Foundation of China(22075056,21861005,21964005,and 22177022)
Natural Science Foundation of Guangxi Province(no.2019GXNSFFA245006)
the Foundation of State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources(CMEMR2018-C15).
