Metal ion interference therapy(MIIT)employs biocatalytic interference mechanisms,such as Fenton-like reactions and oxidative stress amplification,to disrupt tumor redox homeostasis.Notably,this approach demonstrates e...Metal ion interference therapy(MIIT)employs biocatalytic interference mechanisms,such as Fenton-like reactions and oxidative stress amplification,to disrupt tumor redox homeostasis.Notably,this approach demonstrates excellent therapeutic efficacy and safety.However,biocatalytic efficiency is often hampered by the strong antioxidant system of tumor cells and the catalytic efficiency of metal ions.To address this limitation,in this study,we engineered copper-zinc bimetallic sulfide nanoparticles(CZS NPs)to implement a dual-action therapeutic strategy.The Zn^(2+)within CZS NPs exploit the enzymatic activity of nicotinamide adenine dinucleotide phosphate(NADPH)oxidase(NOX)to amplify tumor oxidative stress,while Cu^(+)boosts Fenton-like catalytic activity,intensifying oxidative stress damage.These components synergistically drive the NOX/superoxide dismutase(SOD)/peroxidase(POD)nanocascade reaction,achieving the combinatorial activation of three cell death pathways:ferroptosis,cuproptosis,and apoptosis.The synthesized CZS NPs achieve remarkable therapeutic efficacy in tumor cells through a fully optimized MIIT.These findings suggest a potential strategy for MIIT-mediated biocatalytic tumor therapy.展开更多
基金financially supported by the Natural Science Foundation of Zhejiang Province(No.LR22E010001)the National Natural Science Foundation of China(No.52073258)+1 种基金the Fundamental Research Funds for the Provincial Universities of Zhejiang(No.RF-B2022006)the R&D Program of Zhejiang University of Technology(No.KYY-HX-20190730)
文摘Metal ion interference therapy(MIIT)employs biocatalytic interference mechanisms,such as Fenton-like reactions and oxidative stress amplification,to disrupt tumor redox homeostasis.Notably,this approach demonstrates excellent therapeutic efficacy and safety.However,biocatalytic efficiency is often hampered by the strong antioxidant system of tumor cells and the catalytic efficiency of metal ions.To address this limitation,in this study,we engineered copper-zinc bimetallic sulfide nanoparticles(CZS NPs)to implement a dual-action therapeutic strategy.The Zn^(2+)within CZS NPs exploit the enzymatic activity of nicotinamide adenine dinucleotide phosphate(NADPH)oxidase(NOX)to amplify tumor oxidative stress,while Cu^(+)boosts Fenton-like catalytic activity,intensifying oxidative stress damage.These components synergistically drive the NOX/superoxide dismutase(SOD)/peroxidase(POD)nanocascade reaction,achieving the combinatorial activation of three cell death pathways:ferroptosis,cuproptosis,and apoptosis.The synthesized CZS NPs achieve remarkable therapeutic efficacy in tumor cells through a fully optimized MIIT.These findings suggest a potential strategy for MIIT-mediated biocatalytic tumor therapy.
