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Several metal-based nanoparticles harboring multivalent elements, such as Cu 2+ /Cu + , Mn 4+/3+ /Mn 2+ , Mo 6+ /Mo 4+ , and Ir 4+ /Ir 3+ , possess strong oxidization, and can directly react with GSH ( via the redox reaction between Cu 2+ and intracellular GSH, and the activation of a Fenton-like reaction by generating Cu + to amplify oxidative stress ( in situ GSH in tumor triggered mCMSNs biodegradation and reduced Cu 2+ into Cu + for enhanced hydroxyl radical production, leading to a powerful inhibition effect on tumors ( 2 , Mn 2 O 3 , and Mn 3 O 4 , possess a similar GSH elimination property to Cu-based nanomaterials, and react with GSH along with the decomposition of MnO x into Mn 2+ for initiation of the Fenton-like reaction ( 2 -based nanoagent with both Fenton metal ion delivery and GSH exhaustion capability (Figure 1E) ( 2+ and GSSG, accompanied by the elimination of intracellular GSH (Figure 1F)