Starvation, Ferroptosis, and Prodrug Therapy Synergistically Enabled by a Cytochrome c Oxidase like Nanozyme

Nanozymes, which are inorganic nanomaterials mimicking natural enzyme activities, are bringing enormous opportunities to theranostics. Herein, a cytochrome c oxidase-like nanozyme (copper-silver alloy nanoparticle, Cu-Ag NP) is demonstrated for nanocatalytic cancer therapy. Loaded with bioreductive predrug (AQ4N), this Cu-Ag nanozyme unprecedentedly enables simultaneous starvation, ferroptosis, and chemical therapy with high specificity, and is able to totally eliminate tumor and greatly prolong the survival rate for 4T1-tumor-bearing mice. The underlying working mechanism is revealed both experimentally and theoretically.

Automated summary

In this study, a nanozyme resembling cytochrome c oxidase was demonstrated for nanocatalytic cancer therapy. By loading a bioreductive predrug, it simultaneously achieved starvation, ferroptosis, and chemical therapy, resulting in significant tumor elimination and increased survival rate in tumor-bearing mice.