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

Adv Mater. 2022 Jul;34(29):e2203236. doi: 10.1002/adma.202203236. Epub 2022 Jun 7.

Abstract

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.

Keywords: cytochrome c; ferroptosis; nanozyme; prodrug therapy; starvation.

MeSH terms

  • Animals
  • Catalysis
  • Electron Transport Complex IV
  • Ferroptosis*
  • Mice
  • Nanostructures*
  • Neoplasms*
  • Prodrugs* / pharmacology
  • Prodrugs* / therapeutic use

Substances

  • Prodrugs
  • Electron Transport Complex IV