Mimicking NADPH oxidase and lipoxygenase by using a biodegradable single-site catalyst <i>via</i> a cascade reaction to trigger tumor-specific ferroptosis.

ABSTRACT: Ferroptosis exhibits promising potential in cancer therapy via lipid peroxidation (LPO) accumulation, while its therapeutic efficacy is normally limited by inadequate ROS production and adverse effects on normal tissues. Here, a TME-activated in situ synthesis of a single-site catalyst (Fe(ii)-PW₁₁) is reported, which triggers ferroptosis by mimicking natural enzyme activities of NADPH oxidase (NOX) and lipoxygenase (LOX) via cascade reactions. Upon degradation of the nanocarrier by the overexpressed GSH in an acidic TME, Fe(ii)-PW₁₁ is obtained through the coordination of Fe²⁺ into lacunary phosphotungstic acid (PW₁₁). Subsequently, Fe(ii)-PW₁₁ catalyzes NADPH depletion and O₂˙^- generation th

SUBMITTER: Ge X 

PROVIDER: S-EPMC12260917 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature