Cascade-Enhanced Pt Nanozyme Platform Anchored on Microgels for Effective Lactate Depletion and EndoMT Attenuation Post-Myocardial Infarction

Myocardial infarction (MI) often leads to excessive lactate accumulation, which drives endothelial-to-mesenchymal transition (EndoMT) and subsequent myocardial fibrosis, because the hypoxic environment characteristic of MI diminishes the catalytic efficiency of lactate oxidase (LOx). In this study, platinum (Pt) nanozymes with catalase-like (CAT-like) activity were introduced in this study, which catalyzed the decomposition of hydrogen peroxide (H 2 O 2 ) to generate oxygen (O 2 ), thereby enhancing LOx activity. A strategy involving microgel-anchored LOx-loaded Pt nanozymes (PPtL@MGs) was proposed by loading LOx-loaded Pt nanozymes to microgels, enabling targeted delivery and prolonged retention within the infarcted myocardium. The PPtL@MGs exhibited robust CAT-like activity and effectively enhanced LOx-mediated lactate clearance in vitro , thereby alleviating hypoxia/H 2 O 2 -induced EndoMT in HUVECs. Consequently, it promoted vascular endothelial cadherin (VE-cadherin) expression, suppressed fibroblast-specific protein 1 (FSP1), reduced myocardial fibrosis, and significantly improved cardiac function in vivo . These results demonstrate the potential of this microgel-anchored nanozyme system, which enables cascade-enhanced lactate modulation through O 2 generation and effective lactate clearance, for the effective treatment of MI-induced fibrosis and dysfunction.