Targeting Ferroptosis by Polydopamine Nanoparticles Protects Heart against Ischemia/Reperfusion Injury

Ferroptosis is a new form of regulated cell death depending on elevated iron (Fe²⁺) and lipid peroxidation levels. Myocardial ischemia/reperfusion (I/R) injury has been shown to be closely associated with Ferroptosis. Therefore, antiferroptosis agents are considered to be a new strategy for managing myocardial I/R injury. Here, we developed polydopamine nanoparticles (PDA NPs) as a new type of Ferroptosis inhibitor for cardioprotection. The PDA NPs features intriguing properties in inhibiting Fe²⁺ accumulation and restoring mitochondrial functions in H9c2 cells. Subsequently, we demonstrated that administration of PDA NPs effectively reduced Fe²⁺ deposition and lipid peroxidation in a myocardial I/R injury mouse model. In addition, the myocardial I/R injury in mice was alleviated by PDA NPs treatment, as demonstrated by reduced infarct size and improved cardiac functions. The present work indicates the therapeutic effects of PDA NPs against myocardial I/R injury via preventing Ferroptosis.