Targeting Efferocytosis with Carbonized Polymer Dots from a Natural Anti-Inflammatory Drug to Alleviate Excessive Inflammatory Responses in the Acute Phase of Myocardial Infarction

Excessive inflammation serves as a central pathological driver of adverse outcomes following myocardial infarction (MI). However, current anti-inflammatory interventions have demonstrated limited efficacy and safety in clinical trials. A key instigator of secondary inflammatory cascades post-MI is impaired efferocytosis—the insufficient recognition and clearance of apoptotic cells by macrophages. Concurrently, NLRP3/Caspase-1/GSDMD-mediated pyroptosis exacerbates both acute and persistent inflammatory responses. Modulating efferocytosis to suppress pyroptosis thus represents a promising therapeutic strategy for managing acute-phase inflammation. In this study, we developed pharmacologically active carbonized polymer dots derived from the natural anti-inflammatory drug curcumin (Cur-CPDs) with high water dispersibility and biocompatibility to modulate post-MI inflammation. Compared with free curcumin, Cur-CPDs significantly enhanced efferocytosis and facilitated inflammation resolution by activating the NOTCH-1/CD47 signaling pathway. Both in vitro and in vivo experiments revealed that Cur-CPDs restored the clearance of apoptotic cardiomyocytes, suppressed pyroptotic activation, and improved cardiac function during the early phase of MI. Collectively, these findings establish Cur-CPDs as a novel class of bioactive nanotherapeutics and underscore efferocytosis modulation as a viable target for mitigating residual inflammation and limiting cardiac injury following MI.