Intercellular NETwork-facilitated sarcoplasmic reticulum targeting for myocardial ischemia-reperfusion injury treatment

• DOI: 10.1126/sciadv.adr4333
• Publication Date: 2025-02-12T18:58:36Z
• Authors: Peihang Jiang; Fangyang Huang; Liqiang Chen; Hao Zhou; Yudi Deng; Lian Li; Mao Chen; Yuan Huang
• Keywords: SERCA; Crosstalk

Myocardial ischemia-reperfusion injury (MIRI) often leads to irreversible myocardium dysfunction, while existing therapies are palliatives that transiently alleviate the disease symptoms. Repairing sarcoplasmic reticulum Ca 2+ -ATPase (SERCA) could reverse MIRI, which, however, requires precise drug delivery (SR). To this end, we leverage cell-cell “NETwork” of neutrophils deliver SERCA activator-loaded SR-localized nanoparticles (L-P-NPs) damaged myocardial cells, following a hierarchical targeting process: (i) chemotactic L-P-NPs ischemia-reperfused heart, achieving tissue level targeting; (ii) produce neutrophil extracellular traps (NETs) transport injured cell, cellular (iii) escort therapeutic payloads SR, subcellular targeting. We showed platform profoundly restored activity, augmented cardiac function, and ameliorated adverse heart remodeling. Our study provides insight into direct restoration SR for effective treatment MIRI other muscle diseases.