Engineered Macrophage Membrane‐Coated S100A9‐siRNA for Ameliorating Myocardial Ischemia‐Reperfusion Injury

Autor: He Lu, Junzhuo Wang, Ziwei Chen, Jing Wang, Yaohui Jiang, Zequn Xia, Ya Hou, Pingping Shang, Rutian Li, Yuyong Liu, Jun Xie
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Advanced Science, Vol 11, Iss 41, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2198-3844
91220564
DOI: 10.1002/advs.202403542
Popis: Abstract Despite the widespread adoption of emergency coronary reperfusion therapy, reperfusion‐induced myocardial injury remains a challenging issue in clinical practice. Following myocardial reperfusion, S100A8/A9 molecules are considered pivotal in initiating and regulating tissue inflammatory damage. Effectively reducing the S100A8/A9 level in ischemic myocardial tissue holds significant therapeutic value in salvaging damaged myocardium. In this study, HA (hemagglutinin)‐ and RAGE (receptor for advanced glycation end products)‐ comodified macrophage membrane‐coated siRNA nanoparticles (MMM/RNA NPs) with siRNA targeting S100A9 (S100A9‐siRNA) are successfully prepared. This nanocarrier system is able to target effectively the injured myocardium in an inflammatory environment while evading digestive damage by lysosomes. In vivo, migration of MMM/RNA NPs to myocardial injury lesions is confirmed in a myocardial ischemia‐reperfusion injury (MIRI) mouse model. Intravenous injection of MMM/RNA NPs significantly reduced S100A9 levels in serum and myocardial tissues, further decreasing myocardial infarction area and improving cardiac function. Targeted reduction of S100A8/A9 by genetically modified macrophage membrane‐coated nanoparticles may represent a new therapeutic intervention for MIRI.
Databáze: Directory of Open Access Journals
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