Immuno‐Nanocomplexes Target Heterogenous Network of Inflammation and Immunity in Myocardial Infarction

Autor: Fan Su, Weifan Ye, Yi Shen, Yujie Xie, Chong Zhang, Qianyun Zhang, Zhengqi Tang, Meihua Yu, Yu Chen, Bin He
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Advanced Science, Vol 11, Iss 36, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2198-3844
DOI: 10.1002/advs.202402267
Popis: Abstract Despite the proceeds in the management of acute myocardial infarction (AMI), the current therapeutic landscape still suffers from limited success in the clinic. Exaggerated inflammatory immune response and excessive oxidative stress are key pathological features aggravating myocardium damage. Herein, catalytic immunomodulatory nanocomplexes as anti‐AMI therapeutics to resolve reactive oxygen species (ROS)‐proinflammatory neutrophils‐specific‐inflammation is engineered. The nanocomplexes contain lyophilic S100A8/9 inhibitor ABR2575 in the core of nanoemulsions, which effectively disrupts the neutrophils‐S100A8/A9‐inflammation signaling pathway in the AMI microenvironment. Additionally, ROS scavenger ultrasmall CuxO nanoparticles are incorporated into the nanoemulsions via coordinating with SH groups of poly(ethylene glycol) (PEG)‐conjugated lipids, which mimic multiple enzymes, dramatically alleviating the oxidative stress damage to myocardial tissue. This combination strategy significantly suppresses the infiltration of pro‐inflammatory monocytes, macrophages, and neutrophils, as well as the secretion of inflammatory cytokines. Additionally, it potentially triggers cardiac Tert activation, which promotes myocardial function and decreases infarction size in preclinical murine AMI models. This approach offers a new nanomedicine for treating AMI, resulting in a dramatically enhanced therapeutic outcome.
Databáze: Directory of Open Access Journals
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