한빛사논문
Cheesue Kim 1,11, Hyeok Kim 2,3,11, Woo-Sup Sim 2,3,11, Mungyo Jung 1, Jihye Hong 4, Sangjun Moon 1, Jae-Hyun Park 2,3, Jin-Ju Kim 2,3, Mikyung Kang 5, Sungpil Kwon 1, Mi-Jeong Kim 3, Kiwon Ban 6, Hun-Jun Park 2,3,7,* & Byung‐Soo Kim 1,4,8,9,10,*
1School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea.
2Department of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul, Republic of Korea.
3Department of Internal Medicine, Seoul Saint Mary’s Hospital, Seoul, Republic of Korea.
4Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, Republic of Korea.
5School of Health and Environmental Science, Korea University, Seoul, Republic of Korea.
6Department of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong.
7Cell Death Disease Research Center, The Catholic University of Korea, Seoul, Republic of Korea.
8Institute of Chemical Processes, Seoul National University, Seoul, Republic of Korea.
9Institute of Engineering Research, Seoul National University, Seoul, Republic of Korea.
10Bio-MAX Institute, Seoul National University, Seoul, Republic of Korea.
11These authors contributed equally: Cheesue Kim, Hyeok Kim, Woo-Sup Sim.
*Corresponding authors: correspondence to Hun-Jun Park or Byung‐Soo Kim
Abstract
Neutrophils are critical mediators of both the initiation and resolution of inflammation after myocardial infarction (MI). Overexuberant neutrophil signaling after MI exacerbates cardiomyocyte apoptosis and cardiac remodeling while neutrophil apoptosis at the injury site promotes macrophage polarization toward a pro-resolving phenotype. Here, we describe a nanoparticle that provides spatiotemporal control over neutrophil fate to both stymie MI pathogenesis and promote healing. Intravenous injection of roscovitine/catalase-loaded poly(lactic-co-glycolic acid) nanoparticles after MI leads to nanoparticle uptake by circulating neutrophils migrating to the infarcted heart. Activated neutrophils at the infarcted heart generate reactive oxygen species, triggering intracellular release of roscovitine, a cyclin-dependent kinase inhibitor, from the nanoparticles, thereby inducing neutrophil apoptosis. Timely apoptosis of activated neutrophils at the infarcted heart limits neutrophil-driven inflammation, promotes macrophage polarization toward a pro-resolving phenotype, and preserves heart function. Modulating neutrophil fate to tune both inflammatory and reparatory processes may be an effective strategy to treat MI.
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