1. Academic Validation
  2. Spatiotemporal control of neutrophil fate to tune inflammation and repair for myocardial infarction therapy

Spatiotemporal control of neutrophil fate to tune inflammation and repair for myocardial infarction therapy

  • Nat Commun. 2024 Oct 1;15(1):8481. doi: 10.1038/s41467-024-52812-6.
Cheesue Kim # 1 Hyeok Kim # 2 3 Woo-Sup Sim # 2 3 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 7 8 9 Byung-Soo Kim 10 11 12 13 14
Affiliations

Affiliations

  • 1 School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea.
  • 2 Department of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul, Republic of Korea.
  • 3 Department of Internal Medicine, Seoul Saint Mary's Hospital, Seoul, Republic of Korea.
  • 4 Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, Republic of Korea.
  • 5 School of Health and Environmental Science, Korea University, Seoul, Republic of Korea.
  • 6 Department of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong.
  • 7 Department of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul, Republic of Korea. cardioman@catholic.ac.kr.
  • 8 Department of Internal Medicine, Seoul Saint Mary's Hospital, Seoul, Republic of Korea. cardioman@catholic.ac.kr.
  • 9 Cell Death Disease Research Center, The Catholic University of Korea, Seoul, Republic of Korea. cardioman@catholic.ac.kr.
  • 10 School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea. byungskim@snu.ac.kr.
  • 11 Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, Republic of Korea. byungskim@snu.ac.kr.
  • 12 Institute of Chemical Processes, Seoul National University, Seoul, Republic of Korea. byungskim@snu.ac.kr.
  • 13 Institute of Engineering Research, Seoul National University, Seoul, Republic of Korea. byungskim@snu.ac.kr.
  • 14 Bio-MAX Institute, Seoul National University, Seoul, Republic of Korea. byungskim@snu.ac.kr.
  • # Contributed equally.
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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