2. Academic Validation
  3. Peroxynitrite-Free Nitric Oxide-Embedded Nanoparticles Maintain Nitric Oxide Homeostasis for Effective Revascularization of Myocardial Infarcts

Peroxynitrite-Free Nitric Oxide-Embedded Nanoparticles Maintain Nitric Oxide Homeostasis for Effective Revascularization of Myocardial Infarcts

  • ACS Nano. 2024 Nov 26;18(47):32650-32671. doi: 10.1021/acsnano.4c10118.
Jiaxiong Zhang 1 2,  Shuya Wang 3 4,  Quan Sun 1 2,  Jian Zhang 1,  Xiaojing Shi 3 4,  Meilian Yao 1,  Jing Chen 1,  Qiong Huang 5,  Guogang Zhang 1 2 6,  Qun Huang 7,  Kelong Ai 3 4,  Yongping Bai 1 2
Affiliations

Affiliations

  • 1 Department of Geriatric Medicine, Coronary Circulation Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
  • 2 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
  • 3 Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, PR China.
  • 4 Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, PR China.
  • 5 Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
  • 6 Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410000, PR China.
  • 7 Department of Child Health Care, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan 410008, PR China.
PMID: 39545833 DOI: 10.1021/acsnano.4c10118
Abstract

Revascularization is crucial for treating myocardial infarction (MI). Nitric oxide (NO), at an appropriate concentration, is recognized as an ideal and potent pro-angiogenic factor. However, the application of NO in the treatment of MI is limited. Improper NO supplementation is harmful to revascularization because NO is converted into harmful peroxynitrite (ONOO-) in MI tissues with high Reactive Oxygen Species (ROS) levels. We overcome these obstacles by embedding biliverdin and NO into Prussian blue (PB) nanolattices to obtain an ONOO--free NO-embedded nanomedicine (OFEN). Unlike previous NO donors, OFEN provides NO stably and spontaneously for a longer time (>7 days), which makes it possible to maintain a stable concentration of NO, suitable for angiogenesis, through dose optimization. More importantly, based on the synergy between PB and biliverdin, OFEN converts ROS into beneficial O2 and inhibits the production of ONOO- from the source. OFEN specifically targets MI tissues and achieves sustained and stable NO delivery at the MI site. OFEN effectively promotes revascularization in the MI tissue, significantly reduces myocardial death and fibrosis, and ultimately promotes the complete recovery of cardiac function. Our strategy provides a promising approach for the treatment of myocardial and Other ischemic diseases.

Keywords

NO donor drugs; Prussian blue nanolattices; myocardial infarction; oxidative stress; revascularization.

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