Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, Missouri 63130, United States.
Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, Missouri 63130, United States.
ACS Nano. 2022 Nov 22;16(11):19551-19566. doi: 10.1021/acsnano.2c10043. Epub 2022 Nov 11.
Myocardial infarction (MI) causes massive cell death due to restricted blood flow and oxygen deficiency. Rapid and sustained oxygen delivery following MI rescues cardiac cells and restores cardiac function. However, current oxygen-generating materials cannot be administered during acute MI stage without direct injection or suturing methods, both of which risk rupturing weakened heart tissue. Here, we present infarcted heart-targeting, oxygen-releasing nanoparticles capable of being delivered by intravenous injection at acute MI stage, and specifically accumulating in the infarcted heart. The nanoparticles can also be delivered before MI, then gather at the injured area after MI. We demonstrate that the nanoparticles, delivered either pre-MI or post-MI, enhance cardiac cell survival, stimulate angiogenesis, and suppress fibrosis without inducing substantial inflammation and reactive oxygen species overproduction. Our findings demonstrate that oxygen-delivering nanoparticles can provide a nonpharmacological solution to rescue the infarcted heart during acute MI and preserve heart function.
心肌梗死 (MI) 会因血流受限和缺氧而导致大量细胞死亡。MI 后快速持续供氧可挽救心脏细胞并恢复心脏功能。然而,目前的供氧材料在没有直接注射或缝合方法的情况下不能在急性 MI 阶段使用,这两种方法都有破裂脆弱心肌组织的风险。在这里,我们提出了针对心肌梗死的、能够通过静脉注射在急性 MI 阶段给药的、并能特异性地在梗死心脏中积累的释氧纳米颗粒。这些纳米颗粒也可以在 MI 之前给药,然后在 MI 后聚集在损伤区域。我们证明,无论是在 MI 前还是 MI 后给药,这些纳米颗粒都能提高心脏细胞的存活率、刺激血管生成,并抑制纤维化,而不会引起大量炎症和活性氧过度产生。我们的研究结果表明,供氧纳米颗粒可为急性 MI 期间挽救梗死心脏和保护心脏功能提供一种非药物解决方案。