Department of Geriatric Medicine, Coronary Circulation Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
ACS Nano. 2024 Nov 26;18(47):32650-32671. doi: 10.1021/acsnano.4c10118. Epub 2024 Nov 15.
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 O 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.
再血管化对于治疗心肌梗死(MI)至关重要。一氧化氮(NO)在适当的浓度下被认为是一种理想的、有效的促血管生成因子。然而,NO 在 MI 治疗中的应用受到限制。在活性氧(ROS)水平较高的 MI 组织中,NO 转化为有害的过氧亚硝酸盐(ONOO),因此不当的 NO 补充对再血管化是有害的。我们通过将胆红素和 NO 嵌入普鲁士蓝(PB)纳米晶格中来克服这些障碍,从而获得无 ONOO 的 NO 嵌入纳米药物(OFEN)。与以前的 NO 供体不同,OFEN 能够稳定且自发地提供更长时间(>7 天)的 NO,这使得通过剂量优化有可能维持适合血管生成的稳定 NO 浓度。更重要的是,基于 PB 和胆红素之间的协同作用,OFEN 将 ROS 转化为有益的 O,从源头上抑制 ONOO 的产生。OFEN 特异性靶向 MI 组织,并在 MI 部位实现持续且稳定的 NO 传递。OFEN 有效地促进 MI 组织的再血管化,显著减少心肌死亡和纤维化,并最终促进心脏功能的完全恢复。我们的策略为治疗心肌和其他缺血性疾病提供了一种有前途的方法。
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