Department of Anesthesiology, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei 230601, PR China.
Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, 678 Furong Road, Hefei 230601, PR China.
Theranostics. 2022 Oct 17;12(17):7237-7249. doi: 10.7150/thno.77345. eCollection 2022.
: The only effective treatment for myocardial infarction (MI) is the timely restoration of coronary blood flow in the infarcted area, but further reperfusion exacerbates myocardial injury and leads to distal coronary no-reflow, which affects patient prognosis. Angiogenesis could be an important therapeutic strategy for re-establishing the blood supply to save the ischemic myocardium after MI. Basic fibroblast growth factor () has been shown to promote angiogenesis. However, direct intravenous administration of is not a viable option given its poor half-life . : Herein, we developed a peptide Lys-Lys-Pro-Leu-Gly-Leu-Ala-Gly-Phe-Phe () to encapsulate to form and proposed an enzyme-instructed self-assembly (EISA) strategy to deliver and slowly release in the ischemic myocardium. : The exerted a stronger cardioprotective effect than free in a rat model of myocardial ischemia-reperfusion (MI/R). results revealed that the could be cleaved by matrix metallopeptidase 9 (MMP-9) to yield through amphipathic changes. experiments indicated that intravenous administration of could lead to their restructuring into and long term retention of in the ischemic myocardium of rat due to high expression of MMP-9 and assembly-induced retention (AIR) effect, respectively. Twenty-eight days after MI/R model establishment, treatment significantly reduced fibrosis and improved cardiac function of the rats. We predict that our strategy could be applied in clinic for MI treatment in the future.
: 心肌梗死(MI)唯一有效的治疗方法是及时恢复梗死区域的冠状动脉血流,但进一步再灌注会加重心肌损伤,并导致远端冠状动脉无复流,影响患者预后。血管生成可能是一种重要的治疗策略,可重新建立血液供应,以挽救 MI 后的缺血心肌。碱性成纤维细胞生长因子()已被证明可促进血管生成。然而,由于其半衰期短,直接静脉内给予 不是可行的选择。: 在此,我们开发了一种肽 Lys-Lys-Pro-Leu-Gly-Leu-Ala-Gly-Phe-Phe()来包裹以形成,并提出了一种酶指导的自组装(EISA)策略,以在缺血心肌中递送电和缓慢释放。: 在心肌缺血再灌注(MI/R)大鼠模型中, 比游离 发挥了更强的心脏保护作用。 结果表明, 可以通过基质金属蛋白酶 9(MMP-9)的切割作用,通过两亲性变化产生 。 实验表明,由于 MMP-9 的高表达和组装诱导保留(AIR)效应,静脉给予 可导致其重构为 并在大鼠缺血心肌中长时间保留 。在 MI/R 模型建立 28 天后, 治疗显著减少了纤维化并改善了大鼠的心脏功能。: 我们预测,我们的策略将来可应用于临床 MI 治疗。