Department of Pharmaceutics, School of Pharmacy, Air Force Medical University, Changle West Road 169, Xi'an, 710032, Shaanxi, China.
Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Air Force Medical University, Xi'an, 710032, China.
J Nanobiotechnology. 2022 Jun 3;20(1):251. doi: 10.1186/s12951-022-01445-2.
At present, patients with myocardial infarction remain an increased risk for myocardial ischemia/reperfusion injury (MI/RI). There lacks effectively method to treat MI/RI in clinic. For the treatment of MI/RI, it is still a bottleneck to effectively deliver drug to ischemic myocardium. In this paper, a regulatory T cells (Tregs) biomimetic nanoparticle (CsA@PPTK) was prepared by camouflaging nanoparticle with platelet membrane.
CsA@PPTK actively accumulated in ischemic myocardium of MI/RI mice. CsA@PPTK significantly scavenged reactive oxygen species (ROS) and increased the generation of Tregs and the ratio of M2 type macrophage to M1 type macrophage in ischemic myocardium. Moreover, CsA@PPTK significantly attenuated apoptosis of cardiomyocytes and reduced the infarct size and fibrosis area in ischemic myocardium. CsA@PPTK markedly decreased the protein expression of MMP-9 and increased the protein expression of CX43 in ischemic myocardium tissue. Subsequently, the remodeling of the left ventricle was significant alleviated, and heart function of MI/RI mice was markedly improved.
CsA@PPTK showed significant therapeutic effect on MI/RI, and it has great potential application in the treatment of MI/RI.
目前,心肌梗死患者仍然存在心肌缺血/再灌注损伤(MI/RI)的风险增加。临床上缺乏有效的治疗 MI/RI 的方法。对于 MI/RI 的治疗,将药物有效递送到缺血心肌仍然是一个瓶颈。在本文中,通过将纳米颗粒伪装成血小板膜,制备了调节性 T 细胞(Tregs)仿生纳米颗粒(CsA@PPTK)。
CsA@PPTK 在 MI/RI 小鼠的缺血心肌中主动积聚。CsA@PPTK 可显著清除活性氧(ROS),增加缺血心肌中 Tregs 的产生和 M2 型巨噬细胞与 M1 型巨噬细胞的比例。此外,CsA@PPTK 可显著减轻心肌细胞凋亡,减少缺血心肌中的梗死面积和纤维化面积。CsA@PPTK 明显降低了缺血心肌组织中 MMP-9 的蛋白表达,增加了 CX43 的蛋白表达。随后,左心室重构明显缓解,MI/RI 小鼠的心功能明显改善。
CsA@PPTK 对 MI/RI 具有显著的治疗作用,在 MI/RI 的治疗中具有很大的应用潜力。