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微针介导的基因传递治疗缺血性心肌疾病。

Microneedle-mediated gene delivery for the treatment of ischemic myocardial disease.

机构信息

Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P. R. China.

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.

出版信息

Sci Adv. 2020 Jun 17;6(25):eaaz3621. doi: 10.1126/sciadv.aaz3621. eCollection 2020 Jun.

Abstract

Cardiovascular disorders are still the primary cause of mortality worldwide. Although intramyocardial injection can effectively deliver agents to the myocardium, this approach is limited because of its restriction to needle-mediated injection and the minor retention of agents in the myocardium. Here, we engineered phase-transition microneedles (MNs) coated with adeno-associated virus (AAV) and achieved homogeneous distribution of AAV delivery. Bioluminescence imaging revealed the successful delivery and transfection of AAV-luciferase. AAV-green fluorescent protein-transfected cardiomyocytes were homogeneously distributed on postoperative day 28. AAV-vascular endothelial growth factor (VEGF)-loaded MNs improved heart function by enhancing VEGF expression, promoting functional angiogenesis, and activating the Akt signaling pathway. The results indicated the superiority of MNs over direct muscle injection. Consequently, MNs might emerge as a promising tool with great versatility for delivering various agents to treat ischemic myocardial disease.

摘要

心血管疾病仍然是全球主要的死亡原因。虽然心肌内注射可以有效地将药物递送到心肌,但这种方法受到限制,因为它只能通过针介导注射,并且药物在心肌中的保留量较小。在这里,我们设计了具有相变的微针 (MN),并涂覆腺相关病毒 (AAV),实现了 AAV 传递的均匀分布。生物发光成像显示 AAV-荧光素酶的成功传递和转染。在术后第 28 天,AAV-绿色荧光蛋白转染的心肌细胞均匀分布。载有血管内皮生长因子 (VEGF) 的 AAV 负载 MN 通过增强 VEGF 表达、促进功能性血管生成和激活 Akt 信号通路来改善心脏功能。结果表明 MN 优于直接肌肉注射。因此,MN 可能成为一种很有前途的工具,具有很大的通用性,可用于递送至缺血性心肌疾病的各种药物。

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