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基于聚酰胺-胺的递药载体的 miRNA 转染可预防低氧/再灌注诱导的心肌细胞凋亡。

miRNA transfection via poly(amidoamine)-based delivery vector prevents hypoxia/reperfusion-induced cardiomyocyte apoptosis.

机构信息

Nanobioscience, Agharkar Research Institute, Pune, 411 004, India.

Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, 400076, India.

出版信息

Nanomedicine (Lond). 2020 Jan;15(2):163-181. doi: 10.2217/nnm-2019-0363. Epub 2019 Dec 4.

Abstract

Myocardial infarction is a tissue injury that leads to apoptosis of cardiomyocytes. This can be prevented by using miRNAs, but its delivery to cardiomyocytes is a major hurdle. We aimed to deliver miRNAs using poly(amidoamine)-histidine (PAMAM-His) nanocarriers to prevent apoptosis. The PAMAM-His nanoparticles were synthesized and assessed for their transfection efficiency of miRNAs to prevent apoptosis in hypoxia/reperfusion-induced H9c2 as well as primary cultured cardiomyocytes. miRNAs-nanoparticle complexes exerted a significant antiapoptotic effect on the H9c2 and primary rat ventricular cardiomyocytes. Enhanced expression of antiapoptotic genes and decreased expression of proapoptotic genes were observed. PAMAM-His nanoparticles effectively delivered miRNAs to the cardiomyocytes and prevented the hypoxia/reperfusion-induced apoptosis critical in myocardial infarctions.

摘要

心肌梗死是一种导致心肌细胞凋亡的组织损伤。可以使用 miRNAs 来预防这种损伤,但将其递送到心肌细胞是一个主要的障碍。我们的目的是使用聚(酰胺-胺)-组氨酸(PAMAM-His)纳米载体来传递 miRNAs,以防止细胞凋亡。合成了 PAMAM-His 纳米颗粒,并评估了它们转染 miRNA 的效率,以防止缺氧/再灌注诱导的 H9c2 细胞以及原代培养的心肌细胞发生凋亡。miRNAs-纳米颗粒复合物对 H9c2 和原代大鼠心室心肌细胞具有显著的抗凋亡作用。观察到抗凋亡基因的表达增强,促凋亡基因的表达降低。PAMAM-His 纳米颗粒可有效将 miRNAs 递送到心肌细胞,并防止心肌梗死中关键的缺氧/再灌注诱导的细胞凋亡。

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