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负载五倍子酰葡萄糖的纳米颗粒的全身递送可保护大鼠弹性层并预防腹主动脉瘤。

Systemic Delivery of Nanoparticles Loaded with Pentagalloyl Glucose Protects Elastic Lamina and Prevents Abdominal Aortic Aneurysm in Rats.

作者信息

Nosoudi Nasim, Chowdhury Aniqa, Siclari Steven, Parasaram Vaideesh, Karamched Saketh, Vyavahare Naren

机构信息

Clemson University, Clemson, SC, USA.

出版信息

J Cardiovasc Transl Res. 2016 Dec;9(5-6):445-455. doi: 10.1007/s12265-016-9709-x. Epub 2016 Aug 19.

Abstract

Degeneration of elastin plays a vital role in the pathology and progression of abdominal aortic aneurysm (AAA). Our previous study showed that pentagalloyl glucose (PGG), a core derivative of tannic acid, hinders the development of AAAs in a clinically relevant animal model when applied locally. In this study, we tested whether targeted nanoparticles (NPs) can deliver PGG to the site of an aneurysm and prevent aneurysmal growth by protecting elastin. PGG-loaded albumin NPs with a surface-conjugated elastin-specific antibody were prepared. Aneurysms were induced by calcium chloride-mediated injury to the abdominal aorta in rats. NPs were injected into the tail vein after 10 days of CaCl injury. Rats were euthanized after 38 days. PGG delivery led to reduction in macrophage recruitment, matrix metalloproteinase (MMP) activity, elastin degradation, calcification, and development of aortic aneurysm. Such NP delivery offers the potential for the development of effective and safe therapies for AAA.

摘要

弹性蛋白的退化在腹主动脉瘤(AAA)的病理过程和进展中起着至关重要的作用。我们之前的研究表明,五倍子酰葡萄糖(PGG)是单宁酸的一种核心衍生物,在临床相关动物模型中局部应用时可抑制AAA的发展。在本研究中,我们测试了靶向纳米颗粒(NPs)是否能将PGG递送至动脉瘤部位,并通过保护弹性蛋白来预防动脉瘤生长。制备了表面偶联弹性蛋白特异性抗体的载PGG白蛋白纳米颗粒。通过氯化钙介导大鼠腹主动脉损伤诱导动脉瘤形成。在氯化钙损伤10天后将纳米颗粒注入尾静脉。38天后对大鼠实施安乐死。PGG的递送导致巨噬细胞募集减少、基质金属蛋白酶(MMP)活性降低、弹性蛋白降解减少、钙化减少以及主动脉瘤发展减缓。这种纳米颗粒递送为开发有效且安全的AAA治疗方法提供了可能性。

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