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一种新型特异性适体在缺血性脑卒中后靶向脑血管内皮细胞。

A novel specific aptamer targets cerebrovascular endothelial cells after ischemic stroke.

机构信息

Department of Neurosurgery, McGovern School of Medicine, University of Texas Health Science Center, MSB 7.134, 6431 Fannin St., Houston, TX, 77030, USA.

Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, USA.

出版信息

Sci Rep. 2023 Jun 20;13(1):9990. doi: 10.1038/s41598-023-36993-6.

Abstract

Cell specific-targeted therapy (CSTT) for acute ischemic stroke remains underdeveloped. Cerebrovascular endothelial cells (CECs) are key components of the blood-brain barrier and are the first brain cells affected by ischemic stroke. After stroke, CEC injury causes insufficient energy supply to neurons and leads to cytotoxic and vasogenic brain edema. Aptamers are short single-stranded RNA or DNA molecules that can bind to specific ligands for cell specific delivery. The expression of vascular cell adhesion molecule-1 (VCAM-1) is increased on CECs after stroke. Herein, we report that an RNA-based VCAM-1-aptamer can specifically target CECs in stroke brains following transient middle cerebral artery occlusion in mice. Our data demonstrate the potential of an RNA-based aptamer as an effective delivery platform to target CECs after stroke. We believe this method will allow for the development of CSTT for treatment of patients with stroke.

摘要

细胞特异性靶向治疗(CSTT)在急性缺血性脑卒中中的应用仍不够发达。脑血管内皮细胞(CEC)是血脑屏障的关键组成部分,也是缺血性脑卒中最早受到影响的脑细胞。脑卒中后,CEC 损伤导致神经元能量供应不足,进而引发细胞毒性和血管源性脑水肿。适体是短的单链 RNA 或 DNA 分子,能够与特定的配体结合,实现细胞特异性递药。脑卒中后,CEC 上的血管细胞黏附分子-1(VCAM-1)表达增加。在此,我们报告了一种基于 RNA 的 VCAM-1 适体能特异性靶向在小鼠短暂性大脑中动脉闭塞后脑卒中大脑中的 CEC。我们的数据表明,基于 RNA 的适体作为一种有效的递药平台,具有靶向脑卒中后 CEC 的潜力。我们相信这种方法将为治疗脑卒中患者的 CSTT 提供可能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a45b/10282052/ae930f652542/41598_2023_36993_Fig1_HTML.jpg

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