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使用模拟炎症部位附近内皮表面的肽功能化纳米结构材料对表达α4β1整合素(VLA-4)的细胞进行选择性检测。

Selective detection of α4β1 integrin (VLA-4)-expressing cells using peptide-functionalized nanostructured materials mimicking endothelial surfaces adjacent to inflammatory sites.

作者信息

De Marco Rossella, Greco Arianna, Calonghi Natalia, Dattoli Samantha D, Baiula Monica, Spampinato Santi, Picchetti Pierre, De Cola Luisa, Anselmi Michele, Cipriani Francesca, Gentilucci Luca

机构信息

Department of Chemistry "G. Ciamician", University of Bologna, via Selmi 2, Bologna, 40126, Italy.

Department of Pharmacy and Biotechnology, University of Bologna, via Irnerio 48, Bologna, 40126, Italy.

出版信息

Biopolymers. 2017 Nov 27. doi: 10.1002/bip.23081.

Abstract

Persistent accumulation of immune cells mediated by α4β1 integrin (VLA-4) is a hallmark of the inflammatory diseases and of chronic inflammation observed in the affected tissues of autoimmune diseases. Aiming at exploring new methods for monitoring the course of the inflammatory processes, we designed the first peptide-functionalized nanostructured devices capable to mimic the high-density multivalency binding between the α4β1 integrin-expressing cells and the ligands overexpressed on the endothelial surfaces, in the proximity of the sites of inflammation. Specifically, we describe the first examples of monolayers constituted by dye-loaded zeolite L crystals, coated with α4β1 integrin peptide ligands, and we analyze the adhesion of model Jurkat cells in comparison to non-α4β1 integrin-expressing cells. In particular, the peptidomimetic diphenylurea-Leu-Asp-Val-diamine allows significant and selective detection of α4β1 integrin-expressing Jurkat cells, after very rapid incubation time, supporting the possible implementation in a diagnostic device capable to detect the desired cells from biological fluids, obtainable from patients in a noninvasive way.

摘要

由α4β1整合素(VLA - 4)介导的免疫细胞持续积累是炎症性疾病以及自身免疫性疾病受累组织中观察到的慢性炎症的一个标志。为了探索监测炎症过程进程的新方法,我们设计了首个肽功能化的纳米结构装置,该装置能够模拟表达α4β1整合素的细胞与炎症部位附近内皮表面上过度表达的配体之间的高密度多价结合。具体而言,我们描述了由负载染料的L型沸石晶体构成的单层的首个实例,这些晶体涂覆有α4β1整合素肽配体,并且我们分析了模型Jurkat细胞与不表达α4β1整合素的细胞相比的黏附情况。特别地,肽模拟物二苯基脲 - 亮氨酸 - 天冬氨酸 - 缬氨酸 - 二胺在极短的孵育时间后就能对表达α4β1整合素的Jurkat细胞进行显著且选择性的检测,这支持了其在能够从生物流体中检测所需细胞的诊断装置中的可能应用,而生物流体可以通过非侵入性方式从患者获取。

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