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Engineered biomimetic nanovesicles show intrinsic anti-inflammatory properties for the treatment of inflammatory bowel diseases

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Abstract

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a chronic inflammatory condition of the gastrointestinal (GI) tract. Currently, it is treated with immunosuppressant or biologics that often induce severe adverse effects. Thus, there is an urgent clinical need for more specific treatments. To provide a valid therapeutic tool for IBD therapy, in this work we developed biomimetic nanovesicles by manipulating leukocyte membranes to exploit mechanisms of T-cell recruitment during inflammation. A subset of T-lymphocytes participates in homing to inflamed tissue in the gastrointestinal tract by overexpressing the α4β7 integrin, which is responsible for binding to its receptor on the endothelial membrane, the mucosal addressin cell adhesion molecule 1. Based on this principle, we engineered biomimetic vesicles, referred to as specialized leukosomes (SLKs), which are leukocyte-like carriers ‘doped’ with the α4β7 integrin over-induced in purified immune cells. We tested SLKs in an in vivo murine model of IBD induced by treatment with dextran sulfate sodium. Notably, treatment of IBD mice with SLKs allowed us to observe a reduction of inflammation (favorable modulation of both pro- and anti-inflammatory genes, as well as reduction of immune cells infiltration into the colon tissue), and a consequent enhanced intestinal repair (low epithelial damage). In this study, we demonstrate that biological-derived nanoparticles can be used not only as naturally targeted drug delivery systems, but also as nano-therapeutics endowed with intrinsic anti-inflammatory properties.

Graphical abstract: Engineered biomimetic nanovesicles show intrinsic anti-inflammatory properties for the treatment of inflammatory bowel diseases

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Publication details

The article was received on 30 Jun 2017, accepted on 13 Sep 2017 and first published on 14 Sep 2017


Article type: Paper
DOI: 10.1039/C7NR04734G
Citation: Nanoscale, 2017, Advance Article
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    Engineered biomimetic nanovesicles show intrinsic anti-inflammatory properties for the treatment of inflammatory bowel diseases

    C. Corbo, W. E. Cromer, R. Molinaro, N. E. Toledano Furman, K. A. Hartman, E. De Rosa, C. Boada, X. Wang, D. C. Zawieja, M. Agostini, F. Salvatore, B. P. Abraham and E. Tasciotti, Nanoscale, 2017, Advance Article , DOI: 10.1039/C7NR04734G

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