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Engineered biomimetic nanovesicles show intrinsic anti-inflammatory properties for the treatment of inflammatory bowel diseases
Nanoscale ( IF 5.8 ) Pub Date : 2017-09-14 00:00:00 , DOI: 10.1039/c7nr04734g Claudia Corbo 1, 2, 3, 4 , Walter E. Cromer 4, 5, 6, 7, 8 , Roberto Molinaro 1, 2, 3, 4 , Naama E. Toledano Furman 1, 2, 3, 4 , Kelly A. Hartman 1, 2, 3, 4 , Enrica De Rosa 2, 3, 4, 9 , Christian Boada 1, 2, 3, 4, 10 , Xin Wang 1, 2, 3, 4 , David C. Zawieja 4, 5, 6, 7, 8 , Marco Agostini 11, 12, 13, 14, 15 , Francesco Salvatore 15, 16, 17 , Bincy P. Abraham 3, 4, 18, 19 , Ennio Tasciotti 1, 2, 3, 4, 20
Nanoscale ( IF 5.8 ) Pub Date : 2017-09-14 00:00:00 , DOI: 10.1039/c7nr04734g Claudia Corbo 1, 2, 3, 4 , Walter E. Cromer 4, 5, 6, 7, 8 , Roberto Molinaro 1, 2, 3, 4 , Naama E. Toledano Furman 1, 2, 3, 4 , Kelly A. Hartman 1, 2, 3, 4 , Enrica De Rosa 2, 3, 4, 9 , Christian Boada 1, 2, 3, 4, 10 , Xin Wang 1, 2, 3, 4 , David C. Zawieja 4, 5, 6, 7, 8 , Marco Agostini 11, 12, 13, 14, 15 , Francesco Salvatore 15, 16, 17 , Bincy P. Abraham 3, 4, 18, 19 , Ennio Tasciotti 1, 2, 3, 4, 20
Affiliation
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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.
中文翻译：
工程化的仿生纳米囊泡具有内在的抗炎特性，可用于治疗炎症性肠病
包括克罗恩氏病和溃疡性结肠炎在内的炎症性肠病（IBD）是胃肠道（GI）的慢性炎症。目前，它用免疫抑制剂或生物制剂治疗，这些制剂通常会引起严重的不良反应。因此，迫切需要更具体的治疗方法。为了为IBD治疗提供有效的治疗工具，在这项工作中，我们通过操纵白细胞膜来开发仿生纳米囊泡，以利用炎症过程中T细胞募集的机制。T淋巴细胞的一部分通过过表达α4β7整联蛋白参与归巢于胃肠道发炎的组织，该整联蛋白负责与其在内皮膜上的黏膜膜壁蛋白细胞粘附分子1的受体结合。基于这一原理，我们设计了仿生囊泡，称为专门的白细胞（SLKs），它们是在纯化的免疫细胞中过度诱导的白细胞样载体，其中掺有α4β7整联蛋白。我们在硫酸右旋糖酐钠诱导的IBD体内小鼠模型。值得注意的是，用SLKs治疗IBD小鼠可使我们观察到炎症的减轻（促炎和抗炎基因的良好调节，以及免疫细胞向结肠组织的浸润的减少），以及随之而来的肠道修复的增强（上皮损害低）。在这项研究中，我们证明了生物来源的纳米颗粒不仅可以用作天然靶向药物递送系统，而且还可以用作具有固有抗炎特性的纳米治疗剂。
更新日期：2017-09-21
中文翻译：
工程化的仿生纳米囊泡具有内在的抗炎特性，可用于治疗炎症性肠病
包括克罗恩氏病和溃疡性结肠炎在内的炎症性肠病（IBD）是胃肠道（GI）的慢性炎症。目前，它用免疫抑制剂或生物制剂治疗，这些制剂通常会引起严重的不良反应。因此，迫切需要更具体的治疗方法。为了为IBD治疗提供有效的治疗工具，在这项工作中，我们通过操纵白细胞膜来开发仿生纳米囊泡，以利用炎症过程中T细胞募集的机制。T淋巴细胞的一部分通过过表达α4β7整联蛋白参与归巢于胃肠道发炎的组织，该整联蛋白负责与其在内皮膜上的黏膜膜壁蛋白细胞粘附分子1的受体结合。基于这一原理，我们设计了仿生囊泡，称为专门的白细胞（SLKs），它们是在纯化的免疫细胞中过度诱导的白细胞样载体，其中掺有α4β7整联蛋白。我们在硫酸右旋糖酐钠诱导的IBD体内小鼠模型。值得注意的是，用SLKs治疗IBD小鼠可使我们观察到炎症的减轻（促炎和抗炎基因的良好调节，以及免疫细胞向结肠组织的浸润的减少），以及随之而来的肠道修复的增强（上皮损害低）。在这项研究中，我们证明了生物来源的纳米颗粒不仅可以用作天然靶向药物递送系统，而且还可以用作具有固有抗炎特性的纳米治疗剂。
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