A Novel Nanomedicine Ameliorates Acute Inflammatory Bowel Disease by Regulating Macrophages and T-Cells,Molecular Pharmaceutics

当前位置： X-MOL 学术 › Mol. Pharmaceutics › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

A Novel Nanomedicine Ameliorates Acute Inflammatory Bowel Disease by Regulating Macrophages and T-Cells
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2021-07-26 , DOI: 10.1021/acs.molpharmaceut.1c00415
Zian Feng _{1,

2} , Lina Jiao _{1,

2} , Zhiyong Wu ₃ , Jiameng Xu _{1,

2} , Pengfei Gu _{1,

2} , Shuwen Xu _{1,

2} , Zhenguang Liu _{1,

2} , Yuanliang Hu _{1,

2} , Jiaguo Liu _{1,

2} , Yi Wu _{1,

2} , Deyun Wang _{1,

2}

Affiliation

Ramulus mori polysaccharide (RMP), one of the most important active components of R. mori, has been attracting increasing interest because of its potent bioactive properties, including anti-inflammatory, antitumor, and antidiabetic effects. Despite the great therapeutic potential of RMP, its inherent properties of low bioavailability and brief biological half-life have limited its applications to the clinic. Thus, RMP was packaged by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to develop a novel anti-inflammatory nanomedicine (PLGA-RMP) in this study. The nanoparticles were synthesized via a double-emulsion solvent evaporation technique, and the average diameter of PLGA-RMP was about 202 nm. PLGA-RMP nanoparticles reduced the expression of inflammatory cytokines while promoting the production of IL-10, and boosted the phenotypic shift in macrophages in vitro. Furthermore, lipopolysaccharide (LPS)-induced inflammatory bowel disease (IBD) in mouse was used to examine the anti-inflammatory effect of PLGA-RMP in vivo. Oral administration of PLGA-RMP in LPS-induced IBD mice substantially mitigated the intestinal inflammation compared to treatment with LPS alone, as evidenced by attenuation of disease activity index scores and inflammatory damage in the intestine. Meanwhile, PLGA-RMP suppressed the expression and secretion of specific inflammatory cytokines including TNF-α, IL-6, IL-1β, and PGE2 in the inflamed intestine while inhibiting the activation of CD3⁺CD8⁺ T-cells and increasing the number of activated T_regs in the intestine. These results indicated that PLGA-RMP deserves further consideration as a potential therapeutic nanomedicine to treat various inflammatory diseases, including IBD.

中文翻译：

一种新型纳米药物通过调节巨噬细胞和 T 细胞改善急性炎症性肠病

桑枝多糖 ( RMP ) 是桑树最重要的活性成分之一，由于其强大的生物活性特性，包括抗炎、抗肿瘤和抗糖尿病作用，引起了越来越多的关注。尽管 RMP 具有巨大的治疗潜力，但其生物利用度低和生物半衰期短的固有特性限制了其在临床上的应用。因此，RMP 由聚乳酸-乙醇酸）（PLGA）纳米颗粒在本研究中开发一种新型抗炎纳米药物（PLGA-RMP）。纳米粒子通过双乳液溶剂蒸发技术合成，PLGA-RMP的平均直径约为202 nm。PLGA-RMP 纳米颗粒降低了炎症细胞因子的表达，同时促进了 IL-10 的产生，并促进了体外巨噬细胞的表型转变。此外，使用脂多糖（LPS）诱导的小鼠炎症性肠病（IBD）来检测PLGA-RMP在体内的抗炎作用。与单独使用 LPS 治疗相比，在 LPS 诱导的 IBD 小鼠中口服 PLGA-RMP 可显着减轻肠道炎症，这可以通过肠道疾病活动指数评分和炎症损伤的减弱来证明。同时，⁺ CD8 ⁺ T 细胞并增加肠道中激活的 T _{regs的数量。}这些结果表明，PLGA-RMP 值得进一步考虑作为一种潜在的治疗性纳米药物，用于治疗包括 IBD 在内的各种炎症性疾病。

更新日期：2021-09-06

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11