Mannose-rich Oligosaccharides-functionalized Selenium Nanoparticles Mediates Macrophage Reprogramming and Inflammation Resolution in Ulcerative Colitis

Mannose-rich Oligosaccharides-functionalized Selenium Nanoparticles Mediates Macrophage Reprogramming and Inflammation Resolution in Ulcerative Colitis
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富含甘露糖寡糖功能化硒纳米颗粒介导溃疡性结肠炎巨噬细胞重编程和炎症消退

DOI:
10.1016/j.cej.2021.131715
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发表时间:
2021-08
影响因子:
15.1
通讯作者:
ZhiHuang
ZhiHuang
中科院分区:
工程技术1区
文献类型:
--
作者:
Hui Yang;ChenghuiZhu;WenlinYuan;XianWei;Chang Liu;JiarunHuang;MengYuan;YanjunWu;QinjieLing;Peter R.Hoffmann;TianfengChen;ZhiHuang

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炎症性肠病(IBD)是一种全球性疾病,通常分为克罗恩病(CD)和溃疡性结肠炎(UC),炎症反应在其中起着关键作用。本论文通过酶法制备抗炎活性最强的富含甘露糖低聚糖(MRO)的生物活性成分,并将其应用于硒纳米颗粒(SeNPs)的功能化,旨在通过加速巨噬细胞的重新编程来解决UC的炎症。本研究以亚硒酸盐为原料,用抗坏血酸还原MRO法制备了SeNPs。MRO功能化明显提高了SeNPs的稳定性和生物相容性,使平均直径为70 nm的MRO(MRO-SeNPs)微球(2µM Se)在60d内保持稳定。此外,巨噬细胞对MRO-SeNPs的有效摄取是通过针对巨噬细胞受体的MRO的贡献来实现的。正如预期的那样,MRO-SeNPs在体外改善了巨噬细胞的重编程,从而导致了细胞因子表达的典型M2极化曲线。此外,在DSS诱导的小鼠结肠炎模型中,MRO-SeNPs通过原位抑制IL-1β、IL-6、肿瘤坏死因子-α、IL-12和单核细胞趋化蛋白-1等促炎性细胞因子而有效地减轻结肠炎,并在结肠组织中发挥显著的抗氧化作用。因此,MRO-SeNPs通过促进巨噬细胞重新编程而显示出治疗潜力,从而导致炎症消退。综上所述,本研究不仅为利用结构优化的MRO实现纳米药物功能化提供了策略,而且揭示了成功治疗IBD和其他肠道疾病的作用机制。
Inflammatory bowel disease (IBD) is a global disease and usually classified into Crohn’s disease (CD) and ulcerative colitis (UC), in which the inflammatory response is known to play a pivotal role. Herein, a bioactive component of mannose-rich oligosaccharides (MRO) was produced by enzymatic hydrolysis with most potent anti-inflammation and employed to functionalize selenium nanoparticles (SeNPs), aming to solve of inflammation in UC by accelerating the reprogramming of macrophages. In this study, SeNPs was prepared by selenite and MRO with ascorbic acid reduction. The stability and biocompatibility of SeNPs was obviously improved by the functionalization of MRO, resulting in spheres (2 µM Se) carrying around 26 ng/ml MRO (MRO-SeNPs) with an average diameter of 70 nm remained stable in 60 d. In addition, efficient cellular uptake of MRO-SeNPs in macrophages was detected by contribution of MRO targeted to the receptors of macrophages. As expected, MRO-SeNPs exhibited improvement of macrophage reprogrammingin vitro, thus leading to a typical M2 polarization profile of cytokine expression. Furthermore, in DSS-induced mouse colitis model, MRO-SeNPs effectively mitigated colitis by suppressing the pro-inflammatory such as IL-1β, IL-6, TNF-α, IL-12 and MCP-1 cytokinesin situ, and exerted salient antioxidant capacity in colon tissues. As a result, MRO-SeNPs exhibited therapeutic potential by promoting macrophages reprogramming leading to inflammation resolution. Taken together, this study not only provides strategy for functionalization of nanomedicines using structure-optimized MRO, but also reveals the action mechanism on successful treatment of IBD and other intestinal diseases.
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发表时间: 2019-01
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