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微流控封装锰有机骨架作为治疗炎症性肠病的模拟酶。

Microfluidic encapsulated manganese organic frameworks as enzyme mimetics for inflammatory bowel disease treatment.

机构信息

Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.

Department of Rheumatology and Immunology, Institute of Translational Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210002, China; State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.

出版信息

J Colloid Interface Sci. 2022 Feb;607(Pt 2):1382-1390. doi: 10.1016/j.jcis.2021.09.016. Epub 2021 Sep 8.

Abstract

Metal organic frameworks (MOFs) with physicochemical properties and adjustable structures have been proposed as very attractive materials. The studies on development of such functional materials tended to fabricate featured MOF objects with fascinating catalytic capabilities to utilize their biomedical values. In this paper, we present novel biocompatible manganese metal organic framework (Mn-MOF)-based catalase mimetics with microfluidic microcapsule encapsulation for intravital inflammatory bowel disease (IBD) treatment. Phosphoserine, a component of the cell membrane, served as an organic ligand to ensure biocompatibility of Mn-MOF. Owing to the core-shell structure of the microcapsule, the Mn-MOF exhibited a well-organized distribution and controlled release features, which could protect them from gastric juice and provide function in the intestine. Upon reaching the sites of the inflammatory bowel, Mn-MOF could effectively scavenge reactive oxygen species (ROS) over-produced by neutrophils and macrophages under various gastrointestinal pH environments, protecting intestinal epithelial cells from ROS damage. The Mn-MOF-encapsulated microcapsules exhibited high performances in treating spontaneous IBD in interleukin-10-deficient mice by relieving the oxidative stress, reducing the inflammation, and restoring the intestinal barrier. These results indicate that the functional Mn-MOF-encapsulated microcapsules have practical applications in the treatment of ROS-associated diseases.

摘要

金属有机骨架(MOFs)具有物理化学性质和可调节的结构,被认为是非常有吸引力的材料。开发这种功能材料的研究倾向于制造具有迷人催化能力的特色 MOF 物体,以利用它们的生物医学价值。在本文中,我们提出了一种新颖的基于生物相容的锰金属有机骨架(Mn-MOF)的过氧化氢模拟物,其具有微流控微胶囊封装,用于活体炎症性肠病(IBD)治疗。磷丝氨酸是细胞膜的组成部分,用作有机配体以确保 Mn-MOF 的生物相容性。由于微胶囊的核壳结构,Mn-MOF 表现出良好的分布和控制释放特性,可保护其免受胃液的影响,并在肠道中发挥作用。当到达炎症性肠病部位时,Mn-MOF 可以在各种胃肠道 pH 环境下有效清除中性粒细胞和巨噬细胞过度产生的活性氧(ROS),保护肠上皮细胞免受 ROS 损伤。Mn-MOF 封装的微胶囊在通过缓解氧化应激、减轻炎症和恢复肠道屏障来治疗白细胞介素-10 缺陷型小鼠自发 IBD 方面表现出优异的性能。这些结果表明,功能性 Mn-MOF 封装的微胶囊在治疗与 ROS 相关的疾病方面具有实际应用价值。

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