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聚多巴胺包覆的蒙脱石微片作为治疗平台,通过抑制氧化应激修复小鼠结肠炎的肠道黏膜屏障。

Polydopamine-cladded montmorillonite micro-sheets as therapeutic platform repair the gut mucosal barrier of murine colitis through inhibiting oxidative stress.

作者信息

Lin Gaolong, Yu Fengnan, Li Dingwei, Chen Yi, Zhang Mengjiao, Lu Kaili, Wang Neili, Hu Sunkuan, Zhao Yingzheng, Xu Helin

机构信息

Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325035, China.

CiXi Biomedical Research Institute of Wenzhou Medical University, China.

出版信息

Mater Today Bio. 2023 May 3;20:100654. doi: 10.1016/j.mtbio.2023.100654. eCollection 2023 Jun.

Abstract

Montmorillonite (MMT), a layered aluminosilicate, has a mucosal nutrient effect and restores the gut barriers integrity. However, orally administrating MMT is not effective to combat the reactive oxygen species (ROS) and alleviate the acute inflammatory relapse for colitis patients. Herein, polydopamine-doped montmorillonite micro-sheets (PDA/MMT) have been developed as a therapeutic platform for colitis treatment. SEM and EDS analysis showed that dopamine monomer (DA) was easily polymerized in alkaline condition and polydopamine (PDA) was uniformly cladded on the surface of MMT micro-sheets. The depositing amount of PDA was reaching to 2.06 ​± ​0.08%. Moreover, fluorescence probes experiments showed that PDA/MMT presented the broad spectra of scavenging various ROS sources including •OH, •O, and HO. Meanwhile, the intracellular ROS of Rosup/HO treated Caco-2 ​cell was also effectively scavenged by PDA/MMT, which resulted in the obvious improvement of the cell viability under oxidative stress. Moreover, most of orally administrated PDA/MMT was transited to the gut and form a protective film on the diseased colon. PDA/MMT exhibited the obvious therapeutic effect on DSS-induced ulcerative colitis mouse. Importantly, the gut mucosa of colitis mouse was well restored after PDA/MMT treatment. Moreover, the colonic inflammation was significantly alleviated and the goblet cells were obliviously recovered. The therapeutic mechanism of PDA/MMT was highly associated with inhibiting oxidative stress. Collectively, PDA/MMT micro-sheets as a therapeutic platform may provide a promising therapeutic strategy for UC treatment.

摘要

蒙脱石(MMT)是一种层状铝硅酸盐,具有黏膜营养作用并能恢复肠道屏障的完整性。然而,口服MMT对对抗活性氧(ROS)和缓解结肠炎患者的急性炎症复发并无效果。在此,聚多巴胺掺杂的蒙脱石微片(PDA/MMT)已被开发为一种用于结肠炎治疗的治疗平台。扫描电子显微镜(SEM)和能谱分析(EDS)表明,多巴胺单体(DA)在碱性条件下易于聚合,聚多巴胺(PDA)均匀地包覆在MMT微片表面。PDA的沉积量达到2.06±0.08%。此外,荧光探针实验表明,PDA/MMT呈现出清除包括•OH、•O和HO等各种ROS来源的广谱特性。同时,PDA/MMT也有效清除了经Rosup/HO处理的Caco-2细胞内的ROS,这导致在氧化应激下细胞活力有明显改善。此外,口服的PDA/MMT大多转移至肠道并在患病结肠上形成保护膜。PDA/MMT对葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎小鼠表现出明显的治疗效果。重要的是,PDA/MMT治疗后,结肠炎小鼠的肠道黏膜得到良好恢复。此外,结肠炎症明显减轻,杯状细胞明显恢复。PDA/MMT的治疗机制与抑制氧化应激高度相关。总体而言,PDA/MMT微片作为一种治疗平台可能为溃疡性结肠炎(UC)的治疗提供一种有前景的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc7/10195987/96286d59b401/ga1.jpg

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