Genistein-Derived ROS-Responsive Nanoparticles Relieve Colitis by Regulating Mucosal Homeostasis

文献类型： 外文期刊

第一作者： Fan, Wentao

作者： Fan, Wentao;Zhang, Shuo;Wu, Yuting;Liu, Jiwen;Cao, Xiuyun;Liu, Shuhui;Yan, Liping;Song, Suquan;Lu, Tao;Huang, Chaobo;Cao, Xiuyun;Yan, Liping;Cao, Xiuyun;Yan, Liping;Shi, Xizhi;Liu, Guangliang

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关键词： colitis; mucosal homeostasis; ROS-responsive; nanoparticles; genistein

期刊名称：ACS APPLIED MATERIALS & INTERFACES （ 影响因子：9.229； 五年影响因子：9.57 ）

ISSN： 1944-8244

年卷期： 2021 年 13 卷 34 期

页码：

收录情况： SCI

摘要： Disruption of intestinal homeostasis is an important event in the development of inflammatory bowel disease (IBD), and genistein (GEN) is a candidate medicine to prevent IBD. However, the clinical application of GEN is restricted owing to its low oral bioavailability. Herein, a reactive oxygen species (ROS)-responsive nanomaterial (defined as GEN-NP2) containing superoxidase dismutase-mimetic temporally conjugated beta-cyclodextrin and 4-(hydroxymethyl)phenylboronic acid pinacol ester-modified GEN was prepared. GEN-NP2 effectively delivered GEN to the inflammation site and protected GEN from rapid metabolism and elimination in the gastrointestinal tract. In response to high ROS levels, GEN was site-specifically released and accumulated at inflammatory sites. Mechanistically, GEN-NP2 effectively increased the expression of estrogen receptor beta (ER beta), simultaneously reduced the expression of proinflammatory mediators (apoptosis-associated speck-like protein containing a CARD (ASC) and Caspase1-p20), attenuated the infiltration of inflammatory cells, promoted autophagy of intestinal epithelial cells, inhibited the secretion of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), modulated the gut microbiota, and ultimately alleviated colitis. In addition, the oral administration of these nanoparticles showed excellent safety, thereby providing confidence in the further development of precise treatments for IBD.

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