纳米团簇
炎症性肠病
巨噬细胞极化
炎症
癌症研究
奥兰诺芬
结肠炎
巨噬细胞
结直肠癌
重编程
癌变
体内
免疫学
医学
细胞生物学
化学
生物
癌症
体外
疾病
纳米技术
材料科学
细胞
内科学
生物化学
类风湿性关节炎
生物技术
作者
Lu Cao,Liyuan Xue,Kaidi Luo,Yu Liu,Jing Lai,Xiuxiu Yao,Yunxia Xue,Wendi Huo,Cong Meng,Dongfang Xia,Xueyun Gao,Qing Yuan,Kai Cao
出处
期刊:ACS Nano
[American Chemical Society]
日期:2023-09-10
卷期号:17 (18): 18421-18432
被引量:7
标识
DOI:10.1021/acsnano.3c06025
摘要
Inflammatory bowel disease (IBD) is one of the main factors leading to colitis-associated colorectal cancer (CAC). Therefore, it is critical to develop an effective treatment for IBD to prevent secondary colorectal carcinogenesis. M2 macrophages play crucial roles in the resolution phase of intestinal inflammation. However, traditional drugs rarely target intestinal M2 macrophages, and they are not easily cleared. Gold nanoclusters are known for their in vivo safety and intrinsic biomedical activities. In this study, a glutathione-protected gold nanocluster is synthesized and evaluated, namely, GA. Interestingly, GA specifically accumulates in the colon during IBD. Furthermore, GA not only promotes M2 differentiation of IL-4-treated peritoneal macrophages but also reprograms macrophage polarization from M1 to M2 in a pro-inflammatory environment. Mechanistically, this regulatory effect is exerted through activating the antioxidant Nrf2 signaling pathway, but not traditional STAT6. When applied in IBD mice, we found that GA elevates M2 macrophages and alleviates IBD in an Nrf2-dependent manner, evidenced by the abolished therapeutic effect upon Nrf2 inhibitor treatment. Most importantly, GA administration significantly suppresses AOM/DSS-induced CAC, without causing obvious tissue damage, providing critical evidence for the potential application of gold nanoclusters as nanomedicine for the treatment of IBD and CAC.
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