Oral polyphenol-armored nanomedicine for targeted modulation of gut microbiota–brain interactions in colitis

作者：Huan He, Qiaozhen Qin, Fang Xu, Yitong Chen, Shuquan Rao, Chao Wang, Xiaoxia Jiang, Xiong Gang Lu, Chaoming Xie · 发表于：Science Advances · 年份：2023 · DOI：10.1126/sciadv.adf3887 · 被引用次数：152 · 研究领域：Gut microbiota and health、Infant Nutrition and Health、Probiotics and Fermented Foods

Developing oral nanomedicines that suppress intestinal inflammation while modulating gut microbiota and brain interactions is essential for effectively treating inflammatory bowel disease. Here, we report an oral polyphenol-armored nanomedicine based on tumor necrosis factor-α (TNF-α)-small interfering RNA and gallic acid-mediated graphene quantum dot (GAGQD)-encapsulated bovine serum albumin nanoparticle, with a chitosan and tannin acid (CHI/TA) multilayer. Referred to "armor," the CHI/TA multilayer resists the harsh environment of the gastrointestinal tract and adheres to inflamed colon sites in a targeted manner. TA provides antioxidative stress and prebiotic activities that modulate the diverse gut microbiota. Moreover, GAGQD protected TNF-α-siRNA delivery. Unexpectedly, the armored nanomedicine suppressed hyperactive immune responses and modulated bacterial gut microbiota homeostasis in a mouse model of acute colitis. Notably, the armored nanomedicine alleviated anxiety- and depression-like behaviors and cognitive impairment in mice with colitis. This armor strategy sheds light on the effect of oral nanomedicines on bacterial gut microbiome-brain interactions.