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

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 poly -phenol-armored nanomedicine based on tumor necrosis factor-alpha (TNF-alpha)-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-alpha- siRNA delivery. Unexpectedly, the armored nanomedicine suppressed hyperactive immune responses and mod-ulated bacterial gut microbiota homeostasis in a mouse model of acute colitis. Notably, the armored nanome-dicine 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.