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.

中文翻译：

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口服多酚装甲纳米药物用于靶向调节结肠炎肠道微生物群-大脑相互作用


开发抑制肠道炎症同时调节肠道微生物群和大脑相互作用的口服纳米药物对于有效治疗炎症性肠病至关重要。在这里，我们报道了一种基于肿瘤坏死因子-α（TNF-α）-小干扰RNA和没食子酸介导的石墨烯量子点（GAGQD）-封装牛血清白蛋白纳米颗粒，以及壳聚糖和单宁酸的口服多酚装甲纳米药物（CHI/TA）多层。 CHI/TA 多层被称为“盔甲”，可以抵抗胃肠道的恶劣环境，并有针对性地粘附在发炎的结肠部位。 TA 提供抗氧化应激和益生元活性，调节多样化的肠道微生物群。此外，GAGQD 保护 TNF-α-siRNA 的传递。出乎意料的是，装甲纳米药物在急性结肠炎小鼠模型中抑制了过度活跃的免疫反应并调节细菌肠道微生物群的稳态。值得注意的是，装甲纳米药物减轻了结肠炎小鼠的焦虑和抑郁样行为以及认知障碍。这种装甲策略揭示了口服纳米药物对细菌肠道微生物组与大脑相互作用的影响。