Rapid drug clearance and off-target effects of therapeutic drugs can induce low bioavailability and systemic side effects and gravely restrict the therapeutic effects of inflammatory bowel diseases (IBDs). Here, we propose an amplifying targeting strategy based on orally administered gallium (Ga)-based liquid metal (LM) nano-agents to efficiently eliminate reactive oxygen and nitrogen species (RONS) and modulate the dysregulated microbiome for remission of IBDs. Taking advantage of the favorable adhesive activity and coordination ability of polyphenol structure, epigallocatechin gallate (EGCG) is applied to encapsulate LM to construct the formulations (LM-EGCG). After adhering to the inflamed tissue, EGCG not only eliminates RONS but also captures the dissociated Ga to form EGCG-Ga complexes for enhancive accumulation. The detained composites protect the intestinal barrier and modulate gut microbiota for restoring the disordered enteral microenvironment, thereby relieving IBDs. Unexpectedly, LM-EGCG markedly decreases the Escherichia_Shigella populations while augmenting the abundance of Akkermansia and Bifidobacterium , resulting in favorable therapeutic effects against the dextran sulfate sodium-induced colitis.

中文翻译：

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口服液态金属制剂用于炎症靶向缓解炎症性肠病


治疗药物的快速药物清除和脱靶效应会导致生物利用度低和全身副作用，严重限制炎症性肠病（IBD）的治疗效果。在这里，我们提出了一种基于口服镓（Ga）基液态金属（LM）纳米制剂的放大靶向策略，以有效消除活性氧和氮物种（RONS）并调节失调的微生物组以缓解IBD。利用多酚结构良好的粘附活性和配位能力，将表没食子儿茶素没食子酸酯（EGCG）封装到LM中构建制剂（LM-EGCG）。 EGCG粘附到发炎组织后，不仅可以消除RONS，还可以捕获解离的Ga，形成EGCG-Ga复合物，从而增强积累。所捕获的复合材料可以保护肠道屏障并调节肠道微生物群，以恢复紊乱的肠道微环境，从而缓解炎症性肠病。出乎意料的是，LM-EGCG 显着降低了大肠杆菌_志贺氏菌人口数量同时增加阿克曼氏菌和双歧杆菌，对葡聚糖硫酸钠诱发的结肠炎有良好的治疗效果。