PDF(Pubmed)
Abstract：
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.
摘要：
治疗药物的快速药物清除和脱靶效应可导致低生物利用度和全身性副作用，并严重限制炎症性肠病（IBD）的治疗效果。这里,我们提出了一种基于口服镓（Ga）基液态金属（LM）纳米药物的扩增靶向策略，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合活性和配位能力，表没食子儿茶素没食子酸酯(EGCG)用于包封LM以构建制剂(LM-EGCG)。粘附到发炎的组织后，EGCG不仅消除了RONS，而且还捕获了解离的Ga以形成EGCG-Ga复合物以进行增强积累。滞留的复合材料保护肠道屏障和调节肠道微生物群，以恢复无序的肠内微环境，从而缓解IBD。出乎意料的是,LM-EGCG显着减少了大肠杆菌_志贺氏菌种群，同时增加了Akkermansia和双歧杆菌的丰度，对葡聚糖硫酸钠诱导的结肠炎产生良好的治疗效果。
