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基于金属有机骨架的氢气释放平台用于多效靶向治疗幽门螺杆菌和保护肠道菌群的能力。

Metal-Organic-Framework-Based Hydrogen-Release Platform for Multieffective Helicobacter Pylori Targeting Therapy and Intestinal Flora Protective Capabilities.

机构信息

College of Chemistry of Nanchang University, Nanchang University, Nanchang, 330088, China.

Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, 330088, China.

出版信息

Adv Mater. 2022 Jan;34(2):e2105738. doi: 10.1002/adma.202105738. Epub 2021 Nov 14.

DOI:10.1002/adma.202105738
PMID:34655499
Abstract

Helicobacter pylori (H. pylori) infection is the leading cause of chronic gastritis, peptic ulcer, and gastric cancer. Antibiotics, as traditional method for eliminating H. pylori, have no targeting effect, which causes serious bacterial resistance and gut dysbacteriosis. Moreover, antibiotics can hardly address hyperactive inflammatory response or damaged gastric mucosal barrier caused by H. pylori infection. Here, a pH-responsive metal-organic framework hydrogen-generation nanoparticle (Pd(H) @ ZIF-8) is reported, which is encapsulated with ascorbate palmitate (AP) hydrogel. Both in vitro and in vivo experiments demonstrate that the outer AP hydrogel can target and adhere to the inflammatory site through electrostatic interactions, and is then hydrolyzed by matrix metalloproteinase (MMP) enriching in inflammatory sites. The released Pd(H) @ ZIF-8 nanoparticles are further decomposed by gastric acid to generate zinc ions (Zn ) and hydrogen, thus effectively killing H. pylori, alleviating inflammation and restoring impaired gastric mucosa simultaneously. Unexpectedly, this metal-organic framework hydrogen-generation platform (Pd(H) @ ZIF-8 @ AP) also has an effect toward avoiding the imbalance of intestinal flora, which thus provides a more precise, effective, and healthy strategy for the treatment of H. pylori infection.

摘要

幽门螺杆菌(H. pylori)感染是导致慢性胃炎、消化性溃疡和胃癌的主要原因。抗生素作为消除 H. pylori 的传统方法,没有靶向作用,这导致了严重的细菌耐药性和肠道菌群失调。此外,抗生素几乎无法解决 H. pylori 感染引起的过度活跃的炎症反应或受损的胃黏膜屏障。在这里,我们报道了一种 pH 响应型金属有机框架产氢纳米粒子(Pd(H)@ZIF-8),其被包裹在抗坏血酸棕榈酸酯(AP)水凝胶中。体外和体内实验均表明,外水凝胶通过静电相互作用靶向并黏附在炎症部位,然后被富含在炎症部位的基质金属蛋白酶(MMP)水解。释放的 Pd(H)@ZIF-8 纳米粒子进一步被胃酸分解生成锌离子(Zn )和氢气,从而有效杀灭 H. pylori,同时缓解炎症和修复受损的胃黏膜。出乎意料的是,这种金属有机框架产氢平台(Pd(H)@ZIF-8@AP)还可以避免肠道菌群失衡,为 H. pylori 感染的治疗提供了更精确、更有效、更健康的策略。

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