Metal ion-based inhibition of urease activity is a promising strategy for treating Helicobacter pylori (H. pylori) infections. However, the challenges of safe delivery and reducing cytotoxicity persist. In this study, an innovative nanocarrier capable of acid-responsive release of Ag⁺ and antibiotics is developed, with complete degradation after treatment. Mesoporous organosilica nanoparticle (MON) is encapsulated with hyaluronic acid (HA) to prevent drug leakage and further coated with bacterial outer membrane vesicle (OMV) from Escherichia coli Nissle 1917, creating a nanocarrier with cell-protective capabilities. Ag⁺ and antibiotic clarithromycin (CLR) are incorporated into the nanocarrier to form CLR-Ag⁺@MON@HA@OMV (CAMO), designed for the targeted treatment of gastric H. pylori infection. The HA encapsulation ensures acid-responsive release of CLR and Ag⁺ in the stomach, preventing premature release at non-inflammatory sites. There is a potential for Ag⁺ in CAMO to replace Ni²⁺ at the active site of urease, enhancing the bactericidal effect of CLR through urease inhibition. Furthermore, the OMV provides additional cytoprotection, mitigating cell damage and inflammation response induced by the H. pylori infection. This study introduces a safe and effective nanocarrier that eradicates H. pylori and alleviates gastric inflammation.

中文翻译：

---

可生物降解的酸响应性纳米载体，通过脲酶抑制增强对耐药幽门螺杆菌的抗生素治疗


基于金属离子的脲酶活性抑制是治疗幽门螺杆菌 （H. pylori） 感染的一种有前途的策略。然而，安全递送和降低细胞毒性的挑战仍然存在。在本研究中，开发了一种能够酸响应性释放 Ag⁺ 和抗生素的创新纳米载体，处理后完全降解。介孔有机硅纳米颗粒 （MON） 用透明质酸 （HA） 封装以防止药物泄漏，并进一步涂覆来自大肠杆菌 Nissle 1917 的细菌外膜囊泡 （OMV），从而产生具有细胞保护能力的纳米载体。Ag⁺ 和抗生素克拉霉素 （CLR） 被掺入纳米载体中形成 CLR-Ag⁺@MON@HA@OMV （CAMO），设计用于靶向治疗胃幽门螺杆菌感染。HA 封装确保 CLR 和 Ag⁺ 在胃中酸反应性释放，防止在非炎症部位过早释放。CAMO 中的 Ag⁺ 有可能取代脲酶活性位点的 Ni²⁺，通过抑制脲酶增强 CLR 的杀菌作用。此外，OMV 提供额外的细胞保护，减轻幽门螺杆菌感染诱导的细胞损伤和炎症反应。本研究介绍了一种安全有效的纳米载体，可以根除幽门螺杆菌并缓解胃炎。