( infection remains the leading cause of gastric adenocarcinoma, and its eradication primarily relies on the prolonged and intensive use of two antibiotics. However, antibiotic resistance has become a compelling health issue, leading to eradication treatment failure worldwide. Additionally, the powerlessness of antibiotics against biofilms, as well as intracellular and the long-term damage of antibiotics to the intestinal microbiota, have also created an urgent demand for antibiotic-free approaches. Herein, we describe an antibiotic-free, multifunctional copper-organic framework (HKUST-1) platform encased in a lipid layer comprising phosphatidic acid (PA), rhamnolipid (RHL), and cholesterol (CHOL), enveloped in chitosan (CS), and loaded in an ascorbyl palmitate (AP) hydrogel: AP@CS@Lip@HKUST-1. This platform targets inflammatory sites where aggregates through electrostatic attraction. Then, hydrolysis by matrix metalloproteinases (MMPs) releases CS-encased nanoparticles, disrupting bacterial urease activity and membrane integrity. Additionally, RHL disperses biofilms, while PA promotes lysosomal acidification and activates host autophagy, enabling clearance of intracellular . Furthermore, AP@CS@Lip@HKUST-1 alleviates inflammation and enhances mucosal repair through delayed Cu release while preserving the intestinal microbiota. Collectively, this platform presents an advanced therapeutic strategy for eradicating persistent infection without inducing drug resistance.

中文翻译：

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一个不含抗生素的平台，可在不破坏肠道微生物群的情况下消除持续的幽门螺杆菌感染

（感染仍然是胃腺癌的主要原因，其根除主要依靠两种抗生素的长期、大量使用。然而，抗生素耐药性已成为一个引人注目的健康问题，导致全球根除治疗失败。此外，抗生素对治疗胃腺癌无能为力。生物膜，以及抗生素对肠道微生物群的细胞内和长期损害，也产生了对无抗生素方法的迫切需求。在此，我们描述了一种无抗生素的多功能铜有机框架（HKUST-1）平台包裹在由磷脂酸（PA）、鼠李糖脂（RHL）和胆固醇（CHOL）组成的脂质层中，包裹在壳聚糖（CS）中，并负载在抗坏血酸棕榈酸酯（AP）水凝胶中：AP@CS@Lip@HKUST- 1. 该平台针对通过静电吸引聚集的炎症部位。然后，基质金属蛋白酶 (MMP) 水解，释放 CS 包裹的纳米颗粒，破坏细菌脲酶活性和膜完整性。此外，RHL 分散生物膜，而 PA 促进溶酶体酸化并激活宿主自噬，从而能够清除细胞内的 。此外，AP@CS@Lip@HKUST-1 通过延迟铜释放来减轻炎症并增强粘膜修复，同时保护肠道微生物群。总的来说，该平台提出了一种先进的治疗策略，可以在不诱导耐药性的情况下根除持续感染。