An antibiotic-free platform for eliminating persistent infection without disrupting gut microbiota.

( 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.