Ma Ning, Cai Kun, Zhao Jingwen, Liu Chunchen, Li Huahui, Tan Peng, Li Yuan, Li Defa, Ma Xi
State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Disease, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China.
Adv Mater. 2025 Aug;37(32):e2503056. doi: 10.1002/adma.202503056. Epub 2025 Apr 25.
Pathogenic bacterial infections pose a major concern, especially concerning mammalian enteritis and diarrhea. Compared to conventional antibiotic intervention, metal-organic frameworks (MOFs) exhibit superior antibacterial properties and lower cytotoxicity, demonstrating great promise in the treatment of pathogen-induced diarrhea. However, the achievement of their precise targeted delivery is still a significant challenge. Herein, a novel precision nano-system with a dual-targeting approach for treating intestinal infections caused by Escherichia coli (E. coli) is designed. First, Zn-MOF was synthesized based on ZnO, which possessed enhanced elimination of planktonic bacteria and biofilms. Through mannosylation, Zn-MOF@Man specifically recognized the FimH pili of E. coli, leading to its aggregation and subsequent eradication. Second, guided by whole genome sequencing, the encapsulation of Lactobacillus biofilm exertd immunomodulatory function, overcomed challenges related to intestinal targeting, and facilitated sustained drug release. Furthermore, Zn-MOF@Man/LRB maintaind microbiota equilibrium and promoted stem cell differentiation and barrier stability, ensuring consistent anti-diarrheal and anti-inflammatory efficacy in mice, piglets, and humans. This approach represents a novel dual-targeting antimicrobial strategy, combining probiotic biofilms and E. coli-oriented delivery, advancing safe and effective treatment that restores intestinal homeostasis for potential applications in both human medicine and animal husbandry.
致病性细菌感染是一个主要问题，尤其是在哺乳动物肠炎和腹泻方面。与传统抗生素干预相比，金属有机框架（MOFs）具有卓越的抗菌性能和较低的细胞毒性，在治疗病原体引起的腹泻方面显示出巨大潜力。然而，实现其精确靶向递送仍然是一项重大挑战。在此，设计了一种用于治疗由大肠杆菌（E. coli）引起的肠道感染的具有双重靶向方法的新型精确纳米系统。首先，基于ZnO合成了Zn-MOF，其对浮游细菌和生物膜的清除能力增强。通过甘露糖化，Zn-MOF@Man特异性识别大肠杆菌的FimH菌毛，导致其聚集并随后被根除。其次，在全基因组测序的指导下，乳酸杆菌生物膜的包封发挥了免疫调节功能，克服了与肠道靶向相关的挑战，并促进了药物的持续释放。此外，Zn-MOF@Man/LRB维持了微生物群平衡，促进了干细胞分化和屏障稳定性，确保在小鼠、仔猪和人类中具有一致的止泻和抗炎功效。这种方法代表了一种新型的双重靶向抗菌策略，将益生菌生物膜和以大肠杆菌为导向的递送相结合，推进了安全有效的治疗，恢复肠道内环境稳定，有望在人类医学和畜牧业中得到应用。
