Zou Zhen-Ping, Cai Zhihao, Zhang Xiao-Peng, Zhang Donghui, Xu Chu-Ying, Zhou Ying, Liu Runhui, Ye Bang-Ce
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Key Laboratory of Specially Functional Polymeric Materials and Related Technology (Ministry of Education), Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China.
Adv Healthc Mater. 2025 Jan;14(3):e2403704. doi: 10.1002/adhm.202403704. Epub 2024 Dec 4.
Engineered bacterial therapy holds enormous potential for treating intestinal diseases, employing synthetic biology techniques to achieve localized drug delivery within intestines. However, effective delivery of engineered bacteria to lesion sites and ensuring sustained colonization remain challenging. Here, a mucus encapsulated microsphere gel (MM) delivery system is developed to encapsulate genetically engineered bacteria capable of detecting and treating enteritis. The MM delivery system features an external mucosal coating composed of hyaluronic acid and epigallocatechin gallate, along with internal microspheres of highly biocompatible polyserine modified alginates encapsulating with the engineered probiotics. The MM delivery system effectively protects engineered bacteria harsh environment in stomach and significantly improves intestinal adhesion of the probiotics, extending colonization up to 24 h, and does not affect the entry of biomarker or release of Avcystatin. It exhibits notable diagnostic and therapeutic efficacy in inflammatory bowel disease models, thus facilitating the advancement of live biotherapeutic products toward clinical application.
工程细菌疗法在治疗肠道疾病方面具有巨大潜力，它利用合成生物学技术在肠道内实现局部药物递送。然而，将工程细菌有效递送至病变部位并确保持续定植仍然具有挑战性。在此，开发了一种黏液包裹微球凝胶（MM）递送系统，用于封装能够检测和治疗肠炎的基因工程细菌。MM递送系统的特点是具有由透明质酸和表没食子儿茶素没食子酸酯组成的外部黏膜涂层，以及内部由高度生物相容性的聚丝氨酸修饰藻酸盐微球包裹工程益生菌。MM递送系统有效地保护工程细菌免受胃部恶劣环境的影响，并显著提高益生菌在肠道的黏附性，将定植时间延长至24小时，且不影响生物标志物的进入或阿伐斯汀的释放。它在炎症性肠病模型中表现出显著的诊断和治疗效果，从而推动活体生物治疗产品向临床应用发展。
