工程化细菌外囊泡的构建策略与诊疗应用

Engineered bacterial extracellular vesicles: construction strategies and theranostic applications

摘要

细菌外囊泡(bacterial Extracellular Vesicles,bEVs)是细菌分泌的天然纳米膜囊泡,具备来源广泛、稳定性佳、生物相容性优异及可工程化改造等固有优势,是生物医学领域极具潜力的天然纳米平台。为实现bEVs的功能定制与临床转化,研究人员开发了多维度工程化构建策略,通过内在基因工程、表面修饰及载药包封等手段,实现了bEVs靶向性、载药效率、免疫调控能力的精准优化。近年来,工程化bEVs的诊疗应用潜力被深度挖掘:作为新型诊断标志物,其丰度与内容物可灵敏反映机体病理生理状态,为疾病无创早期诊断提供新途径;作为创新疫苗载体,可高效递送抗原并激活强效免疫应答,成为耐药菌感染防控的重要方向;作为靶向治疗工具,经工程化改造后可实现治疗分子的精准递送,在肿瘤、组织修复、抗感染等疾病中展现出协同治疗效果。本文系统阐述bEVs的基础生物学特性,重点梳理工程化bEVs的核心构建策略,全面总结其在疾病诊断、疫苗开发及靶向治疗中的最新研究进展,评述当前研究热点与关键问题,并探讨领域面临的挑战及未来发展方向,以期为工程化bEVs的临床转化及新型诊疗平台开发提供理论依据与实践策略。

Abstract

Bacterial Extracellular Vesicles (bEVs) are natural nanoscale membrane vesicles secreted by bacteria, which possess inherent advantages such as diverse sources, high stability, favorable biocompatibility and amenability to engineering, making them a promising natural bio-nano platform in the biomedical field. To achieve functional customization and clinical translation of bEVs, researchers have developed multi-dimensional engineering construction strategies. Through intrinsic genetic engineering, surface modification and drug loading encapsulation, the targeting ability, drug loading efficiency and immune regulation capacity of bEVs have been precisely optimized. In recent years, the diagnostic and therapeutic potential of engineered bEVs has been deeply explored: as novel diagnostic biomarkers, their abundance and cargo can sensitively reflect the pathophysiological state of the organism, providing a new approach for non-invasive early diagnosis of diseases; as innovative vaccine vectors, they can efficiently deliver antigens and elicit robust immune responses, becoming an important direction for the prevention and control of drug-resistant bacterial infections; as targeted therapeutic tools, they can achieve precise delivery of therapeutic molecules after engineering modification, showing synergistic therapeutic effects in tumors, tissue repair, anti-infection and other diseases. This article systematically elaborates on the basic biological characteristics of bEVs, focuses on sorting out the core construction strategies of engineered bEVs, comprehensively summarizes the latest research progress of engineered bEVs in disease diagnosis, vaccine development and targeted therapy, reviews the current research hotspots and key issues, and discusses the challenges and future development directions in the field, aiming to provide theoretical basis and practical strategies for the clinical translation of engineered bEVs and the development of novel diagnostic and therapeutic platforms.

关键词

细菌外囊泡 / 工程化构建策略 / 靶向递送 / 载药包封 / 诊疗应用 / 疫苗载体 / 疾病诊断

Key words

Bacterial extracellular vesicles / Engineered construction strategies / Targeted delivery / Drug loading encapsulation / Thoranostic applications / Vaccine vectors / Disease diagnosis

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