The human body is a natural habitat for a multitude of microorganisms, with bacteria being the major constituent of the microbiota. These bacteria colonize discrete anatomical locations that provide suitable conditions for their survival. Many bacterial species, both symbiotic and pathogenic, interact with the host via biochemical signaling. Based on these attributes, commensal and attenuated pathogenic bacteria have been engineered to deliver therapeutic molecules to target specific diseases. Recent advances in synthetic biology have enabled us to perform complex genetic modifications in live bacteria and bacteria-derived particles, which simulate micron or submicron lipid-based vectors, for the targeted delivery of therapeutic agents. In this review, we highlight various examples of engineered bacteria or bacteria-derived particles that encapsulate, secrete, or surface-display therapeutic molecules for the treatment or prevention of various diseases. The review highlights recent studies on (i) the production of therapeutics by microbial cell factories, (ii) disease-triggered release of therapeutics by sense and respond systems, (iii) bacteria targeting tumor hypoxia, and (iv) bacteria-derived particles as chassis for drug delivery. In addition, we discuss the potential of such drug delivery systems to be translated into clinical therapies.

人体是众多微生物的自然栖息地，其中细菌是微生物群的主要组成部分。这些细菌在离散的解剖位置定殖，为它们的生存提供合适的条件。许多细菌物种，无论是共生的还是致病的，都通过生化信号与宿主相互作用。基于这些属性，共生和减毒病原菌已被设计用于递送治疗分子以靶向特定疾病。合成生物学的最新进展使我们能够在活细菌和细菌衍生颗粒中进行复杂的遗传修饰，这些颗粒模拟微米或亚微米脂质载体，用于靶向递送治疗剂。在这篇评论中，我们重点介绍了用于治疗或预防各种疾病的工程化细菌或细菌衍生颗粒的各种示例，它们封装、分泌或表面展示治疗分子。该综述重点介绍了最近关于 (i) 微生物细胞工厂生产治疗剂，(ii) 通过感觉和反应系统释放治疗剂的疾病，(iii) 靶向肿瘤缺氧的细菌，以及 (iv) 细菌衍生颗粒作为用于药物输送的底盘。此外，我们讨论了这种药物输送系统转化为临床治疗的潜力。(ii) 通过感知和响应系统释放疾病触发的治疗剂，(iii) 靶向肿瘤缺氧的细菌，以及 (iv) 细菌衍生颗粒作为药物输送的底盘。此外，我们讨论了这种药物输送系统转化为临床治疗的潜力。(ii) 通过感知和响应系统释放疾病触发的治疗剂，(iii) 靶向肿瘤缺氧的细菌，以及 (iv) 细菌衍生颗粒作为药物输送的底盘。此外，我们讨论了这种药物输送系统转化为临床治疗的潜力。