Bacteria-based drug delivery for treating non-oncological diseases

Bacteria inhabit all over the human body, especially the skin, gastrointestinal tract, respiratory tract, urogenital tract, as well as specific lesion sites, such as wound and tumor. By leveraging their distinctive attributes including rapid proliferation, inherent abilities to colonize various biointerfaces in vivo and produce diverse biomolecules, and the flexibility to be functionalized via genetic engineering or surface modification, bacteria have been widely developed as living therapeutic agents, showing promising potential to make a great impact on the exploration of advanced drug delivery systems. In this review, we present an overview of bacteria-based drug delivery and its applications in treating non-oncological diseases. We systematically summarize the physiological positions where living bacterial therapeutic agents can be delivered to, including the skin, gastrointestinal tract, respiratory tract, and female genital tract. We discuss the success of using bacteria-based drug delivery systems in the treatment of diseases that occur in specific locations, such as skin wound healing/infection, inflammatory bowel disease, respiratory diseases, and vaginitis. We also discuss the advantages as well as the limitations of these living therapeutics and bacteria-based drug delivery, highlighting the key points that need to be considered for further translation. This review article may provide unique insights for designing next-generation bacteria-based therapeutics and developing advanced drug delivery systems.