Surface-functionalized bacteria: Frontier explorations in next-generation live biotherapeutics

Screening robust living bacteria to produce living biotherapeutic products (LBPs) represents a burgeoning research field in biomedical applications. Despite their natural abilities to colonize bio-interfaces and proliferate, harnessing bacteria for such applications is hindered by considerable challenges in unsatisfied functionalities and safety concerns. Leveraging the high degree of customization and adaptability on the surface of bacteria demonstrates significant potential to improve therapeutic outcomes and achieve tailored functionalities of LBPs. This review focuses on the recent laboratory strategies of bacterial surface functionalization, which aims to address these challenges and potentiate the therapeutic effects in biomedicine. Firstly, we introduce various functional materials that are used for bacterial surface functionalization involving organic, inorganic, and biological materials. Secondly, the methodologies for achieving bacterial surface functionalization are categorized into three primary approaches including covalent bonding, non-covalent interactions, and hybrid techniques, while various advantages and limitations of different modification strategies are compared from multiple perspectives. Subsequently, the current status of the applications of surface-functionalized bacteria in bioimaging and disease treatments, especially in the treatment of inflammatory bowel disease (IBD) and cancer is summarized. Finally, challenges and pressing issues in the development of surface-functionalized bacteria as LBPs are presented.