Progress and challenges of functionalized bacterial encapsulation: a novel biotechnology for next-generation biotherapeutics

Available online 23 July 2025

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The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.

Graphical abstractThis review summarizes functionalized encapsulation strategies based on covalent modification and self-assembly, which construct physical barriers and enhance material properties to improve the viability and targeted delivery capabilities of live therapeutic bacteria in harsh gastrointestinal environments, offering innovative pathways for next-generation microbial therapies.