Bioencapsulation of probiotics with self-assembled DNA capsules for the treatment of inflammatory bowel diseases

Intestinal probiotics play a critical role in the prevention and treatment of diseases and have been developed as a drug carrier in biomedical engineering. However, the application of probiotics for oral delivery is hindered by their poor viability in the harsh gastrointestinal tract (GIT) and their unsatisfactory-drug loading efficiency. Herein, we propose a universal and programmable strategy for coating bacteria with self-assembled deoxyribonucleic acid (DNA) capsules. We conducted in-situ DNA-oriented polymerization (isDOP) on bacteria and directly synthesized microcapsules on live bacterial cells using rolling circle amplification (RCA). Additionally, Fe-Curcumin (Fe-Cur), a reactive oxygen species (ROS)-scavenging nanodrug, was simultaneously enveloped in the DNA network during amplification. Bacteria coated with DNA capsules exhibit significantly enhanced survival in harsh environments. In murine colitis models, this system exhibited enhanced therapeutic efficacy by relieving intestinal inflammation and repairing the epithelial barrier with no apparent systemic toxicity. It also restores the gut microbiome to a favorable state of diversity and composition. We suggest that self-assembled DNA capsule improves the viability of oral delivery of probiotics and provides a platform for efficient drug loading, ensuring enhanced therapeutic effects for the treatment of various diseases. This study proposes a bacteria-based isDOP method, a flexible and simplified strategy for equipping probiotics with DNA that significantly enhances their loading capacity and viability, thereby ensuring enhanced therapeutic effects for the treatment of various diseases.