Responsively Degradable Nanoarmor‐Assisted Super Resistance and Stable Colonization of Probiotics for Enhanced Inflammation‐Targeted Delivery

Manipulation of the gut microbiota using oral microecological preparations has shown great promise in treating various inflammatory disorders. However, delivering these preparations while maintaining their disease‐site specificity, stability, and therapeutic efficacy is highly challenging due to the dynamic changes associated with pathological microenvironments in the gastrointestinal tract. Herein, a superior armored probiotic with an inflammation‐targeting capacity is developed to enhance the efficacy and timely action of bacterial therapy against inflammatory bowel disease (IBD). The coating strategy exhibits suitability for diverse probiotic strains and has negligible influence on bacterial viability. This study demonstrates that these armored probiotics have ultraresistance to extreme intraluminal conditions and stable mucoadhesive capacity. Notably, the HA‐functionalized nanoarmor equips the probiotics with inflamed‐site targetability through multiple interactions, thus enhancing their efficacy in IBD therapy. Moreover, timely “awakening” of ingested probiotics through the responsive transferrin‐directed degradation of the nanoarmor at the site of inflammation is highly beneficial for bacterial therapy, which requires the bacterial cells to be fully functional. Given its easy preparation and favorable biocompatibility, the developed single‐cell coating approach provides an effective strategy for the advanced delivery of probiotics for biomedical applications at the cellular level. A superior armored probiotic (EcN@PC–Fe/HA) with an inflammation‐targeting capacity is developed to enhance the efficacy and timely action of bacterial therapy against inflammatory bowel disease. EcN@PC–Fe/HA shows excellent prophylactic efficacy and therapeutic performance against dextran sulfate sodium‐induced colitis including alleviating inflammation, restoring intestinal barrier function, and reshaping the dysbiosis of intestinal bacteria.