Oral Nanoarmored Lactobacillus rhamnosus with Inflammation Targeting and Scavenging Activities for Colitis Lesion-Specific Therapy

Abstract

Abstract Nanoarmored probiotics with inflammation targeting and scavenging activities without complex synthetic procedure is important for maintaining their native bioactivity, yet it remains a challenge. In this work, we demonstrated the multifunctional nanoparticle (QL@PS NP)-armored Lactobacillus rhamnosus (LAB) with inflammation targeting and regulation activity for inflammatory bowel disease (IBD) treatment. QL@PS NPs were assembled by quercetin (Que), lipoic acid (LA), and phosphatidylserine (PS), which could target macrophages and degrade in reactive oxygen species (ROS)-rich lesion sites, exhibiting excellent antioxidant and anti-inflammatory capability in vitro. QL@PS NPs were coated on the surface of thiolated LAB under a cell-friendly condition, and the resulting nanoarmored probiotic (LAB@NPs) could protect LAB from the gastrointestinal assaults and ROS damage. LAB@NPs are more likely to be up-taken by macrophages, scavenging oxidative stress and regulating the inflammatory microenvironment of colitis lesions through the synergistic effect of probiotics and QL@PS NPs. In vivo experimental results certified that LAB@NPs achieved notable lesion-specific therapeutic efficacy in mouse colitis models, significantly ameliorating colon shortening, reducing inflammatory reactions and pathological tissue damage. This work provides a facile and effective strategy to construct nanoarmored probiotics for therapy of IBD.