Single-cell probiotic encapsulation with a sandwich-structured nanocoating for intestinal-targeted delivery and inflammatory-responsive drug release.

Surface-engineered probiotics represent a promising therapeutic strategy for treating ulcerative colitis (UC). However, their therapeutic efficacy is often compromised by the complex pathological conditions and limited drug integration capacity. To overcome these therapeutic challenges, we developed a single-cell probiotic encapsulation system featuring with a sandwich-structured nanocoating (LGG@PLD-AS/ALG). The inner poly (L-dopa) (PLD) layer not only exhibited potent radical-scavenging capability, but also facilitated the dynamic loading of anti-inflammatory small molecule drugs (5-aminosalicylic acid, 5-ASA). Specifically, pathological reactive oxygen species (ROS) at the UC site triggered the cleavage of covalent bonds, resulting in on-demand 5-ASA release. Meanwhile, the outer alginate layer enabled intestinal-targeted delivery of probiotics and preventing premature 5-ASA leakage by undergoing pH-responsive degradation. In a dextran sulfate sodium (DSS)-induced murine colitis model, LGG@PLD-AS/ALG effectively promoted restoration of the intestinal barrier, rebalanced gut microbiota and alleviated colonic inflammation. This work proposes a novel single-cell probiotic encapsulation system with a sandwich-structured nanocoating, paving a new avenue for UC therapy.