Probiotic Membrane-Modified Nanocomposite Alleviates Inflammation and Microbiota Dysbiosis in Colitis by Scavenging Oxidative Stress and Restoring Immune Homeostasis

Inflammatory bowel disease (IBD) is a complex chronic intestinal disorder in which excessive oxidative stress, dysregulated immune response, and microbiota dysbiosis contribute to recurrent episodes of inflammation in the colonic mucosa. Current clinical treatments focusing solely on inflammation resolution often exhibit limited efficacy due to the inability to fundamentally improve the pathological microenvironment. Herein, a probiotic membrane-modified drug delivery nanocomposite, namely, MPDA@Cur@EM, is developed for the comprehensive treatment of IBD. It contains two components: the curcumin-loaded mesoporous polydopamine nanoparticle (MPDA@Cur) as the core and the <i>Escherichia coli</i> Nissle 1917 outer membrane (EM) as the surface. For MPDA@Cur, the pathological microenvironment triggers the responsive release of curcumin. Importantly, MPDA@Cur can effectively alleviate the inflammatory response of LPS-activated macrophages through MPDA-mediated ROS scavenging and curcumin-induced M2 polarization. In the dextran sulfate sodium (DSS)-induced colitis model, the EM coating not only allows for the targeting enrichment of orally administered MPDA@Cur@EM to the inflamed colonic mucosa, but also participates in the regulation of intestinal flora. Consequently, MPDA@Cur@EM efficiently attenuates the inflammatory reaction and restores the intestinal barrier functions, demonstrated by the multipronged manner of restoring redox balance, remodeling immune homeostasis, and reshaping the gut microecology. Collectively, this work provides a safe and promising codelivery strategy of probiotic product, antioxidative nanoenzyme, and therapeutic drug for comprehensive management of IBD.