Chemotaxis-driven hybrid liposomes trilogically recover intestinal homeostasis for targeted therapy of ulcerative colitis

Ulcerative colitis (UC) is tightly linked to the dysbiosis of intestinal homeostasis, accompanied by the intestinal epithelial barrier destruction, subsequent inflammatory factor infiltration, and excessive oxidative stress. However, conventional therapeutics only focus on suppressing inflammation and often suffer from metabolic instability as well as limited targeting, thereby leading to suboptimal remission rates and severe side effects. Here, we initially fabricated bacterial outer membrane vesicle (OMV, from Stenotrophomonas maltophilia )-fused and borneol-modified liposomes (BO/OMV-lipo@LU) to deliver luteolin for targeted therapy of UC by recovering intestinal homeostasis. Benefitting from the chemotaxis-driven colon-targeting ability of OMVs and intestinal epithelial uptake promotion of borneol, the hybrid liposomes exhibited excellent targeting capability towards the inflamed colon. Moreover, under the combined effects of OMVs and borneol, interestingly, the hybrid liposomes achieved deep penetration into the mucosa for better uptake of luteolin by the intestinal epithelium. Notably, BO/OMV-lipo@LU with favorable biosafety exerted promising therapeutic efficacy and trilogically recovered intestinal homeostasis in UC by alleviating intestinal inflammation, modulating redox balance, and restoring intestinal epithelial barriers. These results demonstrated that such a biomimetic nanoplatform could be exploited as a safe and effective gut-targeted delivery system for UC intervention.