Sub-micrometer/nanoscale patterned polymer brushes are prepared by employing cucurbit[8]uril (CB[8]) as a supramolecular recognition motif to assemble functional silica colloids onto Au surfaces as a sacrificial nanopatterning template. By employing CB[8]-mediated host–guest interactions at the interface, it is possible to readily generate nanopatterned materials in aqueous media under ambient conditions.

The fabrication, characterisation and controlled cargo release of hollow mesoporous raspberry-like colloids (HMRCs), which are assembled by utilising host–guest complexation of cucurbit[8]uril (CB[8]) are described.

Rationale: Inflammatory bowel diseases (IBDs) are still awaiting innovative treatments that can maximize the efficiency of site-specific drug release in the colon while enhancing intestinal homeostasis. Methods: Herein, we present multilayer-coated mesoporous silica (MSs) which release payload drugs specifically in the colon tract in the presence of azoreductase produced by the gut microbiota, and simultaneously rejuvenate the tryptophan metabolism of the microbiome to induce activation of the aryl hydrocarbon receptor (AHR) for increased anti-inflammatory effects. The MSs were prepared by using cucurbit[8]uril (CB[8]) as a supramolecular “handcuff” to assemble chitosan/hyaluronic acid multilayers on the periphery of a mesoporous silica core. Results: Strikingly, although MSs remained fairly stable in both acidic and neutral pH, they exhibited excellent responsiveness towards dithionite, an azo-reducing agent employed as a substitute to mimic the specific azoreductase environment in vitro. In comparison with the drug in its free form, hydrocortisone-loaded MSs showed optimized accumulation of therapeutics in the colonic mucosa with minimized premature release in the upper gastrointestinal tract in in vivo imaging and biodistribution studies. The enhanced therapeutic effects of MSs were confirmed in dextran sodium sulfate-induced colitis in mice with promoted colonic epithelial barrier integrity, elevated level of AHR agonists and modulated production of inflammatory cytokines. Furthermore, 16S rRNA analysis showed that the disrupted gut homeostasis of colitic mice was partly corrected by MSs. Conclusion: This novel drug delivery system using self-assembly of tryptophan-functionalized chitosan, which was precomplexed with CB[8], and azobenzene-functionalized hyaluronic acid on the surface of mesoporous silica nanoparticles provides a synergistic gut microbiota-targeting approach for IBD therapy.