Cucurbit[8]uril was employed as a supramolecular linker to assemble chitosan/hyaluronic acid multilayers on the periphery of a mesoporous silica core to provide a synergistic gut microbiota-targeting approach for IBD therapy.

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We show how the macrocyclic host cucurbit[8]­uril (CB[8]) and a fluorescent dye form a biosensing ensemble while its cavity simultaneously traps tryptophan, the upstream substrate of IDO1 enzymes, therefore providing a label-free method to monitor the activity of IDO1 in real time. Incubation of malignant HeLa and HepG2 cells overexpressing IDO1 with the associative biosensor resulted in its spontaneous uptake and a fluorescence switch-on response in situ, which can be traced to the displacement of tryptophan from CB[8] upon IDO1-catalyzed oxidation. The results, for the first time, establish a supramolecular sensing concept for the detection of intracellular enzymatic activity in live cells, thus allowing direct cell-based analysis and inhibitor screening compatible with commercial instruments including microplate reader, fluorescent microscopy, and flow cytometry.

Dual exonucleases to finely distinguish structural adjustment of aptamers to produce absolute differentiation between digestion and inhibition.