An AIEgen-based oral-administration nanosystem for detection and therapy of ulcerative colitis via 3D-MSOT/NIR-II fluorescent imaging and inhibiting NLRP3 inflammasome.

Ulcerative colitis is the most prevalent forms of inflammatory bowel diseases and a refractory autoimmune disease and affects millions of people worldwide. Herein, we develop an oral-administration nanosystem (QM@EP) for colitis detection, targeted drug delivery/release to colon and therapy. QM@EP consists of a molecular probe QY-SN-H2O2, a NLRP3 inhibitor MCC950 and enteric polymers. QY-SN-H2O2 is based on the AIE-active chromophore QY-SN-OH with pentafluorobenzenesulfonate moieties as the recognition moiety for the biomarker H2O2 and the fluorescence quencher. H2O2 can cleave the pentafluorobenzenesulfonate moieties in QY-SN-H2O2 and thus generating the AIE-active chromophore Q-SN-OH. Two biocompatible polymers were employed in the nanosystem, in which poly(lactic-co-glycolic acid) (PLGA) serves as the sustained release excipient and the Eudragit® S100 acts as the excipient for controlled release of drug formulations in colonic pH to prevent premature drug release in stomach. Our experiments demonstrate that, upon oral administration the nanosystem effectively delivers the probe and drug into colon and release them therein upon being triggered by colonic pH. Then the released probe is activated and turned into the AIE-active chromophore upon being triggered by the pathological level of colonic ROS, thereby bringing about strong fluorescence and optoacoustic signals for NIR-II fluorescence and 3D multispectral optoacoustic tomography (MSOT) imaging for diagnosis and therapeutic outcome monitoring; and the released drug exerts high therapeutic efficacy against ulcerative colitis through inhibiting NLRP3 inflammasome formation.