Targeted and activatable nanosystem for fluorescent and optoacoustic imaging of immune-mediated inflammatory diseases and therapy via inhibiting NF-κB/NLRP3 pathways

Immune-mediated inflammatory diseases(IMIDs)represent a diverse group of diseases and challenges remain for the current medications.Herein,we present an activatable and targeted nanosystem for detecting and imaging IMIDs foci and treating them through blocking NF-κB/NLRP3 pathways.A ROS-activatable prodrug BH-EGCG is synthesized by coupling a near-infrared chromophore with the NF-κB/NLRP3 inhibitor epigallocatechin-3-gallate(EGCG)through boronate bond which serves as both the fluorescence quencher and ROS-responsive moiety.BH-EGCG molecules readily form stable nanoparticles in aqueous medium,which are then coated with macrophage membrane to ensure the actively-targeting capability toward inflammation sites.Additionally,an antioxidant precursor N-acetylcysteine is co-encapsulated into the coated nanoparticles to afford the nanosystem BH-EGCG&NAC@MM to further improve the anti-inflammatory efficacy.Benefiting from the inflammation-homing effect of the macrophage membrane,the nanosystem delivers payloads(diagnostic probe and therapeutic drugs)to inflammatory lesions more efficiently and releases a chromophore and two drugs upon being triggered by the overexpressed in-situ ROS,thus exhibiting better theranostic performance in the autoimmune hepatitis and hind paw edema mouse models,including more salient imaging signals and better therapeutic efficacy via inhibiting NF-κB pathway and suppressing NLRP3 inflammasome activation.This work may provide perceptions for designing other actively-targeting theranostic nanosystems for various inflammatory diseases.