A multifunctional nanoaggregate‐based system for detection of rheumatoid arthritis via Optoacoustic/NIR‐II fluorescent imaging and therapy via inhibiting JAK‐STAT/NF‐κB/NLRP3 pathways

Abstract

Rheumatoid arthritis (RA) is a debilitating autoimmune disease that causes chronic pain and serious complications, presenting a significant challenge to treat. Promising approaches for treating RA involve signaling pathways modulation and targeted therapy. To this end, a multifunctional nanosystem, TPC‐U@HAT, has been designed for RA therapy, featuring multitargeting, dual‐stimuli response, and on‐demand drug release capabilities. TPC‐U@HAT is composed of a probe/prodrug TPC, a JAK1 kinase inhibitor upadacitinib, and the drug carrier HAT. TPC is composed of an aggregation‐induced emission (AIE)‐active NIR‐II chromophore TPY and an NF‐κB/NLRP3 inhibitor caffeic acid phenethyl ester (CAPE), connected via boronic ester bond which serves as the reactive‐oxygen‐species‐responsive linker. The carrier, HAT, is created by grafting bone‐targeting alendronate and hydrophobic tocopheryl succinate onto hyaluronic acid chains, which can encapsulate TPC and upadacitinib to form TPC‐U@HAT. Upon intravenous injection into mice, TPC‐U@HAT accumulates at inflamed lesions of RA through both active and passive targeting, and the overexpressed hyaluronidase and H2O2 therein cleave the hyaluronic acid polymer chains and boronate bonds, respectively. This generates an AIE‐active chromophore for detection and therapeutic evaluation of RA via both optoacoustic imaging and NIR‐II fluorescent imaging and concomitantly releases CAPE and upadacitinib to exert efficacious therapy by inhibiting NF‐κB/NLRP3 and JAK‐STAT pathways.

Near-infrared imaging for visualizing the synergistic relationship between autophagy and NFS1 protein during multidrug resistance using an ICT–TICT integrated platform

“…The response mechanism is provided in Scheme 1c and d. Vis-H 2 S , with a molecular rotor structure (two symmetric vinyl-coupled indolium moieties), enhanced the probe fluorescence in a high-viscosity environment due to restricted intramolecular rotation inhibiting nonradiative twisted intramolecular charge transfer (TICT 14–16 ). The nucleophilic reaction of the ester with HS − releases QCy7 in an anionic form, and the negative charge is delocalized to form quinone QCy7-a or QCy7-b .…”

Engineering Near-Infrared Fluorescent Probes Based on Modulation of Molecular Excited States

“…Aggregation-induced emission (AIE) concept, which was pioneered by the work of Tang and co-workers, has ushered new frontiers in biosensing and imaging. − Specifically, the AIE strategy is a valuable approach for tracking protein aggregates, organelles, and enzymes. , In aggregation-induced emission luminogens (AIEgens), the restriction of excited state intramolecular motion in the aggregated state effectively suppresses nonradiative decay, leading to enhanced fluorescence emission. In 2013, our group first reported that replacing the oxygen atom in dicyanomethylene-4 H -pyran (DCM) chromophore (a classical laser dye) with an N -ethyl group, and the obtaining quinoline-malononitrile (QM) exhibited a twisted molecular conformation with typical AIE properties .…”

An Asymmetric NIR-II Organic Fluorophore with an Ultra-Large Stokes Shift for Imaging-Guided and Targeted Phototherapy

“…24 In general, the strategies of structuring organic fluorophores with NIR-II emission consist of expanding π-systems, strengthening structural rigidity, and introducing strong donor and acceptor groups. 23 To date, various organic fluorescence probes, including cyanine dyes, donor−acceptor−donor (D−A−D) AIE structures, 25,26 and BODIPY dyes have been designed and synthesized. 27 However, most of dye molecules exhibit small Stokes shifts (<70 nm), which requires their absorption band to be located in or very near the NIR-II region.…”