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  

作　　者：Junjie Chen Longqi Chen Zunpan She Fang Zeng Shuizhu Wu 

机构地区：[1]Biomedical Division,State Key Laboratory of Luminescent Materials and Devices,Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates,College of Materials Science and Engineering,South China University of Technology,Guangzhou,China

出　　处：《Aggregate》2024年第1期353-366,共14页聚集体（英文）

基　　金：NSFC,Grant/Award Numbers:22274057,21875069,21788102;Guangdong Provincial Basic and Applied Basic Research Fund Regional Joint Fund Project(Youth Fund Project),Grant/Award Number:2022A1515110842;Chinese Postdoctoral Science Foundation,Grant/Award Number:2022M711194。

摘　　要：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 [e-mail] intravenous injection into mice,TPC-U@HAT accumulates at inflamed lesions of RA through both active and passive targeting,and the overexpressed hyaluronidase and H_(2)O_(2) 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.

关 键 词：aggregation-induced emission dual-stimuli response multispectral optoacoustic tomography imaging multitargeting NIR-II fluorescence imaging rheumatoid arthritis 

分 类 号：O62[理学—有机化学]