Reactive oxygen species and nitric oxide scavenging nanoparticles alleviating rheumatoid arthritis through adjusting the seeds and growing soils  

作　　者：Peng Hua Ruifeng Liang Yanbei Tu Yuying Yin Man-Kay Law Meiwan Chen 

机构地区：[1]State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macao,Macao SAR,China [2]State Key Laboratory of Analog and Mixed-Signal VLSI,IME and FST-ECE,University of Macao,Macao SAR,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第12期5016-5029,共14页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(51922111,82204724);the Science and Technology Development Fund,Macao SAR(File no.0124/2019/A3 and SKL-QRCM(UM)-2023-2025,China);the University of Macao(File no.MYRG2022-00203-ICMS,China).

摘　　要：Normalizing inflamed soils including reactive oxygen species(ROS),nitric oxide(NO),cellfree DNA,and regulating infammation-related seeds such as macrophages,neutrophils,fibroblasts,represent a promising strategy to maintain synovial tissue homeostasis for rheumatoid arthritis(RA)treatment.Herein,ROS scavenging amphiphilic block copolymer PEGylated bilirubin and NO-scavenging PEGylated o-phenylenediamine were fabricated to self-assemble into a dually responsive nanoparticle loaded with JAK inhibitor notopterol(Not@BR/oPDA-PEG,NBOP NPs).The simultaneous ROS and NO depletion combined with JAK-STAT pathway inhibition could not only promote M2 polarization to reduce further ROS and NO generation,but also decrease cytokines and chemokines to prevent immune cell recruitment.Specifically,NBOP NPs responded to high level ROS and NO,and disintegrated to release notopterol in inflamed joints as the hydrophobic heads BR and oPDA were transformed into hydrophilic ones.The released notopterol could inhibit the JAK-STAT pathway of infammatory cells to reduce the secretion of pro-inflammatory cytokines and chemokines.This strategy represented an effective way to regulate RA soils and seeds through breaking the positive feedback loop of inflammation aggravation,achieving an excellent anti-RA efficacy in a collagen-induced arthritis rat model.Taken together,our work offered a reference to adjust RA soils and seeds for enhanced RA treatment.

关 键 词：BILIRUBIN O-PHENYLENEDIAMINE Notopterol ROS and NO scavenging JAK-STATpathway ANTI-INFLAMMATORY Cartilage protection Rheumatoid arthritis 

分 类 号：R965[医药卫生—药理学]