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

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Acta Pharmaceutica Sinica B 2023年第12期13卷 5016-5029页

作者： Peng Hua Ruifeng Liang Yanbei Tu Yuying Yin Man-Kay Law Meiwan Chen State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina State Key Laboratory of Analog and Mixed-Signal VLSI IME and FST-ECEUniversity of MacaoMacao SARChina

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)***,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 ***,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 *** released notopterol could inhibit the JAK-STAT pathway of infammatory cells to reduce the secretion of pro-inflammatory cytokines and *** 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 *** 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

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