Inflammation-Targeting Fullerene Nanoparticles Dually Inhibit Macrophage and Osteoclast Differentiation for Mitigating Rheumatoid Arthritis  

作　　者：Lei Liu Xue Li Zhanfeng Wu Libin Yang Jiawei Huo Shaojian Tang Xinran Cao Yuan Xu Xiaodan Liao Hedong Qi Jie Li Jingchao Liu Jianxin Tian Rui Wen Chunru Wang Chunli Bai 

机构地区：[1]Key Laboratory of Molecular Nanostructure and Nanotechnology,Beijing National Laboratory for Molecular Sciences,CAS Research/Education Center for Excellence in Molecular Sciences,Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190 [2]University of Chinese Academy of Sciences,Beijing 100049 [3]School of Pharmacy,Weifang Medical University,Weifang 261053

出　　处：《CCS Chemistry》2024年第9期2275-2288,共14页中国化学会会刊（英文）

基　　金：supported by the National Natural Science Foundation of China(grant no.52272048);the Beijing Natural Science Foundation(grant no.2222090);the Ministry of Science and Technology of China(grant no.2022YFA1205900),the Key Research Program of the Chinese Academy of Sciences(grant no.QYKJZD-SSW-SLH01);Natural Science Foundation of Shandong Province(grant no.ZR2020QB016).

摘　　要：In rheumatoid arthritis(RA),the presence of substantial inflammatory macrophages and osteoclasts in joints is known to contribute to the progression of articular inflammation and bone destruction.Herein,we develop a sialic acid-modified tetra malonic acid derivative of C70 fullerene(STMF).STMF possesses inflammation-targeting capability that can effectively impede the differentiation of macrophages and osteoclasts,offering a potential treatment strategy for RA.STMF acts as a mimic of sialyl Lewis x,enabling it to specifically bind with E-selectin,which is overexpressed on inflamed endothelial cells.This selective binding results in a targeted distribution of STMF to inflamed joints,addressing articular in-flammation.Upon uptake by macrophages,STMF demonstrates the ability to effectively eliminate intracellular reactive oxygen species and deactivate the downstream events,thereby suppressing their differentiation into M1-phenotype and osteoclastogenesis.In our experiments using collagen-induced arthritis mouse models,STMF significantly improves paw swelling and redness,mitigates articular inflammation with reduced M1 macrophages,lessens osteoclasts,and repairs bone erosion with neglectable side effects.These findings suggest that STMF has potential as a therapeutic agent for RA,leveraging inflammation-targeting fullerene nanomaterials.

关 键 词：fullerene targeting inflammation rheumatoid arthritis sialic acid MACROPHAGES OSTEOCLASTS 

分 类 号：O62[理学—有机化学]