In rheumatoid arthritis (RA), insufficient apoptosis of macrophages and excessive generation of pro-inflammatory cytokines are intimately connected, accelerating the development of disease. Here, a fluorinated polyamidoamine dendrimer (FP) is used to deliver miR-23b to reduce inflammation by triggering the apoptosis of as well as inhibiting the inflammatory response in macrophages. Following the intravenous injection of FP/miR-23b nanoparticles in experimental RA models, the nanoparticles show therapeutic efficacy with inhibition of inflammatory response, reduced bone and cartilage erosion, suppression of synoviocyte infiltration and the recovery of mobility. Moreover, the nanoparticles accumulate in the inflamed joint and are non-specifically captured by synoviocytes, leading to the restoration of miR-23b expression in the synovium. The miR-23b nanoparticles target Tab2, Tab3 and Ikka to regulate the activation of NF-kappa B pathway in the hyperplastic synovium, thereby promoting anti-inflammatory and anti-proliferative responses. Additionally, the intravenous administration of FP/miR-23b nanoparticles do not induce obvious systemic toxicity. Overall, our work demonstrates that the combination of apoptosis induction and inflammatory inhibition could be a promising approach in the treatment of RA and possibly other autoimmune diseases.
机构:
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun,130012, ChinaKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun,130012, China
Xing, Jiakai
Jia, Jiaxin
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Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun,130012, ChinaKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun,130012, China
Jia, Jiaxin
Zhang, Hugang
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Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun,130012, ChinaKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun,130012, China
Zhang, Hugang
Han, Haobo
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Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun,130012, ChinaKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun,130012, China
机构:
Sichuan Univ, West China Hosp, Dept Orthopaed Surg, 37 Guoxue Rd, Chengdu 610041, Peoples R China
Beijing Jishuitan Hosp, Dept Spine Surg, Guizhou Hosp, 206 Sixian Rd, Guiyang 550014, Peoples R ChinaSichuan Univ, West China Hosp, Dept Orthopaed Surg, 37 Guoxue Rd, Chengdu 610041, Peoples R China
Wang, Lihang
Wang, Yun
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Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, State Key Lab Oral Dis,Natl Ctr Stomatol, 37 GuoXue Rd, Chengdu 610041, Peoples R ChinaSichuan Univ, West China Hosp, Dept Orthopaed Surg, 37 Guoxue Rd, Chengdu 610041, Peoples R China
Wang, Yun
Lu, Tingsheng
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Beijing Jishuitan Hosp, Dept Spine Surg, Guizhou Hosp, 206 Sixian Rd, Guiyang 550014, Peoples R ChinaSichuan Univ, West China Hosp, Dept Orthopaed Surg, 37 Guoxue Rd, Chengdu 610041, Peoples R China
Lu, Tingsheng
Luo, Chunshan
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Beijing Jishuitan Hosp, Dept Spine Surg, Guizhou Hosp, 206 Sixian Rd, Guiyang 550014, Peoples R ChinaSichuan Univ, West China Hosp, Dept Orthopaed Surg, 37 Guoxue Rd, Chengdu 610041, Peoples R China
Luo, Chunshan
Qiu, Bing
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机构:
Beijing Jishuitan Hosp, Dept Spine Surg, Guizhou Hosp, 206 Sixian Rd, Guiyang 550014, Peoples R ChinaSichuan Univ, West China Hosp, Dept Orthopaed Surg, 37 Guoxue Rd, Chengdu 610041, Peoples R China
Qiu, Bing
Huang, Shishu
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Sichuan Univ, West China Hosp, Dept Orthopaed Surg, 37 Guoxue Rd, Chengdu 610041, Peoples R ChinaSichuan Univ, West China Hosp, Dept Orthopaed Surg, 37 Guoxue Rd, Chengdu 610041, Peoples R China
Huang, Shishu
Lin, Yunfeng
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Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, State Key Lab Oral Dis,Natl Ctr Stomatol, 37 GuoXue Rd, Chengdu 610041, Peoples R China
Sichuan Prov Engn Res Ctr Oral Biomat, Chengdu 610041, Sichuan, Peoples R ChinaSichuan Univ, West China Hosp, Dept Orthopaed Surg, 37 Guoxue Rd, Chengdu 610041, Peoples R China