A biomimetic,triggered-release micelle formulation of methotrexate and celastrol controls collagen-induced arthritis in mice  

作　　者：He Ren Zewen Wu Jingxuan Li Nan Zhang Coo Yee Nah Jiexin Li Jingyu Zhang Jonathan F.Lovell Liyun Zhang Yumiao Zhang 

机构地区：[1]School of Chemical Engineering and Technology,Key Laboratory of Systems Bioengineering(Ministry of Education),Tianjin University,Tianjin,China [2]Third Hospital of Shanxi Medical University,Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital,Taiyuan,China [3]Department of Biomedical Engineering,The State University of New York at Buffalo,Buffalo,USA

出　　处：《BMEMat(BioMedical Engineering Materials)》2024年第4期130-141,共12页生物医学工程材料(英文)

基　　金：This work was supported by the National Natural Science Foundation of China(22375144 and 32071384);the National Key Research and Development Program(2021YFC2102300);the basic research project of Shanxi Science and Technology Department(202103021224342);Key Research and Development(R&D)Projects of Shanxi Province(2021XM01).

摘　　要：Rheumatoid arthritis(RA)is a systemic autoimmune disease that leads to the destruction of articular cartilage and bone.RA is characterized by immune cell infiltration and abnormal proliferation of synoviocytes in the joints.Herein,we developed a biomimetic formulation via co-loading the anti-inflammatory agent Celastrol(Cel)along with the stabilizer Vitamin K(VK)in antirheumatic methotrexate(MTX)-conjugated Pluronic F127(F127)micelles.Micelles were then coated with B cell derived membrane,yielding MTX loaded Cel Micelle(CeViM)-micelle@B,which were investigated for RA treatment.VK,used at levels well within safety margins,was identified as a carrier compound that could stabilize Cel within micelles,increasing the encapsulation efficiency of Cel.In addition,MTX,a front-line RA therapeutic,was chemically grafted to F127 via a responsive linker sensitive to the chemically reducing environments.As such,CeViM-micelle@B released pristine MTX in response to the intracellular reducing environments,which combined with Cel to suppress pro-inflammatory responses.B cell membrane coating enhanced accumulation of CeViM-micelle@B in joints,leading to a 75%decrease of inflammatory cytokine secretion in vitro,and significantly ameliorated cartilage and bone structures in the collagen-induced arthritis murine model.Taken together,this biomimetic nanoparticle holds potential as a nextgeneration targeted RA treatment.

关 键 词：co-loading MICELLE microenvironment-responsive rheumatoid arthritis self-immolative 

分 类 号：R71[医药卫生—妇产科学]