title: Hyaluronate-gold nanoparticle/tocilizumab complex for the treatment of rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is a chronic inflammatory immune disease causing the inflammation of synovial membrane and the articular cartilage destruction. In this work, hyaluronate-gold nanoparticle/Tocilizumab (HA-AuNP/TCZ) complex was prepared for the treatment of RA. AuNP was used as a drug carrier with antiangiogenic effect. TCZ is a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor and used as an immunosuppressive drug by interfering IL-6 in the pathogenesis of RA. HA is known to have cartilage-protective and lubricant effects. HA was modified with cystamine via reductive amination, which was reduced with dithiothreitol (DTT) to prepare end-group thiolated HA (HA-SH). AuNP was chemically modified with HA-SH and physically modified with TCZ. The formation of HA-AuNP/TCZ complex was corroborated by UV-vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). The therapeutic effect of HA-AuNP/TCZ complex on RA was confirmed in collagen-induced arthritis (CIA) model mice by ELISA, histological, and Western blot analyses.
authors.affiliation: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH) , 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk 790-784, Korea.
authors.forename: Hwiwon
authors.initials: H
authors.lastname: Lee
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Suk Ho
authors.initials: SH
authors.lastname: Bhang
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
authors.forename: Yun Seop
authors.initials: YS
authors.lastname: Kim
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Ju
authors.forename: Ki Su
authors.initials: KS
authors.lastname: Kim
authors.forename: Sei Kwang
authors.initials: SK
authors.lastname: Hahn
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002356:Cartilage / Q000737:chemistry; D002358:Cartilage, Articular / Q000473:pathology; D003094:Collagen / Q000737:chemistry; D004229:Dithiothreitol / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D006046:Gold / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000737:chemistry; D007249:Inflammation / Q000473:pathology; D015850:Interleukin-6 / Q000737:chemistry; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008811:Mice, Inbred DBA; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology / Q000379:methods*; D013056:Spectrophotometry, Ultraviolet; D013583:Synovial Membrane / Q000187:drug effects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D006046:Gold; D006820:Hyaluronic Acid; D003094:Collagen; C502936:tocilizumab; D004229:Dithiothreitol