Hyaluronate-Gold Nanoparticle/Tocilizumab Complex for the Treatment of Rheumatoid Arthritis

被引：183
作者：
Lee, Hwiwon [1 ]
Lee, Min-Young [1 ]
Bhang, Suk Ho [2 ]
Kim, Byung-Soo [2 ]
Kim, Yun Seop [1 ]
Ju, Ji Hyeon [3 ]
Kim, Ki Su [4 ,5 ]
Hahn, Sei Kwang [1 ]
机构：
[1] Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, Pohang 790784, Kyungbuk, South Korea
[2] Seoul Natl Univ, Sch Chem & Biol Engn, Seoul 151744, South Korea
[3] Catholic Univ Korea, Coll Med, Dept Internal Med, Seoul 137701, South Korea
[4] Harvard Univ, Sch Med, Wellman Ctr Photomed, Cambridge, MA 02139 USA
[5] Massachusetts Gen Hosp, Cambridge, MA 02139 USA
来源：
ACS NANO | 2014年 / 8卷 / 05期
基金：
新加坡国家研究基金会;
关键词：
gold nanoparticle; tocilizumab; hyaluronic acid; drug delivery; rheumatoid arthritis; COLLAGEN-INDUCED ARTHRITIS; RECEPTOR INHIBITION; NANOPARTICLES; TOCILIZUMAB; THERAPY; ACID; DISEASE;
D O I：
10.1021/nn500685h
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
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. in 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 T. 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.
引用
收藏
页码：4790 / 4798
页数：9
相关论文
共 32 条
[1]   Gold nanoparticles inhibit VEGF165-induced proliferation of HUVEC cells [J].
Bhattacharya, R ;
Mukherjee, P ;
Xiong, Z ;
Atala, A ;
Soker, S ;
Mukhopadhyay, D .
NANO LETTERS, 2004, 4 (12) :2479-2481
[2]   Collagen-induced arthritis [J].
Brand, David D. ;
Latham, Kary A. ;
Rosloniec, Edward F. .
NATURE PROTOCOLS, 2007, 2 (05) :1269-1275
[3]   Photoacoustic tomography of joints aided by an Etanercept-conjugated gold nanoparticle contrast agent -: an ex vivo preliminary rat study [J].
Chamberland, David L. ;
Agarwal, Ashish ;
Kotov, Nicholas ;
Fowlkes, J. Brian ;
Carson, Paul L. ;
Wang, Xueding .
NANOTECHNOLOGY, 2008, 19 (09)
[4]   Evolving concepts of rheumatoid arthritis [J].
Firestein, GS .
NATURE, 2003, 423 (6937) :356-361
[5]   Gold nanoparticles in delivery applications [J].
Ghosh, Partha ;
Han, Gang ;
De, Mrinmoy ;
Kim, Chae Kyu ;
Rotello, Vincent M. .
ADVANCED DRUG DELIVERY REVIEWS, 2008, 60 (11) :1307-1315
[6]   Gold Nanoparticles for Biology and Medicine [J].
Giljohann, David A. ;
Seferos, Dwight S. ;
Daniel, Weston L. ;
Massich, Matthew D. ;
Patel, Pinal C. ;
Mirkin, Chad A. .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2010, 49 (19) :3280-3294
[7]  
Häkkinen H, 2012, NAT CHEM, V4, P443, DOI [10.1038/NCHEM.1352, 10.1038/nchem.1352]
[8]   Receptor-Fc fusion therapeutics, traps, and MIMETIBODY™ technology [J].
Huang, Chichi .
CURRENT OPINION IN BIOTECHNOLOGY, 2009, 20 (06) :692-699
[9]   Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: Applications in biological imaging and biomedicine [J].
Jain, PK ;
Lee, KS ;
El-Sayed, IH ;
El-Sayed, MA .
JOURNAL OF PHYSICAL CHEMISTRY B, 2006, 110 (14) :7238-7248
[10]   Gold nanoparticle (AuNP)-based drug delivery and molecular imaging for biomedical applications [J].
Jeong, Eun Hye ;
Jung, Giyoung ;
Hong, Cheol Am ;
Lee, Hyukjin .
ARCHIVES OF PHARMACAL RESEARCH, 2014, 37 (01) :53-59
1234