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.

Molecular targets in arthritis and recent trends in nanotherapy

“…Tocilizumab-loaded hyaluronate-gold nanoparticles targeted with a monoclonal antibody against IL-6 have also been tested in CIA mice. 95 In another study, the delivery of MTX was achieved using theranostic gold half-shell NPs targeted with RGD peptides. 96 It was revealed that a much smaller dose of these NPs showed greater therapeutic effects than that of a conventional treatment with MTX solution in CIA mice.…”

Advanced nanomedicine for rheumatoid arthritis treatment: focus on active targeting

“…Among these, the hypoxia-vascular endothelial growth factors (VEGF)-angiopoietin system plays a central role [5]. In addition, several adhesion molecules including α v β 3 integrins, E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 are over-expressed on the surface of endothelial cells [5,[7][8][9][10]. Macrophages, abundant in the inflamed synovial membrane, possess broad proinflammatory potential and contribute considerably to inflammation and joint destruction.…”

“…Currently, gold nanoparticles (AuNPs) were exploited as therapeutic treatment for rheumatic diseases attributed to their anti-inflammatory and antiangiogenic actions [17]. Inspired by this property, Lee et al [10] prepared hyaluronate-AuNPs/Tocilizumab (HA-AuNP/tocilizumab (TCZ)) complex with dual targeting effects. AuNP could actively bind to VEGF and TCZ, the first therapeutic antibody against IL-6 signaling, could target to IL-6R.…”

Translational Nano-Medicines: Targeted Therapeutic Delivery for Cancer and Inflammatory Diseases

“…The work by Lee et al is among few studies that developed a targeted delivery system for a monoclonal antibody. A stable hyaluronate/gold nanoparticle/tocilizumab (HA-AuNP/TCZ) complex was synthesized for the successful treatment of RA in mouse model (73).…”