Immunomodulatory nanodiamond aggregate-based platform for the treatment of rheumatoid arthritis.

Amanda Pentecost,Min Ju Kim,Young Ji Ko,Kara L Spiller,Kwangmeyung Kim,Sangmin Jeon,Ick Chan Kwon,Yury Gogotsi

doi:10.1093/rb/rbz012

Abstract

We previously demonstrated that octadecylamine-functionalized nanodiamond (ND-ODA) and dexamethasone (Dex)-adsorbed ND-ODA (ND-ODA–Dex) promoted anti-inflammatory and pro-regenerative behavior in human macrophages in vitro. In this study, we performed a pilot study to investigate if these immunomodulatory effects translate when used as a treatment for rheumatoid arthritis in mice. Following local injection in limbs of mice with collagen type II-induced arthritis, microcomputed tomography showed that mice treated with a low dose of ND-ODA and ND-ODA–Dex did not experience bone loss to the levels observed in non-treated arthritic controls. A low dose of ND-ODA and ND-ODA–Dex also reduced macrophage infiltration and expression of pro-inflammatory mediators iNOS and tumor necrosis factor-α compared to the arthritic control, while a high dose of ND-ODA increased expression of these markers. Overall, these results suggest that ND-ODA may be useful as an inherently immunomodulatory platform, and support the need for an in-depth study, especially with respect to the effects of dose.

Highlights

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects over 24 million people worldwide [1]
We showed that bath sonication and filtering can break down these agglomerates such that the aggregate size is primarily within the 1–3 lm range [36], which is optimal for macrophage uptake [50]
The transmission electron microscopy (TEM) images of de-aggregated ND-ODA confirm that these aggregates are made of individual ND-ODA particles that are 5.1 6 2.2 nm in diameter (Fig. 2C)

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects over 24 million people worldwide [1]. It is characterized by the presence of excessive inflammation at the joints, which results in swelling, stiffness and constant pain. RA pathology stems from synovial infiltration and activation of a variety of immune cells, including macrophages, dendritic cells, mast cells, T cells and B cells [2]. Activated macrophages are one of the main producers of potent proinflammatory cytokines including tumor necrosis factor-a (TNF-a). The extent of macrophage infiltration and activation corresponds directly with the RA inflammatory status, degree of surrounding destruction and overall prognosis [10, 11]. More recently it has become appreciated that depending on their phenotype, macrophages can act as crucial

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Conclusion