Inhibition of Inflammatory Arthritis Using Fullerene Nanomaterials

Abstract

Inflammatory arthritis (e.g. rheumatoid arthritis; RA) is a complex disease driven by the interplay of multiple cellular lineages. Fullerene derivatives have previously been shown to have anti-inflammatory capabilities mediated, in part, by their ability to prevent inflammatory mediator release by mast cells (MC). Recognizing that MC can serve as a cellular link between autoantibodies, soluble mediators, and other effector populations in inflammatory arthritis, it was hypothesized that fullerene derivatives might be used to target this inflammatory disease. A panel of fullerene derivatives was tested for their ability to affect the function of human skin-derived MC as well as other lineages implicated in arthritis, synovial fibroblasts and osteoclasts. It is shown that certain fullerene derivatives blocked FcγR- and TNF-α-induced mediator release from MC; TNF-α-induced mediator release from RA synovial fibroblasts; and maturation of human osteoclasts. MC inhibition by fullerene derivatives was mediated through the reduction of mitochondrial membrane potential and FcγR-mediated increases in cellular reactive oxygen species and NF-κB activation. Based on these in vitro data, two fullerene derivatives (ALM and TGA) were selected for in vivo studies using K/BxN serum transfer arthritis in C57BL/6 mice and collagen-induced arthritis (CIA) in DBA/1 mice. Dye-conjugated fullerenes confirmed localization to affected joints in arthritic animals but not in healthy controls. In the K/BxN moldel, fullerenes attenuated arthritis, an effect accompanied by reduced histologic inflammation, cartilage/bone erosion, and serum levels of TNF-α. Fullerenes remained capable of attenuating K/BxN arthritis in mast cell-deficient mice Cre-Master mice, suggesting that lineages beyond the MC represent relevant targets in this system. These studies suggest that fullerene derivatives may hold promise both as an assessment tool and as anti-inflammatory therapy of arthritis.

Nanoparticle fullerol alleviates radiculopathy via NLRP3 inflammasome and neuropeptides

“…32–35 In our study, we created a mouse model of autologous tail disc NP implantation with some modifications. Since mouse NP is tiny and very soft, we included a small portion of inner AF with the NP.…”

“…Numerous studies have reported their radical scavenging activities and anti-inflammatory properties via reduction of ROS levels and regulation of the NF-kB signaling pathways. 35 It has been reported to ameliorate inflammatory responses in arthritis and disc herniation models. 14,17,18 In the current radiculopathy model, fullerol diminished the release of inflammatory mediators (Figure 6) when disc NPs were bathed in fullerol solution prior to implantation.…”

Recent Advances in Nanotheranostics for Treat‐to‐Target of Rheumatoid Arthritis

“…Dellinger et al tested the ability of fullerene affecting the lineages implicated in arthritis, synovial fibroblasts, and osteoclasts. The study revealed that certain fullerene reduced TNF‐α‐induced mediator release from mast cells 98. Jia et al developed an inflammation‐targeted delivery system based on a liposomal carrier‐loaded Dex against arthritis 51.…”

Move to Nano‐Arthrology: Targeted Stimuli‐Responsive Nanomedicines Combat Adaptive Treatment Tolerance (ATT) of Rheumatoid Arthritis

“…The in vivo fluorescence imaging confirmed the inflamed joints specific accumulation of fullerene derivatives via EPR‐like effect. Benefiting from the favorable targeting ability, the fullerene derivatives effectively attenuated arthritis with reduced histologic inflammation and cartilage erosion, which suggested the fullerene derivatives as promising NMs to overcome the ATT of RA and achieve efficacious therapy for arthritis …”