Novel nanoparticle-based system developed for the comprehensive treatment of rheumatoid arthritis

A team of scientists led by KOO Sagang of Seoul National University and the Center for Nanoparticle Research within the Institue for Basic Science Center (IBS), in collaboration with researchers from the Korea Institute of Science and Technology (KIST) and the Seoul National University, developed a new solution for the treatment of rheumatoid arthritis (RA).

RA is a chronic disease that unfortunately cannot be cured. The disease causes a mix of troublesome symptoms, such as inflamed joints, harmful cytokines, and immune system imbalances, which work together to create a relentless cycle of worsening symptoms. While addressing some of these factors can provide short-term relief, others remain unresolved, leading to a frustrating cycle of remission and flare-ups.

One of the biggest hurdles in treating RA is the inability to restore the immune system to a healthy state. This leaves the body unable to control the continued production of harmful substances such as reactive oxygen species (ROS) and inflammatory cytokines, leading to persistent inflammation and discomfort.

Essentially, the ideal treatment for RA should not only provide immediate relief from inflammation and symptoms, but also address the cause by restoring the immune system to its normal, balanced state.

New nanoparticle-based system as a solution

The novel platform involves immobilizing ceria nanoparticles (Ce NPs) on mesenchymal stem cell-derived nanovesicles (MSCNVs). Both components can hinder various pathogenic factors, allowing them to work individually and together to achieve comprehensive treatment.

Ce NPs – can scavenge the overproduction of ROS in RA-induced knee joints. They also cause polarization of M1 macrophages into M2, immediately relieving inflammation and symptoms.

MSCNVs – deliver immunomodulatory cytokines, which convert dendritic cells (DC) into tolerogenic dendritic cells (tDCs). This consequently generates regulatory T cells for long-term immune tolerance.

In short, this approach aims to bridge both innate and adaptive immunity to achieve short-term pain relief, and to convert the tissue environment into an immune-tolerant state to prevent recurrence of symptoms.

Researchers confirmed the efficacy of this approach using a collagen-induced arthritis mouse model. The Ce-MSCNV system was able to comprehensively treat and prevent RA by simultaneously easing and restoring immediate T cell immunity. Supporting data suggests that improvement in conditions can be achieved after only a single dose treatment.

The mice treated with the Ce-MSCNV combination did much better compared to the mice treated with the Ce NP or MSCNV group alone. This clearly demonstrates the synergy between anti-inflammatory agents and immunomodulation and underlines the importance of the combined therapy for effective treatment of RA. Furthermore, administration of Ce-MSCNV prior to booster injection significantly reduced the incidence and severity of symptoms, supporting the prophylactic potential of these nanoparticles.

One of the most difficult decisions in the treatment of intractable diseases is determining how long to continue treatment. For RA, it would not be appropriate to stop treatment just because the target marker has stabilized. A safer indicator should be that the innate and adaptive components of the collapsed immune system are normalized to protect the body.”

Koo Sagang, first author

Koo believes that Ce-MSCNVs’ strategy of working together with different treatment mechanisms offers a unique advantage in this regard. Furthermore, she predicts that a similar approach for this purpose would also be applicable to other refractory, inflammatory and autoimmune diseases. The components within the system can also be changed. For example, depending on the type of disease, other catalysts can be used to generate ROS or other cell-derived nanovesicles. Overall, this study proves the potential of a hybrid nanoparticle system for the comprehensive treatment of autoimmune diseases and modulation of the immune system.