Rheumatoid arthritis can be treated with a hybrid nanoparticle system

Rheumatoid arthritis can be treated with a hybrid nanoparticle system

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

Their study is published in Nature nanotechnology.

Scientists have developed a nanoparticle-based platform for the treatment of rheumatoid arthritis that involves ceria nanoparticles (Ce NPs) immobilized on mesenchymal stem cell-derived nanovesicles (MSCNVs).

Rheumatoid arthritis is a chronic inflammatory autoimmune disease for which there is no cure. The disease leads to a combination of disturbing symptoms and mechanisms, such as arthritis, production of harmful cytokines, and immune system imbalance, which work together to create a relentless cycle of worsening symptoms. Moreover, the authors point out that although the etiology of RA remains unclear, these factors have been shown to act cooperatively, creating a vicious cycle with inevitable effects on the occurrence and development of RA.

So, while targeting some of the factors involved may provide short-term relief, other contributing factors remain unresolved, leading to a frustrating cycle of remission and relapse. First-line treatment usually involves the use of anti-inflammatory drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), and biologic agents, but these “focus only on relieving symptoms,” investigators stated, and may only be temporarily effective. .

In essence, the ideal treatment for rheumatoid arthritis should not only provide immediate relief from inflammation and symptoms, but also address the root cause by returning the immune system to its normal, balanced state. “Ideal treatment for rheumatoid arthritis should include restoration of normal immune function and prompt suppression of inflammatory responses and symptoms,” the team noted. “…Multifunctional intervention systems that can inhibit multiple pathogenic factors for comprehensive rheumatoid arthritis treatment are in high demand.”

The ability to restore the immune system to a healthy state remains one of the major hurdles in treating rheumatoid arthritis. “…the balance between T helper 17 (TH17) cells and Treg cells is known to be critical in the pathogenesis of autoimmune and inflammatory diseases, especially in rheumatoid arthritis,” the researchers noted. Without this balance, the body may not be able to control the constant production of harmful substances such as reactive oxygen species (ROS) and inflammatory cytokines, leading to persistent inflammation and discomfort.

The new platform developed by Ko and colleagues involves immobilizing ceria nanoparticles onto nanovesicles derived from mesenchymal stem cells. Each of these components can inhibit different pathogens, allowing them to act individually, but also cooperatively. Ce NPs can eliminate overproduced ROS in knee joints affected by RA. It also stimulates the polarization of M1 to M2 macrophages, bringing immediate relief from inflammation and symptoms. MSCNVs deliver immunomodulatory cytokines, which convert dendritic cells (DCs) into tolerogenic dendritic cells (tDCs). This generates regulatory T cells for long-term immune tolerance. The combination of both parts in Ce-MSCNV nanoparticles aims to bridge both innate and adaptive immunity to achieve short-term pain relief, as well as shifting the tissue environment to a tolerogenic immune state to prevent recurrence of symptoms.

The authors further explained, “These two main components (Ce NPs and MSCNVs) of Ce-MSCNV work individually and synergistically to create synergy, providing rapid treatment of damaged joints, modulating immune cells and restoring disturbed T balance.”H17/Treg percentage of cells.

In their published study, the researchers demonstrated the effectiveness of the nanotherapeutic approach in a mouse model of collagen-induced arthritis. “Our goal was to break the vicious cycle of RA by creating a treatment that is immune to complications caused by synovial inflammation, harmful cytokines, and immune tolerance,” they wrote. In vivo tests showed that the Ce-MSCNV system was able to comprehensively treat and prevent rheumatoid arthritis in mice by simultaneously attenuating and restoring immediate T-cell immunity. Supporting data indicate that improvement in conditions can be achieved after just a single dose treatment. “The outstanding efficacy of Ce-MSCNVs was verified not only by immediate and sustained therapeutic effects on CIA, but also by meaningful achievement through single-dose treatment and successful prevention of CIA,” the scientists noted.

Illustration of systemic and combination RA therapy
Schematic illustration of comprehensive and combination RA treatment by Ce-MSCNV nanoparticles. Ce-MSCNVs scavenge overproduced ROS in the RA knee joint, stimulate macrophage polarization from M1 to M2 to immediately alleviate inflammation and symptoms, modulate DCs into tDCs, and finally stimulate Tregs. (Institute of Basic Sciences)

Mice treated with the Ce-MSCNV combination performed significantly better compared to animals treated with Ce NP or MSCNV alone. This clearly demonstrates the synergism between anti-inflammation and immunomodulation, and underscores the importance of combination therapy for effective RA treatment. “Ce-MSCNVs immediately inhibit inflammation, creating a favorable environment for immune tolerance, thus restoring the immune system via induction of Treg cells through modulation of immune cells,” the team stated. In addition, administration of Ce-MSCNV prior to booster injection significantly reduced the incidence and severity of symptoms, supporting the protective potential of these nanoparticles. “Collectively, our data show that administration of Ce-MSCNV before booster injection in a CIA mouse model significantly reduced disease incidence and severity by systemic treatment, supporting the preventive potential of Ce-MSCNV for rheumatoid arthritis,” the researchers reported.

“One of the most difficult decisions in treating refractory disease is deciding how long treatment should be continued,” said first author KOO Sagang. “For rheumatoid arthritis, it would not be appropriate to stop treatment just because the target marker has stabilized. The safest indication should be that the ingredients The innate and adaptive immune systems are normalized to protect the body.

The scientists suggest that their study demonstrates the potential of the hybrid nanoparticle system in the comprehensive treatment of autoimmune diseases and modulation of the immune system.

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