Tag Archives: Min Soh

Nanoparticle treatment for rheumatoid arthritis

An October 26, 2023 news item on phys.org announced a possible new treatment for rheumatoid arthritis (RA), Note: Links have been removed,

A team of scientists [Korea] has developed a new solution for the treatment of rheumatoid arthritis (RA). The work has been published in Nature Nanotechnology.

RA is a chronic disease that, unfortunately, has no cure. The disease triggers a mix of troublesome symptoms like inflamed joints, harmful cytokines, and immune system imbalances, which work together to create a relentless cycle of worsening symptoms. While targeting 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 major hurdles in RA treatment is the inability to restore the immune system to its healthy state. This leaves the body unable to control the continuous production of harmful substances like reactive oxygen species (ROS) and inflammatory cytokines, leading to persistent inflammation and discomfort.

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

New nanoparticle-based system as a solution

The new platform involves immobilizing ceria nanoparticles (Ce NPs) onto mesenchymal stem cell-derived nanovesicles (MSCNVs). Both of these components can hinder different pathogenic factors, allowing them to work both individually and cooperatively to achieve a comprehensive treatment.

Caption: Schematic illustration of comprehensive and combination RA therapy by Ce-MSCNV nanoparticles. Ce-MSCNVs scavenge the over-produced ROS in an RA knee joint, induce M1 to M2 macrophage polarization for immediate relief of inflammation and symptoms, modulate DCs into tDCs, and finally induce Tregs. Credit: Institute for Basic Science

An October 27, 2023 Institute for Basic Science (IBS) press release (also on EurekAlert but published October 26, 2023), which originated the news item, provides more details about the proposed treatment,

Ce NPs – can scavenge the overproduced ROS in RA-inflicted knee joints. They also induce polarization of M1 macrophages into M2, achieving immediate relief of inflammation and symptoms.

MSCNVs – deliver immunomodulatory cytokines, which turn 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 both short-term pain relief, as well as convert the tissue environment into an immune-tolerant state to prevent the 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 relieving the immediate and restoring T cell immunity. Supporting data suggest that improvement in conditions can be achieved after only a single-dose treatment.

The mice treated with the Ce-MSCNV combination fared far better compared to the ones only treated using the Ce NP or MSCNV group. This clearly demonstrates the synergy between anti-inflammation and immunomodulation and underlines the importance of the combined therapy for effective RA treatment. In addition, Ce-MSCNV administration prior to booster injection markedly reduced the incidence and severity of symptoms, supporting the prophylactic potential of these nanoparticles.

First author KOO Sagang stated, “One of the hardest decisions in intractable disease therapy is determining how long the treatment should be carried on. For RA, it would not be appropriate to stop treatment just because the target marker is stabilized. A safer indicator should be that the innate and adaptive components of the collapsed immune system are normalized to protect the body.”

Koo believes that the strategy adopted by Ce-MSCNVs, where different treatment mechanisms work together, provides a unique advantage in this regard. Furthermore, she predicts that a similar approach would also be applicable to other intractable, inflammatory, and autoimmune diseases for this purpose. The components within the system may also be modified. For example, other catalysts for generating ROS or other cell-derived nanovesicles could be utilized depending on the types of diseases. Overall, this study proves the potential of a hybrid nanoparticle system for the comprehensive treatment of autoimmune disease and modulation of the immune system.

Here’s a link to and a citation for the paper,

Ceria-vesicle nanohybrid therapeutic for modulation of innate and adaptive immunity in a collagen-induced arthritis model by Sagang Koo, Hee Su Sohn, Tae Hee Kim, Siyeon Yang, Se Youn Jang, Seongryeol Ye, Boomin Choi, Soo Hyeon Kim, Kyoung Sun Park, Hyun Mu Shin, Ok Kyu Park, Cheesue Kim, Mikyung Kang, Min Soh, Jin Yoo, Dokyoon Kim, Nohyun Lee, Byung-Soo Kim, Youngmee Jung & Taeghwan Hyeon. Nature Nanotechnology (2023) DOI: https://doi.org/10.1038/s41565-023-01523-y Published: 26 October 2023

This paper is behind a paywall.

Ceria-zirconia nanoparticles for sepsis treatment

South Korean researchers are looking at a new way of dealing with infections (sepsis) according to a July 6, 2017 news item on phys.org,

During sepsis, cells are swamped with reactive oxygen species generated in an aberrant response of the immune system to a local infection. If this fatal inflammatory path could be interfered, new treatment schemes could be developed. Now, Korean scientists report in the journal Angewandte Chemie that zirconia-doped ceria nanoparticles act as effective scavengers of these oxygen radicals, promoting a greatly enhanced surviving rate in sepsis model organisms.

A July 6, 2017 Wiley (Publishers) press release, which originated the news item, provides more detail,

Sepsis proceeds as a vicious cycle of inflammatory reactions of the immune system to a local infection. Fatal consequences can be falling blood pressure and the collapse of organ function. As resistance against antibiotics is growing, scientists turn to the inflammatory pathway as an alternative target for new treatment strategies. Taeghwan Heyon from Seoul National University, Seung-Hoon Lee at Seoul National University Hospital, South Korea, and collaborators explore ceria nanoparticles for their ability to scavenge reactive oxygen species, which play a key role in the inflammatory process. By quickly converting between two oxidation states, the cerium ion can quench typical oxygen radical species like the superoxide anion, the hydroxyl radical anion, or even hydrogen peroxide. But in the living cell, this can only happen if two conditions are met.

The first condition is the size and nature of the particles. Small, two-nanometer-sized particles were coated by a hydrophilic shell of poly(ethylene glycol)-connected phospholipids to make them soluble so that they can enter the cell and remain there. Second, the cerium ion responsible for the quenching (Ce3+) should be accessible on the surface of the nanoparticles, and it must be regenerated after the reactions. Here, the scientists found out that a certain amount of zirconium ions in the structure helped, because “the Zr4+ ions control the Ce3+-to-Ce4+ ratio as well as the rate of conversion between the two oxidation states,” they argued.

The prepared nanoparticles were then tested for their ability to detoxify reactive oxygen species, not only in the test tube, but also in live animal models. The results were clear, as the authors stated: “A single dose of ceria-zirconia nanoparticles successfully attenuated the vicious cycle of inflammatory responses in two sepsis models.” The nanoparticles accumulated in organs where severe immune responses occurred, and they were successful in the eradication of reactive oxygen species, as evidenced with fluorescence microscopy and several other techniques. And importantly, the treated mice and rats had a far higher survival rate.

This work demonstrates that other approaches in sepsis treatment than killing bacteria with antibiotics are possible. Targeting the inflammatory signal pathways in macrophages is a very promising option, and the authors have shown that effective scavenging of reactive oxygen species and stopping inflammation is possible with a suitably designed chemical system like this cerium ion redox system provided by nanoparticles.

Here’s a link to and a citation for the paper,

Ceria–Zirconia Nanoparticles as an Enhanced Multi-Antioxidant for Sepsis Treatment by Min Soh, Dr. Dong-Wan Kang, Dr. Han-Gil Jeong, Dr. Dokyoon Kim, Dr. Do Yeon Kim, Dr. Wookjin Yang, Changyeong Song, Seungmin Baik, In-Young Choi, Seul-Ki Ki, Hyek Jin Kwon, Dr. Taeho Kim, Prof. Dr. Chi Kyung Kim, Prof. Dr. Seung-Hoon Lee, and Prof. Dr. Taeghwan Hyeon. Angewandte Chemie DOI: 10.1002/anie.201704904 Version of Record online: 5 JUL 2017

© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.