Immune system dysfunction in rheumatoid arthritis (RA) leads to the uncontrolled production of reactive oxygen species (ROS) and inflammatory cytokines, resulting in persistent inflammation and discomfort. The optimal treatment for RA should focus on regulating inflammation while also restoring immune system function. A recent study, published in the journal Nature Nanotechnology, has introduced a novel ceria-vesicle nanohybrid therapeutic strategy for modulating both innate and adaptive immunity.
This new nanoparticle-based therapy is a collaborative effort led by Koo Sagang and his team from Seoul National University, the Centre for Nanoparticle Research at the Institute for Basic Science, and the Korea Institute of Science and Technology. The new platform involves immobilizing ceria nanoparticles (Ce NPs) onto mesenchymal stem cell-derived nanovesicles (MSCNVs). Both of these components can inhibit various pathogenic factors, allowing them to work both individually and cooperatively to achieve a comprehensive treatment.
The researchers aim to combine innate and adaptive immunity to achieve short-term pain relief and prevent the recurrence of symptoms by creating an immune-tolerant tissue environment. Ce NPs can eliminate overproduced ROS in RA-affected knee joints while also inducing the polarization of M1 macrophages into M2, offering immediate relief from inflammation and symptoms. MSCNVs deliver immunomodulatory cytokines, which transform dendritic cells (DC) into tolerogenic dendritic cells (tDCs) that generate regulatory T cells for long-term immune tolerance. The efficacy of this approach was confirmed in a mouse model of collagen-induced arthritis. The Ce-MSCNV system effectively treated and prevented RA by simultaneously providing immediate relief and restoring T-cell immunity. The data also suggest that a single-dose treatment may significantly improve conditions.
Making decisions about the duration of treatment poses a significant challenge in the context of therapy for intractable diseases, as highlighted by Koo and colleagues. In RA, it is not recommended to discontinue the treatment solely because of the stabilization of the target marker. Instead, ensuring the normalization of both the innate and adaptive components of the compromised immune system is a more reliable indicator for treatment cessation.
According to Koo, the approach adopted by the Ce-MSCNVs, which combines various treatment mechanisms, can be applied to other complex diseases involving inflammation and the immune system. The system’s components can be modified, such as using alternative catalysts to ROS or cell-derived nanovesicles. In summary, the study highlights the potential of a hybrid nanoparticle system for effectively treating autoimmune diseases and regulating the immune system.
Koo S, Sohn HS, Kim TH, Yang S, Jang SY, Ye S, et al. Ceria-vesicle nanohybrid therapeutic for modulation of innate and adaptive immunity in a collagen-induced arthritis model. Nat Nanotechnol. 2023 Oct 26;1–13.