Nanoparticles: Flattening the Curve and Type 1 Diabetes
By: James LeFevre
Currently, a lot of ongoing research has focused on the COVID-19 pandemic in order to “flatten the curve.” Unintentionally, this diverted attention has provided new advancements for type 1 diabetes (T1D), one of which is nanoparticles that may not only prove useful to “flatten the curve” but also to flatten T1D.
Given that T1D is an autoimmune disease, treatments that can suppress the autoreactivity of the immune system are valuable. Even further, treatments that can suppress the autoreactivity associated with T1D, without suppressing the rest of the entire immune system, are even more valuable. In the future, nanoparticles may be used to mediate this type of therapy by suppressing beta-cell attack while simultaneously leaving the rest of the immune system unaffected. For once, being picky is a good thing.
In the context of the immune system, nanoparticles may act as artificial antigen presenting cells, and may be coated with proteins and peptides to elicit calculated immune responses. With the right coat design, nanoparticles may modulate beta cell attack and prevent further progression of T1D.
Nanoparticles as Antiviral and Immune System Modulating Technology
In a study by Rao and colleagues, nanoparticles were designed to express various surface proteins and tested for their antiviral and cytokine neutralizing capabilities. Specifically, they were designed with angiotensin converting enzyme 2 receptors (ACE2), interleukin-6 receptors (IL-6R), and Granulocyte-macrophage colony-stimulating factor receptors (GM-CSFR). The nanoparticles were derived by fusing cellular membrane nanovesicles from genetically edited 293T/ACE2 and THP-1 cells.
Figure 1. Nanoparticle derived from genetically edited 293T/ACE2 and THP-1 cells designed with an ACE2, IL-6R, and GM-CSFR coating.
The researchers used human hepatoma Huh-7 cells for in vitro experimentation and an acute lung inflammation mouse model for in vivo experimentation. The nanoparticles:
- Inhibited in vitro pseudovirus and authentic SARS-CoV-2 infection.
- Neutralized inflammatory cytokines in vitro.
- Suppressed acute pneumonia in vivo.
These promising results show that nanoparticles can serve as antiviral and immune system modulating technology. Likewise, given that nanoparticles are customizable, they may prove to be a promising treatment for T1D as well. So, how might nanoparticles be designed to curtail or cure the beta-cell attack in T1D?
Nanoparticles as antidiabetic therapy
Jamison and colleagues have used poly(lactide-co-glycolide) (PLG) nanoparticles loaded with 2.5HIP, a hybrid insulin peptide (HIP), to alter diabetogenic components of the immune system in non-obese diabetic (NOD) mice. Figure 2 shows a depiction of the nanoparticle design.
Figure 2. Poly(lactide-co-glycolide) (PLG) nanoparticle loaded with 2.5HIP.
The nanoparticles were administered intravenously and lead to the following results:
- The 2.5HIP loaded nanoparticles successfully tolerized BDC-2.5 T cells and prevented the transfer of diabetes into NOD mice.
- The induced tolerance led to the accumulation of T cells in the spleen and reduced trafficking to pancreatic islets.
- Nanoparticles loaded with 2.5HIP were more effective in inducing tolerance than using 2.5HIP alone.
- Proinflammatory cytokine production from BDC-2.5 effector T cells were impaired after inducing tolerance.
Overall, the study shows nanoparticles are a promising therapeutic approach that may help prevent or reverse type 1 diabetes. In contrast, T1D is a complex autoimmune disease that involves several autoantigens. The researchers note that testing their findings in an NOD spontaneous model will be critical.
The Takeaway: Nanoparticles are a promising therapeutic approach. Further understanding of the autoantigens involved in type 1 diabetes will be crucial in developing nanoparticle technology. Although beta cell damage may be stopped with nanoparticles, beta cells must still be replaced. Subsequently, future treatments may involve nanoparticles combined with islet cell transplantation.
- Rao, L., Xia, S., Xu, W., Tian, R., Yu, G., Gu, C., … Chen, X. (2020). Decoy nanoparticles protect against COVID-19 by concurrently adsorbing viruses and inflammatory cytokines. Proceedings of the National Academy of Sciences, 117(44), 27141–27147. https://doi.org/10.1073/pnas.2014352117
- Jamison, B. L., Neef, T., Goodspeed, A., Bradley, B., Baker, R. L., Miller, S. D., & Haskins, K. (2019). Nanoparticles Containing an Insulin–ChgA Hybrid Peptide Protect from Transfer of Autoimmune Diabetes by Shifting the Balance between Effector T Cells and Regulatory T Cells. The Journal of Immunology, 203(1), 48–57. https://doi.org/10.4049/jimmunol.1900127