In this article, AZoNano offers a complete guide to how nanotechnology can, and has, been used in mRNA vaccines.
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As the name suggests, nanotechnology is the manipulation of matter at the nanoscale and is involved with creating new structures, materials and products.
Nanotechnology has touched and revolutionized various fields, including medicine. The development and successful implementation of nanotechnology-enhanced messenger RNA (mRNA) vaccines is a remarkable testament to the integration of nanotechnology, which paves the way for innovative and effective approaches to disease prevention and treatment.
Fundamentals of mRNA Vaccines
mRNA vaccines represent a novel class of vaccines that utilize a small piece of genetic material, known as mRNA, which instructs cells in the body to produce target antigens, stimulating an immune response. This method, compared to traditional vaccine approaches, provides advantages such as rapid development, scalability, and improved safety profiles.
Nanotechnology's Role in Vaccine Enhancement
Nanoparticles as Delivery Vehicles
Due to their unique physicochemical properties, nanoparticles have become indispensable tools in enhancing the delivery and efficacy of mRNA vaccines. Lipid nanoparticles (LNPs) and other nanocarriers provide protection to the fragile mRNA molecules that may be broken down by ribonucleases, therefore assisting in keeping the mRNA undamaged and facilitating its delivery to the target site. In addition, LNPs also enhance cellular uptake and enable controlled release, resulting in improved vaccine stability and antigen presentation.
Tailoring Antigen Presentation
By employing nanotechnology, researchers can engineer the surface properties of nanoparticles to optimize antigen presentation to immune cells. Thus, using this tailored approach, the recognition of antigens can be augmented, ultimately leading to a heightened and more targeted immune response.
Formulation and Manufacturing
Designing Effective Nanocarriers
The formulation of mRNA vaccines involves the meticulous design of nanocarriers, which are designed to carry the delicate mRNA molecule for targeted delivery, ensuring its safe transport to target cells while evading enzymatic degradation and immune detection.
There has been a myriad of materials produced to accomplish such a task: lipids, lipid-like materials, polymers and protein derivatives. However, extensive research into lipid nanoparticles showed successful encapsulation and delivery of mRNA, and also found its way into clinical use. A more recent example of lipid nanoparticles being implemented as delivery vehicles in mRNA vaccines is the coronavirus 2019 (COVID-19) vaccines, whereby lipid nanoparticles were used to encapsulate and deliver the antigen mRNA.
The effective utilization of nanoparticles in biomedical applications relies on critical parameters such as their dimensions, form, structure, size distribution, capacity for specific targeting, and functional attributes. Hence, the production of nanotechnology-enhanced mRNA vaccines requires stringent quality control measures in order to ensure reproducibility, purity, and consistency in the formulation and assembly of nanoparticles, guaranteeing both safety and efficacy.
Mechanism of Action
Nanotechnology-Mediated Uptake and Stimulating Immune Response
Upon administration, nanotechnology-enhanced mRNA vaccines employ various mechanisms to enter target cells, including membrane fusion and endocytosis. These mechanisms enable the release of mRNA into the cytoplasm, initiating the protein translation process.
Given the main target cell of mRNA vaccines are dendritic and other antigen-presenting cells, this stimulates the immune response through the subsequent translation and expression of the mRNA molecule. The translated protein antigens from the mRNA templates prompt the immune system to generate both humoral and cellular responses, whereby the nanocarriers also aid in the sustained release of antigens, prolonging their exposure to immune cells and leading to a robust and prolonged immune reaction.
Safety and Challenges
While nanotechnology offers numerous benefits, safety considerations are paramount. Thorough preclinical and clinical studies are imperative to assess potential toxicities, immunogenicity, and long-term effects of nanocarriers. These investigations contribute to the development of safe and reliable nanotechnology-enhanced mRNA vaccines.
Challenges in this field include fine-tuning the immune response, optimizing nanoparticle biodistribution, and addressing potential adverse events. Collaborative efforts between researchers, clinicians, and regulatory bodies are essential to overcome such challenges and advance the technology.
Future Directions and Applications
Expanding Vaccine Targets
Nanotechnology-enhanced mRNA vaccines hold promise beyond infectious diseases, extending to cancer immunotherapy and personalized medicine. Researchers are exploring ways to utilize these vaccines for a broader range of antigens, including tumour-specific markers, and thus, opening a new avenue of therapeutic arsenal to tackle diseases such as cancer.
Future innovations may involve designing multifunctional nanoparticles that deliver mRNA and possess diagnostic and therapeutic capabilities. Such a combination of therapeutic and diagnostic capabilities is known as theranostics, whereby theranostic nanoparticles could enable real-time monitoring of immune responses as well as provide data on biodistribution and target site distribution, accumulation and retention.
The integration of nanotechnology with mRNA vaccines marks a significant advancement in the field of vaccinology, whereby such a convergence has the potential to reshape disease prevention strategies, offering rapid and tailored solutions to emerging health threats. Continued research, collaboration, and regulatory diligence will be essential to fully unlock the potential of nanotechnology-enhanced mRNA vaccines. As technology evolves, these vaccines may become a cornerstone of modern medicine, offering effective and versatile tools to combat a wide array of diseases.
References and Further Reading
Centers for Disease Control and Prevention (2019) CDC - Nanotechnology - NIOSH Workplace Safety and Health Topic [online]. Centers for Disease Control and Prevention. Available at: https://www.cdc.gov/niosh/topics/nanotech/default.html
Khurana, A. (2021) Role of nanotechnology behind the success of mRNA vaccines for COVID-19. Nano Today [online]. Jun 1;38, p.101142. Available at: https://www.sciencedirect.com/science/article/pii/S1748013221000670
University of Utah Health | University of Utah Health. 2021. mRNA Vaccines for COVID-19 [online]. Available at: https://healthcare.utah.edu/coronavirus/vaccine/mrna-vaccine
Hou, X., et al. (2021) Lipid nanoparticles for mRNA delivery. Nature Reviews Materials [online]. Aug 10;6. Available at: https://www.nature.com/articles/s41578-021-00358-0
Linares-Fernández, S., et al. (2020) Tailoring mRNA Vaccine to Balance Innate/Adaptive Immune Response. Trends in Molecular Medicine [online]. 26(3), pp. 311–23. Available at: https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(19)30244-8
Paliwal, R., et al. (2014) Nanomedicine Scale-up Technologies: Feasibilities and Challenges. AAPS PharmSciTech. Jul 22;15(6), pp.1527–34.
Mirtaleb, M. S., et al. (2023) An insight overview on COVID-19 mRNA vaccines: Advantageous, pharmacology, mechanism of action, and prospective considerations. International Immunopharmacology [online]. Apr 1;117:109934. Available at: https://www.sciencedirect.com/science/article/pii/S1567576923002540
Kheirollahpour, M., et al. (2020) Nanoparticles and Vaccine Development. Pharmaceutical Nanotechnology. Feb 6;8(1), pp. 6–21.
Lee, J., et al. (2023) Knife’s edge: Balancing immunogenicity and reactogenicity in mRNA vaccines. Experimental & Molecular Medicine [online]. Jul 10, pp.1–9. Available at: https://www.nature.com/articles/s12276-023-00999-x
NCI Staff. (2022) How mRNA Vaccines Might Help Treat Cancer - National Cancer Institute [online]. www.cancer.gov. Available from: https://www.cancer.gov/news-events/cancer-currents-blog/2022/mrna-vaccines-to-treat-cancer
MIT Technology Review. What’s next for mRNA vaccines [online]. Available at: https://www.technologyreview.com/2023/01/05/1066274/whats-next-mrna-vaccines/
Pallares, R. M., et al. (2022) Nanoparticle Diagnostics and Theranostics in the Clinic. The Journal of Nuclear Medicine. Oct 27;63(12), pp. 1802–8.