Nanotechnology-Based Vaccine Delivery Systems: Current Advances and Emerging Applications
Keywords:
nanotechnology; vaccine delivery; lipid nanoparticles; mRNA vaccines; polymeric nanoparticles; adjuvants; immunization;Abstract
The emergence of nanotechnology has fundamentally transformed the landscape of modern vaccinology, offering unprecedented control over antigen presentation, immune modulation, and targeted delivery. Conventional vaccine platforms, although historically effective, are frequently limited by poor stability, weak immunogenicity of subunit antigens, the requirement for repeated dosing, and dependence on cold-chain logistics. Nanotechnology-based vaccine delivery systems address these limitations by exploiting the unique physicochemical properties of nanoscale materials, including their high surface-area-to-volume ratio, tunable surface chemistry, and capacity to co-encapsulate antigens and immunostimulatory adjuvants. This review provides a comprehensive and critical synthesis of the principal nanocarrier classes currently employed in vaccine development, encompassing lipid nanoparticles, polymeric nanoparticles, inorganic nanoparticles, virus-like particles, and self-assembling protein nanoparticles. Particular attention is devoted to the pivotal role of lipid nanoparticles in enabling the clinical success of messenger RNA (mRNA) vaccines against coronavirus disease 2019, an achievement that has catalysed a global reappraisal of nanocarrier-enabled immunization. The mechanisms by which nanoparticles enhance antigen uptake by antigen-presenting cells, promote lymph node trafficking, and shape the balance between humoral and cellular immunity are examined in detail. Emerging applications, including personalized cancer vaccines, mucosal and needle-free immunization, and pandemic-preparedness platforms, are discussed alongside persistent challenges relating to manufacturing scalability, storage stability, biosafety, and regulatory harmonization. This review highlights the trajectory of the field and identifies the translational hurdles that must be surmounted to realise the full potential of nanotechnology in next-generation vaccines. Collectively, the evidence indicates that rationally engineered nanocarriers will remain central to the development of safe, potent, and broadly deployable vaccines against infectious diseases and cancer.
References
Allahyari, M., & Mohit, E. (2016). Peptide/protein vaccine delivery system based on PLGA particles. Human Vaccines & Immunotherapeutics, 12(3), 806–828.
Bachmann, M. F., & Jennings, G. T. (2010). Vaccine delivery: A matter of size, geometry, kinetics and molecular patterns. Nature Reviews Immunology, 10(11), 787–796.
Buschmann, M. D., Carrasco, M. J., Alishetty, S., Paige, M., Alameh, M. G., & Weissman, D. (2021). Nanomaterial delivery systems for mRNA vaccines. Vaccines, 9(1), 65.
Dolgin, E. (2021). The tangled history of mRNA vaccines. Nature, 597(7876), 318–324.
Dykman, L. A., & Khlebtsov, N. G. (2017). Immunological properties of gold nanoparticles. Chemical Science, 8(3), 1719–1735.
Gao, L., Li, J., & Song, T. (2022). Poly lactic-co-glycolic acid-based nanoparticles as delivery systems for enhanced cancer immunotherapy. Frontiers in Chemistry, 10, 973666.
Han, X., Zhang, H., Butowska, K., Swingle, K. L., Alameh, M. G., Weissman, D., & Mitchell, M. J. (2021). An ionizable lipid toolbox for RNA delivery. Nature Communications, 12(1), 7233.
Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021). Lipid nanoparticles for mRNA delivery. Nature Reviews Materials, 6(12), 1078–1094.
Irvine, D. J., Hanson, M. C., Rakhra, K., & Tokatlian, T. (2015). Synthetic nanoparticles for vaccines and immunotherapy. Chemical Reviews, 115(19), 11109–11146.
Kularatne, R. N., Crist, R. M., & Stern, S. T. (2022). The future of tissue-targeted lipid nanoparticle-mediated nucleic acid delivery. Pharmaceuticals, 15(8), 897.
Marcandalli, J., Fiala, B., Ols, S., Perotti, M., de van der Schueren, W., Snijder, J., … King, N. P. (2019). Induction of potent neutralizing antibody responses by a designed protein nanoparticle vaccine for respiratory syncytial virus. Cell, 176(6), 1420–1431.
Mohsen, M. O., Zha, L., Cabral-Miranda, G., & Bachmann, M. F. (2017). Major findings and recent advances in virus-like particle (VLP)-based vaccines. Seminars in Immunology, 34, 123–132.
Nel, A. E., Mädler, L., Velegol, D., Xia, T., Hoek, E. M. V (2009). Understanding biophysicochemical interactions at the nano-bio interface. Nature Materials, 8(7), 543–557.
Nguyen, B., & Tolia, N. H. (2021). Protein-based antigen presentation platforms for nanoparticle vaccines. npj Vaccines, 6(1), 70.
Pardi, N., Hogan, M. J., Porter, F. W., & Weissman, D. (2018). mRNA vaccines — a new era in vaccinology. Nature Reviews Drug Discovery, 17(4), 261–279.
Reichmuth, A. M., Oberli, M. A., Jaklenec, A., Langer, R., &Blankschtein, D. (2016). mRNA vaccine delivery using lipid nanoparticles. Therapeutic Delivery, 7(5), 319–334.
Rojas, L. A., Sethna, Z., Soares, K. C., Olcese, C., Pang, N., Patterson, E., … Balachandran, V. P. (2021). Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature, 618(7963), 144–150.
Schoenmaker, L., Witzigmann, D., Kulkarni, J. A., Verbeke, R., Kersten, G., Jiskoot, W., & Crommelin, D. J. A. (2021). mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability. International Journal of Pharmaceutics, 601, 120586.
Silva, A. L., Soema, P. C., Slutter, B., Ossendorp, F., &Jiskoot, W. (2016). PLGA particulate delivery systems for subunit vaccines. Human Vaccines & Immunotherapeutics, 12(4), 1056–1069.
Tenchov, R., Bird, R., Curtze, A. E., & Zhou, Q. (2021). Lipid nanoparticles — from liposomes to mRNA vaccine delivery. ACS Nano, 15(11), 16982–17015.
Wang, X., Li, X., Ito, A., Watanabe, Y., Sogo, Y., Hirose, M., … Ohno, T. (2019). Rod-shaped and substituted hydroxyapatite nanoparticles stimulating type 1 and 2 cytokine secretion. Colloids and Surfaces B: Biointerfaces, 174, 26–35.
Zhang, W., Wang, L., Liu, Y., Chen, X., Li, J., & Yang, T. (2019). Chitosan-coated PLGA nanoparticles for nasal delivery of vaccine antigens. European Journal of Pharmaceutics and Biopharmaceutics, 139, 1–10.
Chatzikleanthous, D., O'Hagan, D. T., & Adamo, R. (2021). Lipid-based nanoparticles for delivery of vaccine adjuvants and antigens. Molecular Pharmaceutics, 18(8), 2867–2888.
Gu, P., Wusiman, A., Wang, S., Zhang, Y., Liu, Z., Hu, Y., … Wang, D. (2019). Polyethylenimine-coated PLGA nanoparticles as a vaccine delivery system. Carbohydrate Polymers, 223, 115128.
Kim, J., Eygeris, Y., Gupta, M., & Sahay, G. (2021). Self-assembled mRNA vaccines. Advanced Drug Delivery Reviews, 170, 83–112.
Verbeke, R., Lentacker, I., De Smedt, S. C., &Dewitte, H. (2021). The dawn of mRNA vaccines: The COVID-19 case. Journal of Controlled Release, 333, 511–520.
Butkovich, N., Li, E., Ramirez, A., Burkhardt, A. M., & Wang, S.-W. (2021). Advancements in protein nanoparticle vaccine platforms. WIREs Nanomedicine and Nanobiotechnology, 13(4), e1681.
Curley, S. M., & Putnam, D. (2022). Biological nanoparticles in vaccine development. Frontiers in Bioengineering and Biotechnology, 10, 867119.
Fan, Y., & Moon, J. J. (2015). Nanoparticle drug delivery systems designed to improve cancer vaccines and immunotherapy. Vaccines, 3(3), 662–685.
Al-Halifa, S., Gauthier, L., Arpin, D., Bourgault, S., & Archambault, D. (2019). Nanoparticle-based vaccines against respiratory viruses. Frontiers in Immunology, 10, 22.
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