Volume 13, Issue 2 (6-2025)                   JoMMID 2025, 13(2): 88-96 | Back to browse issues page

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Mohebbi S, Ghanbari M, Baesi K. Nanoplatform-Based Delivery Systems for Enhanced Stability and Efficacy of Nucleic Acid Vaccines. JoMMID 2025; 13 (2) :88-96
URL: http://jommid.pasteur.ac.ir/article-1-764-en.html
Nanoplatform-Based Delivery Systems for Enhanced Stability and Efficacy of Nucleic Acid Vaccines
Sohameh Mohebbi , Maryam Ghanbari * , Kazem Baesi
Department of Microbial Biotechnology, Faculty of Biological Science, Tehran North Branch, Islamic Azad University, Tehran, Iran
Abstract:   (101 Views)
The rapid development of nucleic acid-based vaccines represents a major advancement in immunization strategies, characterized by their reliance on host cellular machinery to produce antigens. These third-generation platforms, including DNA and mRNA vaccines, offer key advantages such as rapid scalability, simplified manufacturing, and versatility in targeting a broad spectrum of diseases caused by infectious pathogens or conditions like cancer. While they avoid the use of live pathogens and thereby minimize many infection-related risks associated with pathogen reversion, potential side effects such as immune overactivation or off-target responses remain key safety considerations. Nanotechnology, particularly lipid nanoparticle (LNP) systems, has emerged as a critical enabler in addressing these limitations. LNPs enhance nucleic acid stability, promote cellular uptake, and facilitate targeted delivery, thereby improving both immune activation and overall safety profiles. Innovations in ionizable lipid design, PEGylation, and size-controlled formulations have been pivotal to the success of mRNA vaccines in response to the COVID-19 pandemic. This review focuses primarily on LNPs as delivery platforms, while also discussing emerging nanotechnologies under investigation in both preclinical and clinical settings. By examining advances in nanoparticle engineering, delivery strategies, and disease-specific applications, this review aims to provide a comprehensive overview of how nanotechnology is reshaping the future of nucleic acid vaccine development. This underscores the transformative potential of nanoscale delivery systems in overcoming current barriers and accelerating the innovation of next-generation vaccines.
Keywords: Nucleic acid vaccines, Lipid nanoparticles (LNPs), Vaccine stability, Vaccine delivery, Adjuvants, mRNA vaccines, Nanotechnology
Full-Text [PDF 978 kb]   (12 Downloads)    
Type of Study: Review article | Subject: Immune responses, deficiencies and vaccine candidates
Received: 2025/08/9 | Accepted: 2025/06/11 | Published: 2025/06/11
References
1. Rappuoli R, Black S, Lambert PH. Vaccine discovery and translation of new vaccine technology. Lancet. 2011; 378 (9788): 360-8. [DOI:10.1016/S0140-6736(11)60440-6] [PMID]
2. Koff WC, Burton DR, Johnson PR, Walker BD, King CR, Nabel GJ, et al. Accelerating next-generation vaccine development for global disease prevention. Science. 2013; 340 (6136): 1232910. [DOI:10.1126/science.1232910] [PMID] [PMCID]
3. Wadhwa A, Aljabbari A, Lokras A, Foged C, Thakur A. Opportunities and challenges in the delivery of mRNA-based vaccines. Pharmaceutics. 2020; 12 (2): 102. [DOI:10.3390/pharmaceutics12020102] [PMID] [PMCID]
4. Cid R, Bolívar J. Platforms for production of protein-based vaccines: from classical to next-generation strategies. Biomolecules. 2021; 11 (8): 1072. [DOI:10.3390/biom11081072] [PMID] [PMCID]
5. Excler JL, Saville M, Berkley S, Kim JH. Vaccine development for emerging infectious diseases. Nat Med. 2021; 27 (4): 591-600. [DOI:10.1038/s41591-021-01301-0] [PMID]
6. Fang E, Liu X, Li M, Zhang Z, Song L, Zhu B, et al. Advances in COVID-19 mRNA vaccine development. Signal Transduct Target Ther. 2022; 7 (1): 94. [DOI:10.1038/s41392-022-00950-y] [PMID] [PMCID]
7. Qin F, Xia F, Chen H, Cui B, Feng Y, Zhang P, et al. A guide to nucleic acid vaccines in the prevention and treatment of infectious diseases and cancers: from basic principles to current applications. Front Cell Dev Biol. 2021; 9: 633776. [DOI:10.3389/fcell.2021.633776] [PMID] [PMCID]
8. Lu B, Lim JM, Yu B, Song S, Neeli P, Sobhani N, et al. The next-generation DNA vaccine platforms and delivery systems: advances, challenges and prospects. Front Immunol. 2024; 15: 1332939. [DOI:10.3389/fimmu.2024.1332939] [PMID] [PMCID]
9. Brisse M, Vrba SM, Kirk N, Liang Y, Ly H. Emerging concepts and technologies in vaccine development. Front Immunol. 2020; 11: 583077. [DOI:10.3389/fimmu.2020.583077] [PMID] [PMCID]
10. Wang S, Lu S. DNA immunization. Curr Protoc Microbiol. 2013; 31 (1): 18.3.1-18.3.24. [DOI:10.1002/9780471729259.mc1803s31] [PMID] [PMCID]
11. Williams JA. Vector design for improved DNA vaccine efficacy, safety and production. Vaccines. 2013; 1 (3): 225-49. [DOI:10.3390/vaccines1030225] [PMID] [PMCID]
12. Rosa SS, Prazeres DMF, Azevedo AM, Marques MPC. mRNA vaccines manufacturing: challenges and bottlenecks. Vaccine. 2021; 39 (16): 2190-200. [DOI:10.1016/j.vaccine.2021.03.038] [PMID] [PMCID]
13. Leppek K, Byeon GW, Kladwang W, Wayment-Steele HK, Kerr CH, Xu AF, et al. Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics. Nat Commun. 2022; 13 (1): 1536. [DOI:10.1038/s41467-022-28776-w] [PMID] [PMCID]
14. Jin L, Zhou Y, Zhang S, Chen SJ. mRNA vaccine sequence and structure design and optimization: advances and challenges. J Biol Chem. 2025; 301 (1): 108015. [DOI:10.1016/j.jbc.2024.108015] [PMID] [PMCID]
15. Pardi N, Parkhouse K, Kirkpatrick E, McMahon M, Zost SJ, Mui BL, et al. Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies. Nat Commun. 2018; 9 (1): 3361. [DOI:10.1038/s41467-018-05482-0] [PMID] [PMCID]
16. Maruggi G, Zhang C, Li J, Ulmer JB, Yu D. mRNA as a transformative technology for vaccine development to control infectious diseases. Mol Ther. 2019; 27 (4): 757-72. [DOI:10.1016/j.ymthe.2019.01.020] [PMID] [PMCID]
17. Kutzler MA, Weiner DB. DNA vaccines: ready for prime time? Nat Rev Genet. 2008; 9 (10): 776-88. [DOI:10.1038/nrg2432] [PMID] [PMCID]
18. Liang Y, Huang L, Liu T. Development and delivery systems of mRNA vaccines. Front Bioeng Biotechnol. 2021; 9: 718753. [DOI:10.3389/fbioe.2021.718753] [PMID] [PMCID]
19. Yang B, Jeang J, Yang A, Wu TC, Hung CF. DNA vaccine for cancer immunotherapy. Hum Vaccin Immunother. 2014; 10 (11): 3153-64. [DOI:10.4161/21645515.2014.980686] [PMID] [PMCID]
20. Liu MA. DNA vaccines: an historical perspective and view to the future. Immunol Rev. 2011; 239 (1): 62-84. [DOI:10.1111/j.1600-065X.2010.00980.x] [PMID]
21. Schlake T, Thess A, Fotin-Mleczek M, Kallen KJ. Developing mRNA-vaccine technologies. RNA Biol. 2012; 9 (11): 1319-30. [DOI:10.4161/rna.22269] [PMID] [PMCID]
22. Li L, Petrovsky N. Molecular mechanisms for enhanced DNA vaccine immunogenicity. Expert Rev Vaccines. 2016; 15 (3): 313-29. [DOI:10.1586/14760584.2016.1124762] [PMID] [PMCID]
23. Rauch S, Lutz J, Kowalczyk A, Schlake T, Heidenreich R. RNActive technology: generation and testing of stable and immunogenic mRNA vaccines. In: Rabinovich PM, editor. Synthetic messenger RNA and cell metabolism modulation: methods and protocols. New York: Humana Press; 2017. p. 89-107. [DOI:10.1007/978-1-4939-6481-9_5] [PMID]
24. Pandya A, Shah Y, Kothari N, Postwala H, Shah A, Parekh P, et al. The future of cancer immunotherapy: DNA vaccines leading the way. Med Oncol. 2023; 40 (7): 200. [DOI:10.1007/s12032-023-02060-3] [PMID] [PMCID]
25. Ulmer JB, Mason PW, Geall A, Mandl CW. RNA-based vaccines. Vaccine. 2012; 30 (30): 4414-8. [DOI:10.1016/j.vaccine.2012.04.060] [PMID]
26. Dobrovolskaia MA, McNeil SE. Immunological and hematological toxicities challenging clinical translation of nucleic acid-based therapeutics. Expert Opin Biol Ther. 2015; 15 (7): 1023-48. [DOI:10.1517/14712598.2015.1014794] [PMID]
27. Würtele H, Little KCE, Chartrand P. Illegitimate DNA integration in mammalian cells. Gene Ther. 2003; 10 (21): 1791-9. [DOI:10.1038/sj.gt.3302074] [PMID]
28. Gote V, Bolla PK, Kommineni N, Butreddy A, Nukala PK, Palakurthi SS, et al. A comprehensive review of mRNA vaccines. Int J Mol Sci. 2023; 24 (3): 2700. [DOI:10.3390/ijms24032700] [PMID] [PMCID]
29. Jiang Y, Rubin L, Peng T, Liu L, Xing X, Lazarovici P, et al. Cytokine storm in COVID-19: from viral infection to immune responses, diagnosis and therapy. Int J Biol Sci. 2022; 18 (2): 459. [DOI:10.7150/ijbs.59272] [PMID] [PMCID]
30. Rizvi SA, Saleh AM. Applications of nanoparticle systems in drug delivery technology. Saudi Pharm J. 2018; 26 (1): 64-70. [DOI:10.1016/j.jsps.2017.10.012] [PMID] [PMCID]
31. Pati R, Shevtsov M, Sonawane A. Nanoparticle vaccines against infectious diseases. Front Immunol. 2018; 9: 2224. [DOI:10.3389/fimmu.2018.02224] [PMID] [PMCID]
32. Maier MA, Jayaraman M, Matsuda S, Liu J, Barros S, Querbes W, et al. Biodegradable lipids enabling rapidly eliminated lipid nanoparticles for systemic delivery of RNAi therapeutics. Mol Ther. 2013; 21 (8): 1570-8. [DOI:10.1038/mt.2013.124] [PMID] [PMCID]
33. Khare P, Dave KM, Kamte YS, Manoharan MA, O'Donnell LA, Manickam DS. Development of lipidoid nanoparticles for siRNA delivery to neural cells. AAPS J. 2021; 24 (1): 8. [DOI:10.1208/s12248-021-00653-2] [PMID] [PMCID]
34. Kulkarni JA, Witzigmann D, Leung J, Tam YYC, Cullis PR. On the role of helper lipids in lipid nanoparticle formulations of siRNA. Nanoscale. 2019; 11 (45): 21733-9. [DOI:10.1039/C9NR09347H] [PMID]
35. Adams D, Gonzalez-Duarte A, O'Riordan WD, Yang CC, Ueda M, Kristen AV, et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med. 2018; 379 (1): 11-21. [DOI:10.1056/NEJMoa1716153] [PMID]
36. Hou X, Zaks T, Langer R, Dong Y. Lipid nanoparticles for mRNA delivery. Nat Rev Mater. 2021; 6 (12): 1078-94. [DOI:10.1038/s41578-021-00358-0] [PMID] [PMCID]
37. Barenholz Y. Doxil®-The first FDA-approved nano-drug: Lessons learned. J Control Release. 2012; 160 (2): 117-34. [DOI:10.1016/j.jconrel.2012.03.020] [PMID]
38. Kim EM, Jeong HJ. Liposomes: biomedical applications. Chonnam Med J. 2021; 57 (1): 27-35. [DOI:10.4068/cmj.2021.57.1.27] [PMID] [PMCID]
39. Gu W, Andrews GP, Tian Y. Recent clinical successes in liposomal nanomedicines. Int J Drug Discov Pharmacol. 2023; 2 (1): 52-9. [DOI:10.53941/ijddp.0201009]
40. Viegas C, Patrício AB, Prata JM, Nadhman A, Chintamaneni PK, Fonte P. Solid lipid nanoparticles vs. nanostructured lipid carriers: a comparative review. Pharmaceutics. 2023; 15 (6): 1593. [DOI:10.3390/pharmaceutics15061593] [PMID] [PMCID]
41. Riccardi D, Baldino L, Reverchon E. Liposomes, transfersomes and niosomes: production methods and their applications in the vaccinal field. J Transl Med. 2024; 22 (1): 339. [DOI:10.1186/s12967-024-05160-4] [PMID] [PMCID]
42. Ferraresso F, Strilchuk AW, Juang LJ, Poole LG, Luyendyk JP, Kastrup CJ. Comparison of DLin-MC3-DMA and ALC-0315 for siRNA delivery to hepatocytes and hepatic stellate cells. Mol Pharm. 2022; 19 (7): 2175-82. [DOI:10.1021/acs.molpharmaceut.2c00033] [PMID] [PMCID]
43. Schlich M, Palomba R, Costabile G, Mizrahy S, Pannuzzo M, Peer D, et al. Cytosolic delivery of nucleic acids: The case of ionizable lipid nanoparticles. Bioeng Transl Med. 2021; 6 (2): e10213. [DOI:10.1002/btm2.10213] [PMID] [PMCID]
44. Semple SC, Akinc A, Chen J, Sandhu AP, Mui BL, Cho CK, et al. Rational design of cationic lipids for siRNA delivery. Nat Biotechnol. 2010; 28 (2): 172-6. [DOI:10.1038/nbt.1602] [PMID]
45. Guimaraes LC, Costa PAC, Scalzo Júnior SRA, Ferreira HAS, Braga ACS, de Oliveira LC, et al. Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models. Nat Commun. 2024; 15 (1): 590. [DOI:10.1038/s41467-024-44830-1] [PMID] [PMCID]
46. Tenchov R, Sasso JM, Zhou QA. PEGylated lipid nanoparticle formulations: immunological safety and efficiency perspective. Bioconjug Chem. 2023; 34 (6): 941-60. [DOI:10.1021/acs.bioconjchem.3c00174] [PMID] [PMCID]
47. Ly HH, Daniel S, Soriano SK, Kis Z, Blakney AK. Optimization of lipid nanoparticles for saRNA expression and cellular activation using a design-of-experiment approach. Mol Pharm. 2022; 19 (6): 1892-905. [DOI:10.1021/acs.molpharmaceut.2c00032] [PMID] [PMCID]
48. Farooq MA, Johnston AP, Trevaskis NL. Impact of nanoparticle properties on immune cell interactions in the lymph node. Acta Biomater. 2025: 193: 65-82. [DOI:10.1016/j.actbio.2024.12.039] [PMID]
49. Catenacci L, Rossi R, Sechi F, Buonocore D, Sorrenti M, Perteghella S, et al. Effect of lipid nanoparticle physico-chemical properties and composition on their interaction with the immune system. Pharmaceutics. 2024; 16 (12): 1521. [DOI:10.3390/pharmaceutics16121521] [PMID] [PMCID]
50. Sahin U, Karikó K, Türeci Ö. mRNA-based therapeutics-developing a new class of drugs. Nat Rev Drug Discov. 2014; 13 (10): 759-80. [DOI:10.1038/nrd4278] [PMID]
51. Tang Y, Liu B, Zhang Y, Liu Y, Huang Y, Fan W. Interactions between nanoparticles and lymphatic systems: Mechanisms and applications in drug delivery. Adv Drug Deliv Rev. 2024; 209: 115304. [DOI:10.1016/j.addr.2024.115304] [PMID]
52. Baranov MV, Kumar M, Sacanna S, Thutupalli S, van den Bogaart G. Modulation of immune responses by particle size and shape. Front Immunol. 2021; 11: 607945. [DOI:10.3389/fimmu.2020.607945] [PMID] [PMCID]
53. Sasaki K, Sato Y, Okuda K, Iwakawa K, Harashima H. mRNA-loaded lipid nanoparticles targeting dendritic cells for cancer immunotherapy. Pharmaceutics. 2022; 14 (8): 1572. [DOI:10.3390/pharmaceutics14081572] [PMID] [PMCID]
54. Cullis PR, Hope MJ. Lipid nanoparticle systems for enabling gene therapies. Mol Ther. 2017; 25 (7): 1467-75. [DOI:10.1016/j.ymthe.2017.03.013] [PMID] [PMCID]
55. Love KT, Mahon KP, Levins CG, Whitehead KA, Querbes W, Dorkin JR, et al. Lipid-like materials for low-dose, in vivo gene silencing. Proc Natl Acad Sci U S A. 2010; 107 (5): 1864-9. [DOI:10.1073/pnas.0910603106] [PMID] [PMCID]
56. Yuan Z, Yan R, Fu Z, Wu T, Ren C. Impact of physicochemical properties on biological effects of lipid nanoparticles: Are they completely safe. Sci Total Environ. 2024; 927: 172240. [DOI:10.1016/j.scitotenv.2024.172240] [PMID]
57. Lorenzer C, Dirin M, Winkler AM, Baumann V, Winkler J. Going beyond the liver: progress and challenges of targeted delivery of siRNA therapeutics. J Control Release. 2015; 203: 1-15. [DOI:10.1016/j.jconrel.2015.02.003] [PMID]
58. Di J, Du Z, Wu K, Jin S, Wang X, Li T, et al. Biodistribution and non-linear gene expression of mRNA LNPs affected by delivery route and particle size. Pharm Res. 2022; 39 (1): 105-14. [DOI:10.1007/s11095-022-03166-5] [PMID] [PMCID]
59. Witzigmann D, Kulkarni JA, Leung J, Chen S, Cullis PR, van der Meel R. Lipid nanoparticle technology for therapeutic gene regulation in the liver. Adv Drug Deliv Rev. 2020; 159: 344-63. [DOI:10.1016/j.addr.2020.06.026] [PMID] [PMCID]
60. Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines - a new era in vaccinology. Nat Rev Drug Discov. 2018; 17 (4): 261-79. [DOI:10.1038/nrd.2017.243] [PMID] [PMCID]
61. Samaridou E, Heyes J, Lutwyche P. Lipid nanoparticles for nucleic acid delivery: Current perspectives. Adv Drug Deliv Rev. 2020; 154-155: 37-63. [DOI:10.1016/j.addr.2020.06.002] [PMID]
62. Suzuki Y, Ishihara H. Difference in the lipid nanoparticle technology employed in three approved siRNA (Patisiran) and mRNA (COVID-19 vaccine) drugs. Drug Metab Pharmacokinet. 2021; 41: 100424. [DOI:10.1016/j.dmpk.2021.100424] [PMID] [PMCID]
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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.