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Adv. Sci., 30 January 2025 | https://doi.org/10.1002/advs.202407383
Muco-Penetrating Lipid Nanoparticles Having a Liquid Core for Enhanced Intranasal mRNA Delivery
Nipuni Maniyamgama 1,†, Ki Hyun Bae 1,†, Zi Wei Chang 2, Jialing Lee 1, Melgious J. Y. Ang 1, Yong Jie Tan 2, Lisa F. P. Ng 2, Laurent Renia 2,3,4, Kevin P. White 5, and Yi Yan Yang 1,*
1Bioprocessing Technology Institute (BTI)Agency for Science, Technology and Research (A*STAR)20 Biopolis Way, Centros #06-01, Singapore 138668, Republic of Singapore
2A*STAR Infectious Diseases Labs (A*STAR ID Labs)Agency for Science, Technology and Research (A*STAR)8A Biomedical Grove, Immunos #05-13, Singapore 138648, Republic of Singapore
3Lee Kong Chian School of Medicine Nanyang Technological University Singapore 138648, Republic of Singapore
4School of Biological Sciences Nanyang Technological University Singapore 138648, Republic of Singapore
5Department of Biochemistry and Precision Medicine Translational Research Program Yong Loo Lin School of Medicine National University of Singapore Singapore 119228, Republic of Singapore
†These authors contributed equally
*Corresponding author: correspondence to Yi Yan Yang
*Corresponding author: correspondence to Yi Yan Yang
Abstract
Intranasal delivery of mRNA vaccines offers promising opportunities to combat airborne viruses like SARS-CoV-2 by provoking mucosal immunity, which not only defends against respiratory infection but also prevents contagious transmission. However, the development of nasal mRNA vaccines has been hampered by the lack of effective means to overcome the mucus barrier. Herein, ionizable lipid-incorporated liquid lipid nanoparticles (iLLNs) capable of delivering mRNA cargo across airway mucosa are designed. Adjusting the ratios of ionizable and cationic lipids allows fine-tuning of the pKa of iLLNs to the range of nasal mucosal pH (5.5–6.5), thus facilitating mucus penetration via the formation of near-neutral, PEGylated muco-inert surfaces. When nasally administered to mice, the top candidate iLLN-2/mRNA complexes enable about 60-fold greater reporter gene expression in the nasal cavity, compared to the benchmark mRNA-lipid nanoparticles (ALC-LNP) having the same lipid composition as that of BNT162b2 vaccine. Moreover, a prime-boost intranasal immunization of iLLN-2/mRNA complexes elicits a greater magnitude of SARS-CoV-2 spike-specific mucosal IgA and IgG response than ALC-LNP, without triggering any noticeable inflammatory reactions. Taken together, these results provide useful insights for the design of nasally deliverable mRNA formulations for prophylactic applications.
논문정보
- Research article
- 2025년 01월 (BRIC 등록일 2025-01-31)
- 국외 연구진
- 바이오·의료융합 > 바이오소재
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