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Delivery of mRNA Vaccine with 1, 2-Diesters-Derived Lipids Elicits Fast Liver Clearance for Safe and Effective Cancer Immunotherapy.
- Source :
-
Advanced healthcare materials [Adv Healthc Mater] 2024 Feb; Vol. 13 (5), pp. e2302691. Date of Electronic Publication: 2023 Nov 29. - Publication Year :
- 2024
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Abstract
- Messenger RNA (mRNA) vaccine is explored as a promising strategy for cancer immunotherapy, but the side effects, especially the liver-related damage caused by LNP, raise concerns about its safety. In this study, a novel library of 248 ionizable lipids comprising 1,2-diesters is designed via a two-step process involving the epoxide ring-opening reaction with carboxyl group-containing alkyl chains followed by an esterification reaction with the tertiary amines. Owing to the special chemical structure of 1,2-diesters, the top-performing lipids and formulations exhibit a faster clearance rate in the liver, contributing to increased stability and higher safety compared with DLin-MC3-DMA. Moreover, the LNP shows superior intramuscular mRNA delivery and elicits robust antigen-specific immune activation. The vaccinations delivered by the LNP system suppress tumor growth and prolong survival in both model human papillomavirus E7 and ovalbumin antigen-expressing tumor models. Finally, the structure of lipids which enhances the protein expression in the spleen and draining lymph nodes compared with ALC-0315 lipid in Comirnaty is further optimized. In conclusion, the 1, 2-diester-derived lipids exhibit rapid liver clearance and effective anticancer efficiency to different types of antigens-expressing tumor models, which may be a safe and universal platform for mRNA vaccines.<br /> (© 2023 Wiley-VCH GmbH.)
Details
- Language :
- English
- ISSN :
- 2192-2659
- Volume :
- 13
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Advanced healthcare materials
- Publication Type :
- Academic Journal
- Accession number :
- 37990414
- Full Text :
- https://doi.org/10.1002/adhm.202302691