Development of a lipoplex-type mRNA carrier composed of an ionizable lipid with a vitamin E scaffold and the KALA peptide for use as an ex vivo dendritic cell-based cancer vaccine

Journal of Controlled Release : Official Journal of the Controlled Release Society
Naho TateshitaHidetaka Akita

Abstract

A dendritic cells (DCs)-based vaccine (DC-vaccine) system is an attractive technology for eliciting antigen-specific immune responses that can protect subjects from infectious diseases and for curing various types of cancers. For the insertion of a foreign antigen to DCs, the transfection of an antigen-coding mRNA to the cells is a promising approach. In order to introduce an antigen, a carrier for mRNA transfection is required, since the mRNA molecule per se is unstable in serum-containing medium. We previously reported on an ionizable lipid-like material with vitamin E-scaffolds (ssPalmE) as a material for a lipid nanoparticle (LNP)-based carrier for nucleic acids. In the present study, we report on the development of a lipoplex-type mRNA carrier for use as a DC-vaccine by using a combination of an ssPalmE-LNP and an α-helical cationic peptide "KALA" (ssPalmE-KALA). The transfection of mRNAs complexed with the ssPalmE-KALA achieved a significantly higher protein expression and the production of proinflammatory cytokines from murine bone marrow derived DCs (BMDCs) in comparison with a lipoplex that was prepared with an ssPalm with fatty acid-scaffolds (myristic acid; ssPalmM-KALA). A cellular uptake process and a pH-responsive...Continue Reading

Citations

Feb 18, 2021·Molecular Cancer·Yang WangXiawei Wei
Dec 11, 2020·Journal of Nanobiotechnology·Amirhossein BahreyniHonglin Luo
Feb 27, 2021·Molecular Cancer·Lei MiaoLeaf Huang
Apr 1, 2021·Bioengineering & Translational Medicine·Michele SchlichPaolo Decuzzi
Jul 20, 2021·Chemical Reviews·Yuebao ZhangYizhou Dong
Aug 23, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Cao Dai PhungJong Oh Kim

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