Combination of ionizable lipids with oleic acid and vitamin E scaffolds for RNA cancer vaccine delivery

🥉 Top 5% JournalNov 19, 2025Journal of controlled release : official journal of the Controlled Release Society

Using special fats with oleic acid and vitamin E to deliver RNA cancer vaccines

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Abstract

The inclusion of vitamin E moieties in lipid nanoparticles significantly enhanced cellular immune responses and suppressed tumor growth in a mouse model.

Lipid nanoparticles containing a combination of ionizable lipids were developed to improve vaccine efficacy.
The formulation showed enhanced capability to induce cellular immunity in tumor-bearing mice.
Robust activation of reactive CD8 T cells was observed, specifically recognizing neoantigens expressed in gastric cells.
Tumor suppression was demonstrated in the YTN16 tumor model using the developed lipid nanoparticles.
Lipid nanoparticles may serve as a viable platform for RNA-based cancer vaccines.

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RNA vaccines based on lipid nanoparticles (LNPs) encapsulating in vitro transcribed mRNA (IVT-mRNA) are a successful but evolving vaccine modality. It has been increasingly recognized that LNPs, which are mainly composed of ionizable lipids, have two roles in the action of RNA vaccines: delivering mRNA into the cytoplasm by overcoming the endosomal membrane and stimulating the innate immune system as an adjuvant. In this study, we report the development of LNPs with enhanced capability to induce cellular immunity by using a combination of ionizable lipids: one containing an oleic scaffold with high transfection activity (ssPalmO-Phe; SS-OP) and the other containing a vitamin E scaffold with high adjuvant activity (ssPalmE; SS-EC), referred to as LNP. The formulation's efficacy was evaluated in tumor-bearing mice, focusing on immune responses and tumor suppression. The results showed that the inclusion of vitamin E moieties in LNPsignificantly enhanced cellular immune responses and suppressed tumor growth in an E.G7-OVA tumor-bearing mouse model. Additionally, it demonstrated robust activation of reactive CD8T cells specifically recognizing the neoantigens mCdt1, mScarb2, and mZfp106, which are expressed in YTN16 murine gastric cells. Suppression of YTN16 tumors was also observed using LNP. The study suggests that LNPis a viable platform for RNA-based cancer vaccines, offering a potent combination of gene expression and immune stimulation. OP/EC OP/EC OP/EC OP/EC +

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