Lipid Nanoparticle Chaperone with Redox-Adaptive Intracellular Microenvironment Modulation Potentiates the Potency of mRNA Vaccines

Vitamin E significantly enhances mRNA translation efficiency and antigen presentation by dendritic cells.

• High levels of reactive oxygen species, like hydrogen peroxide, can hinder mRNA translation and antigen presentation.
• Vitamin E was identified as an effective antioxidant that improves the performance of lipid nanoparticles in mRNA delivery.
• A novel vitamin E-modified lipid was designed to release vitamin E in response to elevated hydrogen peroxide levels during transfection.
• The incorporation of this modified lipid into lipid nanoparticles enhances intracellular redox balance and translation efficiency.
• mRNA vaccines using this delivery system demonstrated strong antitumor immune responses and reduced tumor growth in multiple cancer models.

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