A University of Pennsylvania team has demonstrated that modifying the ionizable lipid component of lipid nanoparticles (LNPs) by adding phenol groups can both reduce inflammatory side effects and improve mRNA delivery efficiency. Utilizing the Mannich reaction to synthesize a library of new lipids, researchers identified antioxidant ionizable lipids that mitigate oxidative stress, resulting in enhanced therapeutic profiles. These findings, published in Nature Biomedical Engineering, represent a significant step toward safer and more potent mRNA-based therapies and vaccines.