Magnetic Lipid Nanoparticles for Targeted mRNA Delivery and Enhanced Organ-Specific Expression

Abstract

Targeted delivery of mRNA therapeutics offers immense potential for improving treatment efficacy while reducing off-target effects. Despite extensive efforts to develop both passive and active targeting strategies, achieving precise and efficient mRNA delivery remains a significant challenge due to rapid clearance, endosomal entrapment, and nonspecific tissue distribution. This study explores magnetic lipid nanoparticles (mLNPs) as an advanced platform for in vivo mRNA delivery. By incorporating an externally applied magnetic field to the heart and lung regions, the impact of mLNPs on the tissue biodistribution and transfection efficiency of luciferase mRNA-loaded mLNPs in mice is examined. While nonmagnetic lipid nanoparticles (nLNPs) or mLNPs without a magnetic field display expected hepatic accumulation, the application of a magnetic field significantly redirects mLNPs to the heart and lungs, as confirmed by increased bioluminescence signals in these tissues. Additionally, reduced bioluminescence is observed in off-target organs such as the liver and spleen. These findings underscore the potential of mLNPs as a precision-targeted delivery system for mRNA therapeutics, enhancing localized gene expression while minimizing systemic exposure. This work contributes to the advancement of next-generation mRNA delivery platforms, offering possibilities for targeted gene therapy and precision medicine.