Fast mRNA delivery in vitro and in vivo enabled by magnetic responsive lipid nanoparticles

Abstract Traditional mRNA delivery systems typically require several hours to achieve efficient cellular internalization, and non-internalized mRNA payloads undergo degradation over time. In this study, we develop a fast mRNA delivery platform termed magnetic responsive lipid nanoparticles (MrLNPs) for efficient mRNA delivery. The magnetic responsiveness and enhanced cellular uptake of MrLNPs are confirmed using various LNP-based formulations to deliver diverse mRNA payloads to multiple cell types, demonstrating their broad applicability. Notably, a single administration of MrLNPs enabled fast mRNA delivery and protein expression in mice upon noninvasive magnetic stimulation, achieving a more than 33-fold increase in delivery efficiency compared to conventional non-magnetic LNPs. Overall, this work establishes a novel magnetic responsive mRNA-LNP platform capable of fast mRNA delivery both in vitro and in vivo, with potential applications in acute critical illnesses requiring immediate protein expression.