Chirality-ControlledLipid Nanoparticles for mRNADelivery

mRNA therapeutics present a promising strategy for the treatment of human diseases, which requires a carrier to protect the mRNA and ensure its effective cellular delivery. However, research on how the surface physicochemical properties of the mRNA carriers affect the efficiency of delivery of mRNA into cells has been limited thus far. Here, we report that chirality control of lipid nanoparticles (LNPs) can enhance the delivery and transfection efficiency of cargo mRNA into cells. We prepared chiral LNPs by surface modification of LNPs with chiral cobalt oxide nanoparticles. The chiral LNPs with d- or l-chirality resulted in different cellular uptake and transfection efficiencies of luciferase or EGFP mRNA. Chiral LNPs with d-chirality showed significant enhancement in cellular delivery as well as transfection (5.3-fold) of mRNA compared to the control LNPs. This study suggests a novel strategy of using chirality for the delivery of nucleic acid drugs and provides a more in-depth understanding of the effect of chirality on cells.