Zeolitic Imidazolate Frameworks Enhanced Transfection Efficiency of mRNA Loaded Lipid Nanoparticles.

Abstract

mRNA vaccines have emerged as a highly effective strategy for the prevention and treatment of various diseases. A critical factor driving the success of mRNA vaccines is the development of advanced multicomponent lipid nanoparticles (LNPs) as a delivery system. As mRNA-LNP technology becomes increasingly integral to vaccine and therapeutic development, there is significant potential to enhance LNP efficiency and build upon the first generation of clinically approved mRNA-LNP products. This can lead to the development of superior formulations that achieve higher protein expression and improved therapeutic outcomes. In this study, we present a novel approach to enhancing the transfection efficiency of mRNA-LNPs using ZIF-8 metal-organic framework (MOF). We demonstrate effective encapsulation of mRNA-LNPs within ZIF-8, with preserved structural integrity during dissociation and release. Remarkably, following MOF encapsulation and release, we observed a 3-fold and 8-fold increase in transfection efficiency of the mRNA-LNPs at 48 h in HEK-293 and HCT-116 cells, respectively. Our findings suggest that the presence of ZIF-8 materials with the mRNA-LNPs significantly contributes to their improved transfection and translation efficiency.