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 enhance 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.