The optimization strategies of LNP-mRNA formulations: Development and challenges for further application

Since the successful development and application of the COVID-19 mRNA vaccine, lipid nanoparticle (LNP)-based nucleic acid delivery therapy has received much attention, and the technology is increasingly mature, gradually becomes an innovative means to treat various diseases. Although the LNP-mRNA therapy has become an effective treatment, several challenges still remained for clinical application. In this review, we first briefly introduced the development of LNPs, including its preparation. Subsequently, based on previous studies of LNP-mRNA formulations, we discussed the effects of components on the physicochemical characteristics, such as size, zeta potential, stability, storage conditions, and encapsulation efficiency. Then, relationships between components and their in vivo performance were discussed, including targeting ability, endosomal escape, and transfection. Furthermore, we summarized the modification/optimization strategies of LNP-mRNA formulations for reducing toxicity. Finally, the development of mRNA therapy based on LNPs has prospected, and some suggestions for LNP formulations and optimization were put forward.