Biodegradable hyperbranched poly(amine-co-ester)-based polymeric nanoparticles for mRNA delivery

Abstract

AbstractDespite the availability of mRNA vaccines utilizing LNP delivery technology, there remains a pressing need for the development of non-viral mRNA delivery vectors that are both more efficient and safe. we present a novel hyperbranched poly(amine-co-ester) (HBPA) system, catalyzed by immobilized lipase, for efficientin vitroandin vivomRNA delivery. By polymerizing four monomers, we successfully synthesized HBPA with a hyperbranched structure, and subsequent modification of the end groups resulted in HBPA-E. Comparative evaluations revealed that HBPA-E outperforms linear PACE and the commercial transfection reagent Lipofectamine MessengerMAX (LipoMM) in terms of intracellular delivery efficiency, while demonstrating lower cytotoxicity. Furthermore, thein vivopulmonary delivery efficiency of HBPA-E was significantly superior to that of LPA-E and the commercialin vivodelivery reagent in vivo-JetRNA. Finally, the HBPA-E can be easily dissolved in ethanol, and its mRNA formulation can be employed as a freeze-drying formulation, making it a valuable candidate for future clinical applications of mRNA delivery.