Delivery of small interfering ribonucleic acid using lipid nanoparticles prepared with pH-responsive dipeptide-conjugated lipids.

The development of lipid nanoparticles (LNPs) has enabled the clinical application of small interfering ribonucleic acid (siRNA)-based therapies. Accordingly, various unique ionizable lipids have been explored for efficient siRNA delivery. However, safety concerns related to the structure of ionizable lipids have been raised.

Increasing the siRNA knockdown efficiency of lipid nanoparticles by morphological transformation with the use of dihydrosphingomyelin as a helper lipid.

Lipid nanoparticles (LNPs), comprising ionizable lipids, helper lipids, cholesterol, and PEG lipids, can act as delivery carriers for nucleic acids and have achieved clinical success in the delivery of siRNA and mRNA. It has been shown that the morphology of LNPs varies depending on their lipid composition, but the influence of their morphology on nucleic acid efficacy has not been fully elucidated. In this study, we used our previously developed novel lipid, dioleoylglycerophosphate-diethylenediamine conjugate (DOP-DEDA), to create pH-responsive LNPs (DOP-DEDA LNPs).