Ionizable lipid 4 is a hydrogen peroxide-induced rearrangement product of CA-lipid 5 (pKa = 6.1). It is used in charge-altering lipid nanoparticles (CALNPs) to improve siRNA delivery and gene silencing. LNPs with ionizable lipid 4 and siRNA targeting PLK1 reduce tumor volume in an MCF-7 xenograft model, though less effectively than CALNPs containing CA-lipid 5.
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