O12-D3-I3 is an ionizable cationic lipid (pKa = 6.39) that has been used in the generation of lipid nanoparticles (LNPs) for siRNA delivery in vitro and in vivo.1 LNPs containing O12-D3-I3 and encapsulating ferrocene and siRNA targeting nuclear factor erythroid 2-related factor 2 (Nrf2) or the system xc- cystine/glutamate transporter decrease viability of HepG2 hepatocellular carcinoma cells. LNPs containing O12-D3-I3 and an mRNA reporter selectively accumulate in the tumor and liver over the lungs, kidneys, spleen, and heart in an MCF-7 breast cancer mouse xenograft model. LNPs containing O12-D3-I3 and encapsulating ferrocene and either Nrf2-targeting siRNA or system xc- cystine/glutamate transporter-targeting siRNA reduce tumor growth and volume in an MCF-7 mouse xenograft model. LNPs containing O12-D3-I3 and encapsulating siRNA targeting Factor VII decrease hepatocyte Factor VII mRNA levels in mice.
References:
[1]. Liu, Y., He, F., Chen, L., et al.Imidazolyl lipids enhanced LNP endosomal escape for ferroptosis RNAi treatment of cancerSmall20(40)e2402362(2024).