Cationic liposomes containing a cationic lipid, such as 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), have often been used for the transduction of plasmid DNA (pDNA) . However, such liposomes induce gene expression primarily in the lungs after intravenous injection. To improve the delivery of cationic liposomes/pDNA complexes (pDNA lipoplexes) to the liver by intravenous administration, the current study synthesized two apolipoprotein E (ApoE)-derived peptides, dApoE-R9 and ApoE-F-R9, for liver targeting via certain ApoE receptors, including the low-density lipoprotein receptor. Ternary complexes of pDNA, cationic liposomes and ApoE-R9 peptide were also prepared. After transfection, ternary complexes with DOTAP/1,2-dioleoyl--glycero-3-phosphoethanolamine (DOPE) liposomes exhibited high transfection activity in HepG2 cells compared with DOTAP/cholesterol (Chol) liposomes. In particular, ternary complexes with dApoE-R9 exhibited high transfection activity in cells compared with ApoE-F-R9. However, transfection studies revealed that ternary complexes with DOTAP/DOPE liposomes and dApoE-R9 did not increase gene expression in the liver compared with DOTAP/DOPE lipoplexes. In contrast, ternary complexes with DOTAP/Chol liposomes and dApoE-R9 increased gene expression in the liver compared with DOTAP/Chol lipoplexes. The results demonstrated that the optimal liposomal formulation in ternary complexes with ApoE-R9 peptide for liver delivery were different from those that were .
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| http://dx.doi.org/10.3892/etm.2019.7863 | DOI Listing |
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