Suh, Min Sung Shim, Gayong Lee, Han Young Han, Su-Eun Yu, Yong-Hee Choi, Yongseok Kim, Kwangmeyung Kwon, Ick Chan Weon, Kwon Yeon Kim, Young Bong Oh, Yi-Kyoung 2024-01-20T20:03:53Z 2024-01-20T20:03:53Z 2021-09-04 2009-12-16 0168-3659 https://pubs.kist.re.kr/handle/201004/131871 Viable siRNA therapeutic strategies require the concurrent development of effective and safe delivery systems. Here, we described the synthesis of a new cationic lipid, N,N ''-dioleylglutamide (DG), and evaluated DG-based liposomes as an siRNA delivery system. DG, an amino acid derivative, was synthesized by peptide bond linkage of oleylamine to each carboxylic acid group of glutamic acid. Gel retardation assays showed that DG-based cationic liposomes and siRNA began to form complexes from the N/P ratio of 1.8. The viability of A549, HeLa and WM266.4 cells was significantly higher after treatment with DG-based liposomes than with Lipofectamine 2000 and cationic 3 beta-[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol)based liposomes. The DG-based cationic liposomes could effectively deliver a fluorescent model siRNA into A549. HeLa, and WM266.4 human cancer cell lines, showing at least 2-fold higher fluorescence mean intensity values than did Lipofectamine 2000. When survivin-specific siRNA was delivered to cells in lipoplexes, survivin mRNA levels were reduced by DG-based liposomes to the higher extent than Lipofectamine 2000 and DC-Chol-based liposomes. When red fluorescent protein (RFP)-expressing cells were treated with RFP-specific siRNA (siRFP), RFP expression significantly decreased in cells treated with DG-based liposomes. Molecular imaging revealed that intratumoral injection of siRFP and DG-based liposome complexes significantly reduced fluorescence in RFP-expressing tumor tissues in mice. These results suggest that DG-based cationic liposomes would be of value for cellular delivery and in vivo local delivery of siRNA. (C) 2009 Elsevier B.V. All rights reserved. English ELSEVIER SCIENCE BV GENE DELIVERY TRANSFECTION EFFICIENCY RNAI THERAPEUTICS CELLULAR UPTAKE DRUG DISCOVERY PLASMID DNA IN-VITRO LIPOPLEXES LIPOSOMES FORMULATION Anionic amino acid-derived cationic lipid for siRNA delivery Article 10.1016/j.jconrel.2009.06.017 1 JOURNAL OF CONTROLLED RELEASE, v.140, no.3, pp.268 - 276 JOURNAL OF CONTROLLED RELEASE 140 3 268 276 scie scopus 000273081600015 2-s2.0-70450223718 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article; Proceedings Paper GENE DELIVERY TRANSFECTION EFFICIENCY RNAI THERAPEUTICS CELLULAR UPTAKE DRUG DISCOVERY PLASMID DNA IN-VITRO LIPOPLEXES LIPOSOMES FORMULATION Cationic lipid Liposome siRNA Gene reduction Viability