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Anionic amino acid-derived cationic lipid for siRNA delivery
Min Sung Suh, Gayong Shim (*co-first), Han Young Lee, Su-Eun Han, Yong-Hee Yu, Yongseok Choi, Kwangmeyung Kim, Ick Chan Kwon, Kwon Yeon Weon, Young Bong Kim, Yu-Kyoung Oh
Journal of Controlled Release (SCIE)
음이온성 아미노산의 양이온성 유도체를 이용한 siRNA전달연구

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 3β-[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.