title: Novel cationic cholesterol derivative-based liposomes for serum-enhanced delivery of siRNA.
abstract: Most cationic liposomes used for gene delivery suffer from reduced transfection efficiency in the presence of serum. In this study, we report serum-enhanced delivery efficiency of siRNA via the use of newly synthesized liposomes that contain cationic lipids. Two cholesterol derivatives, cholesteryloxypropan-1-amine (COPA) and cholesteryl-2-aminoethylcarbamate (CAEC), were synthesized. A fluorescein label was then used to visualize cellular uptake of small interfering RNA (siRNA) via COPA or CAEC-based liposomes. The presence of serum had different effects on the cellular delivery of siRNA when siRNA was complexed to different cationic liposomes. CAEC-based liposomes showed significantly reduced cellular delivery of siRNA in serum-containing media as compared to serum-free media. Conversely, COPA-based liposomes (COPA-L) provided serum-enhanced delivery of siRNA in Hepa1-6, A549, and Hela cell lines. Following delivery of the oncogene survivin-specific siRNA, COPA-L reduced the mRNA expression levels of the target gene more efficiently than did Lipofectamine 2000. The delivery of green fluorescent protein-specific siRNA with COPA-L reduced the expression of green fluorescent protein in 293T stable cell lines. The apoptosis of Hepa1-6 significantly increased by delivery of survivin-specific siRNA by COPA-L. Additionally, Hepa1-6, A549, and Hela cells were >80% viable after treatment with COPA-L. These results suggest that the newly synthesized cholesterol derivative, COPA-L, could be further developed as a serum-enhanced delivery system of siRNA.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seungbuk-Gu, Seoul, South Korea.
authors.forename: Su-Eun
authors.initials: SE
authors.lastname: Han
authors.forename: Hyungu
authors.initials: H
authors.lastname: Kang
authors.forename: Ga Yong
authors.initials: GY
authors.lastname: Shim
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Suh
authors.forename: Sun Jae
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Kim
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D044967:Serum; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008081:Liposomes; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; D002784:Cholesterol