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Title: Novel cationic cholesterol derivative-based liposomes for serum-enhanced delivery of siRNA. Author: Han SE, Kang H, Shim GY, Suh MS, Kim SJ, Kim JS, Oh YK. Journal: Int J Pharm; 2008 Apr 02; 353(1-2):260-9. PubMed ID: 18178348. 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.[Abstract] [Full Text] [Related] [New Search]