title: Efficient delivery of Notch1 siRNA to SKOV3 cells by cationic cholesterol derivative-based liposome.
abstract: A novel cationic cholesterol derivative-based small interfering RNA (siRNA) interference strategy was suggested to inhibit Notch1 activation in SKOV3 cells for the gene therapy of ovarian cancer. The cationic cholesterol derivative,N-(cholesterylhemisuccinoyl-amino-3-propyl)-N,N-dimethylamine (DMAPA-chems) liposome, was incubated with siRNA at different nitrogen-to-phosphate ratios to form stabilized, near-spherical siRNA/DMAPA-chems nanoparticles with sizes of 100-200 nm and zeta potentials of 40-50 mV. The siRNA/DMAPA-chems nanoparticles protected siRNA from nuclease degradation in 25% fetal bovine serum. The nanoparticles exhibited high cell uptake andNotch1gene knockdown efficiency in SKOV3 cells at an nitrogen-to-phosphate ratio of 100 and an siRNA concentration of 50 nM. They also inhibited the growth and promoted the apoptosis of SKOV3 cells. These results may provide the potential for using cationic cholesterol derivatives as efficient nonviral siRNA carriers for the suppression of Notch1 activation in ovarian cancer cells.
authors: Pharmacy Department, Women's Hospital.
authors: Yun-Chun
authors: YC
authors: Zhao
authors: Pharmacy Department, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors: Li
authors: L
authors: Zhang
authors: Department of Pharmaceutic Preparation, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou.
authors: Shi-Sen
authors: SS
authors: Feng
authors: Department of Pharmaceutic Preparation, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou.
authors: Lu
authors: L
authors: Hong
authors: Department of Pharmaceutic Preparation, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou.
authors: Hai-Li
authors: HL
authors: Zheng
authors: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors: Li-Li
authors: LL
authors: Chen
authors: Pharmacy Department, Women's Hospital.
authors: Xiao-Ling
authors: XL
authors: Zheng
authors: Pharmacy Department, Women's Hospital.
authors: Yi-Qing
authors: YQ
authors: Ye
authors: Pharmacy Department, Women's Hospital.
authors: Meng-Dan
authors: MD
authors: Zhao
authors: Department of Pharmaceutic Preparation, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou.
authors: Wen-Xi
authors: WX
authors: Wang
authors: Pharmacy Department, Women's Hospital.
authors: Cai-Hong
authors: CH
authors: Zheng
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001152:Arsenicals / Q000737:chemistry; D002412:Cations; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation; D002784:Cholesterol / Q000031:analogs & derivatives*; D005260:Female; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D053758:Nanoparticles; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D010316:Particle Size; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism; D044967:Serum / Q000737:chemistry; D014162:Transfection
chemical_list: D001152:Arsenicals; D002412:Cations; D008081:Liposomes; C497761:NOTCH1 protein, human; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; C044974:dimethylarsinopenicillamine; D002784:Cholesterol
keywords: Notch1; cationic cholesterol derivative; ovarian cancer cells; siRNA