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 and Notch1 gene 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.

Keywords:

• siRNA
• cationic cholesterol derivative
• Notch1
• ovarian cancer cells

Acknowledgments

This work was financially supported by National Natural Science Foundation of China, General Program (nos 81173000, 81102396, 81201606, and 81200428) and Natural Science Foundation of Zhejiang Province, People’s Republic of China (nos LY14H300005 and LY16H160025).

Disclosure

The authors report no conflicts of interest in this work.