siRNA delivery into tumor cells by lipid- based nanoparticles composed of hydroxyethylated cholesteryl triamine

作者：Hattori Yoshiyuki^*; Nakamura Tsukasa; Ohno Hiroaki; Fujii Nobutaka; Maitani Yoshie

来源：International Journal of Pharmaceutics, 2013, 443(1-2): 221-229.

DOI：10.1016/j.ijpharm.2012.12.017

• Cationic nanoparticles
• siRNA delivery
• Transfection
• Cholesteryl diamine
• Cholesteryl triamine

Previously, we reported that cationic nanoparticles (NP) composed of cholesteryl diamine (OH-Chol, (3S)-N-(2-(2-hydroxyethylamino)ethyl)cholesteryl-3-carboxamide) and Tween 80 could deliver plasmid DNA (pDNA) and small interfering RNA (siRNA) with high transfection efficiency into various tumor cells. In this study, to facilitate the endosomal escape of siRNA transfected by lipid-based nanoparticles, we synthesized new cationic cholesteryl triamine (OH-N-Chol, (3S)-N-(2-(2( 2-hydroxyethylamino)ethylamino)ethyl)cholesteryl-3-carboxamide) with an ethylenimine extension and prepared cationic nanoparticles (NP-N) composed of cholesteryl triamine and Tween 80. Although NP-N/siRNA complex (NP-N nanoplex) after mixing NP-N with siRNA was > 350 nm in size, the vortex-mixing during the nanoplex formation decreased it to about 200 nm, which was an injectable size. NP-N nanoplex was mainly internalized by macropinocytosis-mediated endocytosis, as was NP nanoplex, and showed higher gene knockdown efficiency than NP nanoplex in human cervical carcinoma SiHa cells. From these results, cationic nanoparticles composed of OH-N-Chol and Tween 80 may have potential as a gene vector for siRNA transfection to tumor cells.

• 出版日期2013-2-25
• 单位河北医科大学