title: siRNA delivery into tumor cells by lipid-based nanoparticles composed of hydroxyethylated cholesteryl triamine.
abstract: 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.
authors.affiliation: Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan. yhattori@hoshi.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hattori
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Nakamura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohno
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani
mesh_terms: D002412:Cations; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004705:Endocytosis; D004983:Ethanolamines / Q000138:chemical synthesis / Q000737:chemistry*; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D006801:Humans; D049409:Luciferases, Firefly / Q000235:genetics; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D013499:Surface Properties; D014162:Transfection
chemical_list: D002412:Cations; D004337:Drug Carriers; D004983:Ethanolamines; C582849:N-(2-(2-(2-hydroxyethylamino)ethylamino)ethyl)cholesteryl-3-carboxamide; D034741:RNA, Small Interfering; D002784:Cholesterol; D049409:Luciferases, Firefly