siRNA delivery into tumor cells by cationic cholesterol derivative-based nanoparticles and liposomes.
Previously, we reported that cationic nanoparticles (NP) composed of diamine-type cholesteryl-3-carboxamide (OH-Chol, N-(2-(2-hydroxyethylamino)ethyl)cholesteryl-3-carboxamide) and Tween 80 could deliver small interfering RNA (siRNA) with high transfection efficiency into tumor cells. In this study, we synthesized new diamine-type cationic cholesteryl carbamate (OH-C-Chol, cholesteryl (2-((2-hydroxyethyl)amino)ethyl)carbamate) and triamine-type carbamate (OH-NC-Chol, cholesteryl (2-((2-((2-hydroxyethyl)amino)ethyl)amino)ethyl)carbamate), and prepared cationic nanoparticles composed of OH-C-Chol or OH-NC-Chol with Tween 80 (NP-C and NP-NC, respectively), as well as cationic liposomes composed of OH-C-Chol or OH-NC-Chol with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) (LP-C and LP-NC, respectively) for evaluation of their possible use as siRNA delivery vectors. LP-C and LP-NC/siRNA complexes (lipoplexes) exhibited larger gene silencing effects than NP-C and NP-NC/siRNA complexes (nanoplexes), respectively, in human breast tumor MCF-7 cells, although the NP-C nanoplex showed high association with the cells. In particular, LP-NC lipoplex could induce strong gene suppression, even at a concentration of 5 nM siRNA. From these results, cationic liposomes composed of OH-NC-Chol and DOPE may have potential as gene vectors for siRNA transfection to tumor cells.
Institute of Medicinal Chemistry, Hoshi University.
Yoshiyuki
Y
Hattori
Eriko
E
Hara
Yumiko
Y
Shingu
Daiki
D
Minamiguchi
Ayako
A
Nakamura
Shohei
S
Arai
Hiroaki
H
Ohno
Kumi
K
Kawano
Nobutaka
N
Fujii
Etsuo
E
Yonemochi
D000818:Animals; D002219:Carbamates / Q000737:chemistry; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry*; D005260:Female; D006801:Humans; D008081:Liposomes; D049409:Luciferases, Firefly / Q000235:genetics; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009369:Neoplasms / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry*
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D002219:Carbamates; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011136:Polysorbates; D034741:RNA, Small Interfering; D002784:Cholesterol; D049409:Luciferases, Firefly