title: Novel cationic cardiolipin analogue-based liposome for efficient DNA and small interfering RNA delivery in vitro and in vivo.
abstract: Cationic liposomes have been successfully used as an alternative approach to viral systems to deliver nucleic acids. However, high toxicity and inconsistent transfection efficiency have been associated with the currently available liposomes. Therefore, a novel cationic liposome was developed based on a synthetic cationic cardiolipin analogue (CCLA) to test the DNA transfection efficiency. This CCLA-based liposome was also used to determine the therapeutic efficacy of c-raf small interfering RNA (siRNA) in mice. In this report, we showed that the CCLA-based liposome was less toxic and effectively transfected reporter genes in vitro and in vivo. The transfection efficiency in mice was seven-fold higher than the commercially available DOTAP-based liposome. In addition, c-raf siRNA in the presence of CCLA-based liposome induced up to 62% of growth inhibition in cancer cells. Treatment of c-raf siRNA/CCLA complex in SCID mice bearing human breast xenograft tumors resulted in 73% of tumor growth suppression as compared to free c-raf siRNA group. In conclusion, a novel CCLA-based liposome showed less toxicity and broad usage both in vitro and in vivo with DNA and siRNA.
authors.affiliation: Research and Development, NeoPharm Inc., Waukegan, Illinois 60085, USA.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Chien
authors.forename: Jinkang
authors.initials: J
authors.lastname: Wang
authors.forename: Danielle
authors.initials: D
authors.lastname: Carbonaro
authors.forename: Sabrina
authors.initials: S
authors.lastname: Lei
authors.forename: Bruce
authors.initials: B
authors.lastname: Miller
authors.forename: Saifuddin
authors.initials: S
authors.lastname: Sheikh
authors.forename: Shoukath M
authors.initials: SM
authors.lastname: Ali
authors.forename: Moghis U
authors.initials: MU
authors.lastname: Ahmad
authors.forename: Imran
authors.initials: I
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002308:Cardiolipins / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use* / Q000633:toxicity; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008081:Liposomes; D008156:Luciferases; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000633:toxicity; D012235:Rhodamines; D014162:Transfection / Q000379:methods*; D014183:Transplantation, Heterologous; D001616:beta-Galactosidase
chemical_list: D002308:Cardiolipins; D008081:Liposomes; D034741:RNA, Small Interfering; D012235:Rhodamines; C022027:lissamine rhodamine B; D004247:DNA; D008156:Luciferases; D019908:Proto-Oncogene Proteins c-raf; D001616:beta-Galactosidase