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Novel cationic cardiolipin analogue-based liposome for efficient DNA and small interfering RNA delivery in vitro and in vivo

Cancer Gene Therapy volume 12, pages 321–328 (2005)Cite this article

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.

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Abbreviations

CCLA:

cationic cardiolipin analogue

siRNA:

small interfering RNA

DOTAP:

1,2,-dioleoyl-3-trimethylammoniumpropane

DOTMA:

1,2-dioleyloxypropyl-3-trimethylammonium chloride

DOSPA:

2,3-dioleoyloxy-N-[2- (spermine-carboxamido)ethyl]-N,N-dimethyl-1-propanaminium

DOPE:

dioleoylphosphatidylethanolamine

DOPC:

dioleoylphosphatidylcholine

HI-FBS:

heat-inactivated fetal bovine serum

SRB:

sulforhodamine B

β-gal:

β-galactosidase

iv:

intravenous

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Authors and Affiliations

  1. Research and Development, NeoPharm Inc., Waukegan, Illinois, USA

    Pei-Yu Chien, Jinkang Wang, Danielle Carbonaro, Sabrina Lei, Bruce Miller, Saifuddin Sheikh, Shoukath M Ali, Moghis U Ahmad & Imran Ahmad

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  1. Pei-Yu Chien
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  2. Jinkang Wang
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Correspondence to Imran Ahmad.

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Chien, PY., Wang, J., Carbonaro, D. et al. Novel cationic cardiolipin analogue-based liposome for efficient DNA and small interfering RNA delivery in vitro and in vivo. Cancer Gene Ther 12, 321–328 (2005). https://doi.org/10.1038/sj.cgt.7700793

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