Novel cationic cardiolipin analogue-based liposome for efficient DNA and small interfering RNA delivery in vitro and in vivo
Novel cationic cardiolipin analogue-based liposome for efficient DNA and small interfering RNA delivery in vitro and in vivo
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DOI：
10.1038/sj.cgt.7700793
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发表时间：
2005-03-01
影响因子：
6.4
通讯作者：
Ahmad, I
中科院分区：
文献类型：
--
作者：
Chien, PY;Wang, JK;Ahmad, I
阳离子脂质体已被成功地用作病毒系统输送核酸的替代方法。然而，目前可用的脂质体存在着高毒性和不稳定的转染率。因此，基于合成的阳离子心磷脂类似物(CCLA)，开发了一种新型阳离子脂质体来检测DNA的转染率。以CCLA为基础的脂质体也被用来检测c-raf小干扰RNA(SiRNA)在小鼠体内的治疗效果。在这篇报道中，我们证明了以CCLA为基础的脂质体在体外和体内都是毒性较小的，并且有效地转染了报告基因。在小鼠体内的转染率是商业上可获得的DOTAP脂质体的7倍。此外，在以CCLA为基础的脂质体存在的情况下，c-raf siRNA在癌细胞中诱导了高达62%的生长抑制。与游离c-raf siRNA组相比，c-raf siRNA/CCLA复合体对荷人乳腺移植瘤的SCID小鼠的肿瘤生长抑制率为73%。综上所述，基于CCLA的新型脂质体在体内外均表现出较低的毒性和广泛的应用前景。
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.