Radiation improves gene delivery by a novel transferrin-lipoplex nanoparticle selectively in cancer cells
Radiation improves gene delivery by a novel transferrin-lipoplex nanoparticle selectively in cancer cells
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DOI：
10.1038/cgt.2008.26
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发表时间：
2008-08-01
影响因子：
6.4
通讯作者：
Zhang, M.
中科院分区：
文献类型：
--
作者：
Abela, R. A.;Qian, J.;Zhang, M.
肿瘤的选择性基因转移是肿瘤基因治疗的关键。我们以前使用电离辐射来提高肝内肿瘤对腺病毒的摄取，但仍然发生了与病毒给药相关的肝细胞毒性。在这里，我们探索了一种模仿病毒的纳米粒子-转铁蛋白(Tf)-阳离子脂质体-DNA复合体(Tf-Lipoplex)-辐射改善基因传递的潜力。Tf-Lipoplex在不同的细胞系中的转导效率很高，并以剂量和时间依赖的方式被辐射进一步增加。这种辐射诱导与Tf-Lipoplex摄取增加(肝细胞WB和肺癌细胞LLC1的3-4倍)有关，但当使用Tf缺乏的复合体或用游离Tf取消时，这种辐射诱导是不存在的，这表明辐射诱导需要Tf受体(TfR)相互作用。辐射(10~20Gy)可显著诱导LLC1裸鼠移植瘤中转基因(LacZ)的表达(3.5~7.4倍)，并与照射后肿瘤中质粒含量和TfR表达的增加有关。此外，在肝脏或其他正常组织中未观察到Tf-Lipoplex介导的基因表达，无论放射治疗如何。我们得出结论，无论是在体外还是在体内，辐射都能选择性地促进TF-Lipoplex基因向肿瘤细胞的传递。我们的发现可能为开发分子靶向癌症基因治疗的配体特异性脂复合体提供洞察力。
Selective gene transfer to tumor is critical in cancer gene therapy. We previously used ionizing radiation to improve adenovirus uptake in intrahepatic tumors but liver cytotoxicity associated with the viral administration still occurred. Here, we explore the potential of radiation for improving gene delivery by a virus-mimicking nanoparticle, transferrin (Tf)-cationic liposome-DNA complex (Tf-lipoplex). Transduction by Tf-lipoplex was highly efficient in various cell lines and further increased by radiation in a dose- and time-dependent manner. This radiation induction, which was associated with an increase in Tf-lipoplex uptake (3- to 4-folds in hepatocytes WB and lung cancer cells, LLC1), was absent when a Tf-deficient complex was used or abolished by the presence of free Tf, suggesting that Tf receptor (TfR) interaction is required for radiation induction. Radiation (10-20 Gy) markedly induced transgene (LacZ) expression in LLC1 xenografts (3.5- to 7.4-folds), correlating with increased plasmid content and TfR expression in irradiated tumors. Moreover, Tf-lipoplex-mediated gene expression was not observed in the liver or other normal tissues regardless of radiation treatment. We conclude that radiation improves Tf-lipoplex gene delivery selectively to tumor cells both in vitro and in vivo. Our findings may provide insight in developing ligand-specific lipoplex for molecularly targeted cancer gene therapy.