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Radiation improves gene delivery by a novel transferrin-lipoplex nanoparticle selectively in cancer cells

Cancer Gene Therapy volume 15, pages 496–507 (2008)Cite this article

Abstract

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.

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Acknowledgements

We thank Mary Davis (Radiation Oncology, University of Michigan) for her review of the paper. This work was supported partly by NIH grants CA80145, CA121830, CA128220, and CA84117, and the Cancer Center Core Grant CA46592 from the University of Michigan.

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  1. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA

    R A Abela, J Qian, L Xu, T S Lawrence & M Zhang

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  1. R A Abela
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  2. J Qian
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  3. L Xu
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  4. T S Lawrence
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  5. M Zhang
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Correspondence to M Zhang.

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Abela, R., Qian, J., Xu, L. et al. Radiation improves gene delivery by a novel transferrin-lipoplex nanoparticle selectively in cancer cells. Cancer Gene Ther 15, 496–507 (2008). https://doi.org/10.1038/cgt.2008.26

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