Original Article

Cancer Gene Therapy (2008) 15, 496–507; doi:10.1038/cgt.2008.26; published online 16 May 2008

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

R A Abela1, J Qian1, L Xu1, T S Lawrence1 and M Zhang1

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

Correspondence: Dr M Zhang, Department of Radiation Oncology, University of Michigan, 1331 E Ann Street, Room 3030, Ann Arbor, MI 48109-0582, USA. E-mail: mingz@med.umich.edu

Received 11 October 2007; Revised 17 January 2008; Accepted 21 February 2008; Published online 16 May 2008.

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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 (10–20Gy) 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.

Keywords:

ionizing radiation, cationic liposome, nanoparticles, transferring receptor, lung cancer