Abstract
This investigation aims to determine experimentally whether or not ultrasound (US) irradiation is effective in enhancing the in vivo gene expression of NK4 plasmid DNA and suppressing tumor growth. NK4, composed of the NH2-terminal hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF), acts as an HGF-antagonist and angiogenesis inhibitor. Dextran was cationized by introducing spermine to the hydroxyl groups to allow for polyionic complexation with NK4 plasmid DNA. The cationized dextran was additionally modified with poly(ethylene glycol) (PEG) molecules giving PEG engrafted cationized dextran. Significant suppression of tumor growth was observed when PEG engrafted cationized dextran–NK4 plasmid DNA complexes were intravenously injected into mice carrying a subcutaneous Lewis lung carcinoma tumor mass with subsequent US irradiation when compared with the cationized dextran–NK4 plasmid DNA complex and naked NK4 plasmid DNA with or without US irradiation. We conclude that complexation with PEG-engrafted cationized dextran in combination with US irradiation is a promising way to target the NK4 plasmid DNA to the tumor for gene expression.
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Acknowledgements
The Japan Society for the Promotion of Science (JSPS) is greatly acknowledged for the support of this work.
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The authors have retracted this article because Figs. 4, 6 and 7 contain duplicated and modified figures from prior publications which have now been retracted.
All authors agree to this retraction.
An erratum to this article can be found online at http://dx.doi.org/10.1038/s41417-019-0148-0.
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Hosseinkhani, H., Kushibiki, T., Matsumoto, K. et al. RETRACTED ARTICLE: Enhanced suppression of tumor growth using a combination of NK4 plasmid DNA-PEG engrafted cationized dextran complex and ultrasound irradiation. Cancer Gene Ther 13, 479–489 (2006). https://doi.org/10.1038/sj.cgt.7700918
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DOI: https://doi.org/10.1038/sj.cgt.7700918
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