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Antiangiogenic gene therapy with systemically administered sFlt-1 plasmid DNA in engineered gelatin-based nanovectors

Cancer Gene Therapy volume 14, pages 488–498 (2007)Cite this article

Abstract

This study examined the potential of engineered gelatin-based nanoparticulate vectors for systemic delivery of therapeutic genes to human solid tumor xenografts in vivo. Plasmid DNA encoding for the soluble form of the extracellular domain of vascular endothelial growth factor receptor-1 (VEGF-R1 or sFlt-1) was encapsulated in the control and poly(ethylene glycol) (PEG)-modified gelatin-based nanoparticles. When the plasmid DNA was delivered in PEG-modified thiolated gelatin nanoparticles, highest levels of sFlt-1 expression was observed in vitro in MDA-MB-435 human breast adenocarcinoma cell line. In addition, upon intravenous administration in female Nu/Nu mice bearing orthotopic MDA-MB-435 breast adenocarcinoma xenografts, efficient in vivo expression of sFlt-1 plasmid DNA was confirmed quantitatively by enzyme-linked immunosorbent assay and qualitatively by Western blot analysis. The expressed sFlt-1 was therapeutically active as shown by suppression of tumor growth and microvessel density measurements. The results of this study show that PEG-modified gelatin-based nanovectors can serve as a safe and effective systemically administered gene delivery vehicle for solid tumor.

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Acknowledgements

This study was supported by a grant R01-CA095522 from the National Cancer Institute of the National Institutes of Health (NIH). We thank Professor Kensuke Egashira of Kyushu University (Fukuoka, Japan) for providing us with the sample of human sFlt-1 expressing plasmid. Additionally, Dr Lara Gamble's help with the ESCA investigations at the NESAC/BIO (Seattle, WA) is gratefully acknowledged. NESAC/BIO is supported by the National Institutes of Health grant EB-002027.

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  1. Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA, USA

    S Kommareddy & M Amiji

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  1. S Kommareddy
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Correspondence to M Amiji.

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Kommareddy, S., Amiji, M. Antiangiogenic gene therapy with systemically administered sFlt-1 plasmid DNA in engineered gelatin-based nanovectors. Cancer Gene Ther 14, 488–498 (2007). https://doi.org/10.1038/sj.cgt.7701041

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