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Effective antitumor gene therapy delivered by polyethylenimine-conjugated stearic acid-g-chitosan oligosaccharide micelles

Gene Therapy volume 20, pages 597–606 (2013)Cite this article

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Abstract

Non-viral vesicle composing of low-molecular weight polyethylenimine-conjugated stearic acid-g-chitosan oligosaccharide (CSOSA-g-PEI) was synthesized for gene delivery and therapy. The synthesized CSOSA-g-PEI had good ion-buffer capabilities and DNA-binding capacity, which could form positively charged nano-sized particles (100–150 nm) with plasmid DNA; in vitro gene transfection tests demonstrated that CSOSA-g-PEI presented much lower cytotoxicity and corresponding transfection efficiency in comparison with Lipofectamine 2000 in both human cancer cells (Hela and MCF-7). The gene transfection of CSOSA-g-PEI/pDNA could be further enhanced in the presence of serum or by adding arginine during incubation of CSOSA-g-PEI micelles with plasmid DNA. The biodistribution experiments demonstrated CSOSA-g-PEI conjugate highly localized in the tumor tissue and indicated a persistently increased accumulation. In vivo antitumor activity results showed that CSOSA-g-PEI/plasmid pigment epithelium-derived factor formulation could effectively suppress the tumor growth (above 60% tumor inhibition) without systematic toxicity against animal body after intravenous injection.

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Acknowledgements

This work is supported by the National Nature Science Foundation of China under Contract 30873174 and 81072583, and the Nature Science Foundation of Zhejiang province under Contract z207489 and Y2090336, and Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents.

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  1. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PRC

    F-Q Hu, W-W Chen, M-D Zhao, H Yuan & Y-Z Du

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Correspondence to Y-Z Du.

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Hu, FQ., Chen, WW., Zhao, MD. et al. Effective antitumor gene therapy delivered by polyethylenimine-conjugated stearic acid-g-chitosan oligosaccharide micelles. Gene Ther 20, 597–606 (2013). https://doi.org/10.1038/gt.2012.72

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