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Issue 30, 2017
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Dextranated poly(urethane amine)s designed for systemic gene delivery in ovarian cancer therapy

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Abstract

Herein, comb-shaped polycations with neutral dextran as the main chain and folate-coupled bioreducible poly(urethane amine) (PUA) as the graft were designed and prepared as non-viral vectors for intravenous gene delivery targeting in tumor-bearing nude mice. Herein, primary amine-terminal PUAs with varied degrees of polymerization (DP) were prepared and then conjugated to dextrans with different molecular weights (5 kDa or 10 kDa), producing comb-shaped dextran-PUA polycations (denoted as Dex-PUA). The terminal group of the PUA graft could be further modified with folate, yielding folate-coupled Dex-PUA (denoted as Dex-PUA-FA). These comb-shaped polycations can condense genes into colloidal stable polyplexes under physiological conditions. However, these nano-polyplexes liberated genes in response to a reductive intracellular environment. In vitro transfection experiments showed that Dex10k-PUA40-FA, with 10 kDa dextran and a PUA oligomer with DP 40, induced the best transfection efficiency against SKOV-3 ovarian cancer cells in 10% serum. In vivo, the Dex10k-PUA40-FA polyplexes were applicable for intravenous gene delivery targeting SKOV-3 tumors in nude mice, affording a higher level of gene accumulation in the tumor as compared to Dex10k-PUA40 polyplexes lacking folate. Additionally, in vivo gene therapy showed that using a small hairpin RNA-silencing vascular endothelial growth factor, the Dex10k-PUA40-FA polyplexes exerted significant growth inhibition of SKOV-3 tumors with negligible systemic toxicity. The results of this study highlight dextranated PUA as a safe and robust gene vector for non-viral cancer gene therapy.

Graphical abstract: Dextranated poly(urethane amine)s designed for systemic gene delivery in ovarian cancer therapy

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Publication details

The article was received on 15 Jun 2017, accepted on 13 Jul 2017 and first published on 13 Jul 2017


Article type: Paper
DOI: 10.1039/C7TB01641G
Citation: J. Mater. Chem. B, 2017,5, 6119-6127
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    Dextranated poly(urethane amine)s designed for systemic gene delivery in ovarian cancer therapy

    J. Zhao, F. Han, P. Zhao, X. Wen and C. Lin, J. Mater. Chem. B, 2017, 5, 6119
    DOI: 10.1039/C7TB01641G

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