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Dextranated Poly(Urethane Amine)s Designed for Systemic Gene Delivery in Ovarian Cancer Therapy

Abstract

Comb-shaped polycations having neutral dextran as the main chain and folate-coupled bioreducible poly(urethane amine) (denoted as PUA) as the graft were designed and prepared as non-viral vectors for intravenous gene delivery targeting tumor bearing in nude mice. Herein, primary amine-terminal PUA at varied degree of polymerization (DP) were prepared and then conjugated to the dextran at different molecular weight (5kDa or 10kDa), producing comb-shaped dextran-PUA polycations (denoted as Dex-PUA). The terminal group of PUA graft could be further modified with folate, yielding folate-coupled Dex-PUA (denoted as Dex-PUA-FA). These comb-shaped polycations could condense genes into colloidal stable polyplexes under physiological conditions. However, these nano-polyplexes liberated genes in response to an intracellular reductive environment. In vitro transfection experiments showed that Dex10k-PUA40-FA having 10kDa dextran and PUA oligomer at DP 40 induced the best transfection efficiency against SKOV-3 ovarian cancer cells in 10% serum. In vivo, the polyplexes of Dex10k-PUA40-FA were applicable for intravenous gene delivery targeting SKOV-3 tumor bearing in a nude mouse, affording higher level of gene accumulation in the tumor as compared to those of Dex10k-PUA40 lacking the folate. Besides, in vivo gene therapy showed that, using small hairpin RNA silencing vascular endothelial growth factor, Dex10k-PUA40-FA polyplexes exerted significant growth inhibition of SKOV-3 tumor with negligible systemic toxicity. The results of this work highlight dextranated PUA as a safe and robust gene vector for non-viral cancer gene 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, Accepted Manuscript
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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, Accepted Manuscript , DOI: 10.1039/C7TB01641G

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