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Issue 4, 2019
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Peptide-grafted dextran vectors for efficient and high-loading gene delivery

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Abstract

Among various polymeric gene delivery systems, peptide-based vectors demonstrate great potential owing to their unique structure and properties, including flexibility; however, there is insufficient molecular understanding of the role and properties of amino acids as building blocks in gene delivery. In this work, we constructed a series of histidine (H)-containing peptide-grafted dextran (D-RxHy) vectors via a simple two-step reaction of dextran with five RxHyC peptides: R7H3C, R5H3C, R5H5C, R3H5C, and R3H7C. The gel electrophoresis study unveiled the DNA-binding ability of H residues. While all D-RxHy vectors possess similarly low cytotoxicity, D-R3H7 exhibited the highest gene transfection efficiency. Interestingly, at the low nitrogen to phosphate (N/P) ratio of 2, D-R3H7 displayed a 6–8-fold higher luciferase expression compared to the gold standard branched PEI (25k). D-R3H7 and D-R5H5 demonstrated favorable cell uptake rates. A chloroquine-treated transfection assay confirmed the key effect of the high buffering capacity of H-rich D-R3H7 on its high gene transfection efficiency, especially at low N/P ratios. The present work unveiled that histidine is critical for both DNA condensation and the accurate control of endosomal escape. The tunable D-RxHy platform not only demonstrates promising potential for therapeutic purposes but can also be used as a tool to elucidate the molecular mechanism of polymer-based transfection.

Graphical abstract: Peptide-grafted dextran vectors for efficient and high-loading gene delivery

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Publication details

The article was received on 23 Oct 2018, accepted on 10 Jan 2019 and first published on 25 Jan 2019


Article type: Paper
DOI: 10.1039/C8BM01341A
Citation: Biomater. Sci., 2019,7, 1543-1553

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    Peptide-grafted dextran vectors for efficient and high-loading gene delivery

    Y. Hu, H. Wang, H. Song, M. Young, Y. Fan, F. Xu, X. Qu, X. Lei, Y. Liu and G. Cheng, Biomater. Sci., 2019, 7, 1543
    DOI: 10.1039/C8BM01341A

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