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Cellular gene delivery via poly(hexamethylene biguanide)/pDNA self-assembled nanoparticles

Chivu, A; Chindera, K; Mendes, G; An, A; Davidson, B; Good, L; Song, W; (2020) Cellular gene delivery via poly(hexamethylene biguanide)/pDNA self-assembled nanoparticles. European Journal of Pharmaceutics and Biopharmaceutics 10.1016/j.ejpb.2020.11.001. Green open access

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Abstract

Cellular gene delivery via polycations has wide implications for the potential of gene therapy, but it has remained a challenge due to the plethora of pre- and post-uptake barriers that must be overcome to reach desired efficiency. Herein we report poly(hexamethylene biguanide) (PHMB) as a nano-vector for intracellular delivery of plasmid DNA (pDNA) and oligodeoxynucleotides (ODNs). PHMB and pDNA or ODNs self-assembled into complex nanoparticles at different pH values (7.4 and 12). Their size, charge, cellular uptake, and gene-expression efficiency are assessed and compared to PEI analogues. The systematic results show that the nanoparticles are effective in delivering plasmid DNA and ODNs to model cell lines in culture (HepG2, HEK293T, HeLa), with measurable changes in gene expression levels, comparable to and, in some conditions, even higher than PEI. The well-accepted safety profile of PHMB makes it a valuable candidate for consideration as an effective intracellular DNA vector for further study and potential clinical translation.

Type: Article
Title: Cellular gene delivery via poly(hexamethylene biguanide)/pDNA self-assembled nanoparticles
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ejpb.2020.11.001
Publisher version: https://doi.org/10.1016/j.ejpb.2020.11.001
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Gene delivery, poly(hexamethylene biguanide) (PHMB), nanoparticles, self-assembly
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/10114631
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