Chivu, A;
Chindera, K;
Mendes, G;
An, A;
Davidson, B;
Good, L;
Song, W;
(2021)
Cellular gene delivery via poly(hexamethylene biguanide)/pDNA self-assembled nanoparticles.
European Journal of Pharmaceutics and Biopharmaceutics
, 158
pp. 62-71.
10.1016/j.ejpb.2020.11.001.
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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.
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