Issue 9, 2012

Engineered polyethylenimine/graphene oxide nanocomposite for nuclear localized gene delivery

Abstract

Nuclear localized signals (NLS) capable of recognition by nuclear transport proteins can aid the nuclear translocation of the payloads. In this report, NLS peptide PKKKRKV (PV7, one of the primary NLS peptides) was introduced into GO-PEI (10 kDa)/DNA binary complexes to engineer a nuclei localized gene delivery system, based on electrostatic and hydrogen-bonded interactions. To assess the functional mechanism of NLS peptides in the GO-PEI system, the PV7 was introduced via three different routes, including post-addition after the formation of a GO-PEI/DNA binary, simultaneous addition with GO-PEI, pDNA, and prior-addition into the cell culture before treatment with GO-PEI/DNA complexes. In vitro transfection investigations revealed that the ternary composites engineered by the simultaneous route (that is the second route referred to above) exhibit a higher transfection efficiency in comparison with GO-PEI 10 kDa or PEI 10 kDa and are even comparable with PEI 25 kDa with optimized parameters. The study on the intracellular uptake of Cy3 labeled pDNA indicated that the addition of PV7 could effectively assist the GO-PEI to deliver plasmid DNA directly into the nucleus without obvious aggregations. With the improved capability of gene delivery, however, the cytotoxicity of GO-PEI was much lower than PEI 10 kDa and PEI 25 kDa against both HeLa cells and 293 T cells. Therefore, the PV7 conjugated GO-PEI system compromised the contradiction between the cytotoxicity and transfection efficiency, which could be an alternative strategy for a nuclear targeted gene delivery vehicle.

Graphical abstract: Engineered polyethylenimine/graphene oxide nanocomposite for nuclear localized gene delivery

Article information

Article type
Paper
Submitted
15 May 2012
Accepted
04 Jun 2012
First published
13 Jun 2012

Polym. Chem., 2012,3, 2561-2569

Engineered polyethylenimine/graphene oxide nanocomposite for nuclear localized gene delivery

T. Ren, L. Li, X. Cai, H. Dong, S. Liu and Y. Li, Polym. Chem., 2012, 3, 2561 DOI: 10.1039/C2PY20343J

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