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The effect of a nuclear localization sequence on transfection efficacy of genes delivered by cobalt(II)–polybenzimidazole complexes

Paper ID Volume ID Publish Year Pages File Format Full-Text
6506 492 2012 11 PDF Available
Title
The effect of a nuclear localization sequence on transfection efficacy of genes delivered by cobalt(II)–polybenzimidazole complexes
Abstract

We have demonstrated that the metal complexes of polybenzimidazoles are emerging likely as a new type of gene-delivery systems based on their strong DNA-condensing ability. However, the in vitro transfection efficacy of the DNA condensates formed with the metal complexes was relatively low. The positively charged peptides, such as cell-penetrating peptides and nuclear localization sequences (NLSs), have been reported to be capable of enhancing expression of the transgenes, likely as they promote entrance of their electrostatic complexes with DNA into the nuclear through nuclear pores. Here, we explored expression of the genes transferred by a series of Co(II) complexes in the presence of NLS (PKKKRKV) in normal and cancer cell lines. The results showed that the Co(II) complexes lead to the more pronounced DNA condensation in the presence of NLS than that in the absence of NLS. The binding of NLS prior to addition of the Co complexes can significantly reduce both the size and the population of the condensates at the given Co complexes/DNA ratios, compared with the NLS-free condensates. Meanwhile, the binding of NLS can considerably increase surface positive charges on the DNA nanoparticles. The suitable sizes and high surface positive charges facilitate the entrance of the nanoparticles into cells. Luciferase activity assay indicated that the transfection efficacy of the NLS-bound condensates was five-fold of that of the NLS-free ones in different cell lines, and comparable to that of the condensate formed with the commercially available carrier PEI. Moreover, cell viability assay of the NLS-bound condensates showed lower cytotoxicity than the NLS-free ones. Thus, the combination of NLS and cationic metal complexes might offer a new type of ternary delivery systems.

Keywords
Co(II)–polybenzimidazole complex; Nonviral gene carrier; NLS; Transfection
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The effect of a nuclear localization sequence on transfection efficacy of genes delivered by cobalt(II)–polybenzimidazole complexes
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 31, November 2012, Pages 7884–7894
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us