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Nuclear inclusion of nontargeted and chromatin-targeted polystyrene beads and plasmid DNA containing nanoparticles

Nathalie Symens UGent, Rudolf Walczak, Jo Demeester UGent, Iain Mattaj, Stefaan De Smedt UGent and Katrien Remaut UGent (2011) MOLECULAR PHARMACEUTICS. 8(5). p.1757-1766
abstract
The nuclear membrane is one of the major cellular barriers in the delivery of plasmid DNA (pDNA). Cell division has a positive influence on the expression efficiency since, at the end of mitosis, pDNA or pDNA containing complexes near the chromatin are probably included by a random process in the nuclei of the daughter cells. However, very little is known about the nuclear inclusion of nanoparticles during cell division. Using the Xenopus nuclear envelope reassembly (XNER) assay, we found that the nuclear enclosure of nanoparticles was dependent on size (with 100 and 200 nm particles being better included than the 500 nm ones) and charge (with positively charged particles being better included than negatively charged cr polyethyleneglycolated (PEGylated) ones) of the beads. Also, coupling chromatin-targeting peptides to the polystyrene beads or pDNA complexes improved their inclusion by 2- to 3-fold. Upon microinjection in living HeLa cells, however, nanoparticles were never observed in the nuclei of cells postdivision but accumulated in a specific perinuclear region, which was identified as the lysosomal compartment. This indicates that nanoparticles can end up in the lysosomes even when they were not delivered through endocytosis. To elucidate if the chromatin binding peptides also have potential in living cells, this additional barrier first has to be tackled, since it prevents free particles from being present near the chromatin at the moment of cell division.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
GOLD NANOPARTICLES, MITOTIC-ACTIVITY, AIRWAY EPITHELIAL-CELLS, MEDIATED GENE-TRANSFER, nuclear envelope reassembly, mitosis, nuclear exclusion, pDNA delivery, HeLa cells, Xenopus laevis, cell division, nuclear enclosure, IN-VITRO, EXPRESSION, CYCLE, TRANSFECTION, EFFICIENCY, CELLULAR UPTAKE
journal title
MOLECULAR PHARMACEUTICS
Mol. Pharm.
volume
8
issue
5
pages
1757 - 1766
Web of Science type
Article
Web of Science id
000295347500033
JCR category
PHARMACOLOGY & PHARMACY
JCR impact factor
4.782 (2011)
JCR rank
27/259 (2011)
JCR quartile
1 (2011)
ISSN
1543-8384
DOI
10.1021/mp200120v
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2134046
handle
http://hdl.handle.net/1854/LU-2134046
date created
2012-06-06 11:14:17
date last changed
2013-02-12 10:14:14
@article{2134046,
  abstract     = {The nuclear membrane is one of the major cellular barriers in the delivery of plasmid DNA (pDNA). Cell division has a positive influence on the expression efficiency since, at the end of mitosis, pDNA or pDNA containing complexes near the chromatin are probably included by a random process in the nuclei of the daughter cells. However, very little is known about the nuclear inclusion of nanoparticles during cell division. Using the Xenopus nuclear envelope reassembly (XNER) assay, we found that the nuclear enclosure of nanoparticles was dependent on size (with 100 and 200 nm particles being better included than the 500 nm ones) and charge (with positively charged particles being better included than negatively charged cr polyethyleneglycolated (PEGylated) ones) of the beads. Also, coupling chromatin-targeting peptides to the polystyrene beads or pDNA complexes improved their inclusion by 2- to 3-fold. Upon microinjection in living HeLa cells, however, nanoparticles were never observed in the nuclei of cells postdivision but accumulated in a specific perinuclear region, which was identified as the lysosomal compartment. This indicates that nanoparticles can end up in the lysosomes even when they were not delivered through endocytosis. To elucidate if the chromatin binding peptides also have potential in living cells, this additional barrier first has to be tackled, since it prevents free particles from being present near the chromatin at the moment of cell division.},
  author       = {Symens, Nathalie and Walczak, Rudolf and Demeester, Jo and Mattaj, Iain and De Smedt, Stefaan and Remaut, Katrien},
  issn         = {1543-8384},
  journal      = {MOLECULAR PHARMACEUTICS},
  keyword      = {GOLD NANOPARTICLES,MITOTIC-ACTIVITY,AIRWAY EPITHELIAL-CELLS,MEDIATED GENE-TRANSFER,nuclear envelope reassembly,mitosis,nuclear exclusion,pDNA delivery,HeLa cells,Xenopus laevis,cell division,nuclear enclosure,IN-VITRO,EXPRESSION,CYCLE,TRANSFECTION,EFFICIENCY,CELLULAR UPTAKE},
  language     = {eng},
  number       = {5},
  pages        = {1757--1766},
  title        = {Nuclear inclusion of nontargeted and chromatin-targeted polystyrene beads and plasmid DNA containing nanoparticles},
  url          = {http://dx.doi.org/10.1021/mp200120v},
  volume       = {8},
  year         = {2011},
}

Chicago
Symens, Nathalie, Rudolf Walczak, Jo Demeester, Iain Mattaj, Stefaan De Smedt, and Katrien Remaut. 2011. “Nuclear Inclusion of Nontargeted and Chromatin-targeted Polystyrene Beads and Plasmid DNA Containing Nanoparticles.” Molecular Pharmaceutics 8 (5): 1757–1766.
APA
Symens, N., Walczak, R., Demeester, J., Mattaj, I., De Smedt, S., & Remaut, K. (2011). Nuclear inclusion of nontargeted and chromatin-targeted polystyrene beads and plasmid DNA containing nanoparticles. MOLECULAR PHARMACEUTICS, 8(5), 1757–1766.
Vancouver
1.
Symens N, Walczak R, Demeester J, Mattaj I, De Smedt S, Remaut K. Nuclear inclusion of nontargeted and chromatin-targeted polystyrene beads and plasmid DNA containing nanoparticles. MOLECULAR PHARMACEUTICS. 2011;8(5):1757–66.
MLA
Symens, Nathalie, Rudolf Walczak, Jo Demeester, et al. “Nuclear Inclusion of Nontargeted and Chromatin-targeted Polystyrene Beads and Plasmid DNA Containing Nanoparticles.” MOLECULAR PHARMACEUTICS 8.5 (2011): 1757–1766. Print.