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Unraveling the effects of siRNA carrier systems on cell physiology: a multiparametric approach demonstrated on dextran nanogels

Stefaan Soenen, Lynn De Backer, Bella Manshian, Shareen Doak, Koen Raemdonck UGent, Jo Demeester UGent, Kevin Braeckmans UGent and Stefaan De Smedt UGent (2014) NANOMEDICINE. 9(1). p.61-76
abstract
Aim: The extent of cell-nanoparticle interactions between a polycationic siRNA nanocarrier system (dextran nanogels) and cultured cells was analyzed. Materials & methods: A multiparametric methodology is introduced to examine the cytotoxic effects of a model siRNA carrier (dextran nanogels) on different cell types, including primary human cells. Using this methodology, the nontoxic concentration of nanogels could be defined and the mechanisms contributing to their toxic profile were unraveled. Results: Above the toxicity threshold, nanogels were found to induce oxidative stress and destabilize the plasma membrane. Furthermore, nanogel-induced cellular stress led to DNA damage, impeded cell functionality and intracellular signaling, resulting in unspecific regulation of gene expression. Conclusion: This methodology shows that current toxicity assays such as the 3-(4,5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide assay are not adequate to assess the full spectrum of cell-nanoparticle interactions and more in-depth studies are required.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
IN-VIVO, DELIVERY, TOXICITY, QUANTUM DOTS, GOLD NANOPARTICLES, INORGANIC NANOPARTICLES, toxicity mechanism, siRNA delivery carrier, nanotoxicity, oxidative stress, genotoxicity, nanogel, cell viability, NF-KAPPA-B, MECHANISMS, GENE-EXPRESSION, NANOTOXICITY
journal title
NANOMEDICINE
Nanomedicine
volume
9
issue
1
pages
61 - 76
Web of Science type
Article
Web of Science id
000328682500016
JCR category
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
JCR impact factor
5.413 (2014)
JCR rank
16/163 (2014)
JCR quartile
1 (2014)
ISSN
1743-5889
DOI
10.2217/nnm.12.208
project
Center for nano- and biophotonics (NB-Photonics)
language
English
UGent publication?
yes
classification
A1
additional info
the first two authors contributed equally to this work
copyright statement
I have transferred the copyright for this publication to the publisher
id
4253025
handle
http://hdl.handle.net/1854/LU-4253025
date created
2014-01-28 14:56:27
date last changed
2017-02-10 15:38:33
@article{4253025,
  abstract     = {Aim: The extent of cell-nanoparticle interactions between a polycationic siRNA nanocarrier system (dextran nanogels) and cultured cells was analyzed.
Materials \& methods: A multiparametric methodology is introduced to examine the cytotoxic effects of a model siRNA carrier (dextran nanogels) on different cell types, including primary human cells. Using this methodology, the nontoxic concentration of nanogels could be defined and the mechanisms contributing to their toxic profile were unraveled.
Results: Above the toxicity threshold, nanogels were found to induce oxidative stress and destabilize the plasma membrane. Furthermore, nanogel-induced cellular stress led to DNA damage, impeded cell functionality and intracellular signaling, resulting in unspecific regulation of gene expression.
Conclusion: This methodology shows that current toxicity assays such as the 3-(4,5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide assay are not adequate to assess the full spectrum of cell-nanoparticle interactions and more in-depth studies are required.},
  author       = {Soenen, Stefaan and De Backer, Lynn and Manshian, Bella and Doak, Shareen and Raemdonck, Koen and Demeester, Jo and Braeckmans, Kevin and De Smedt, Stefaan},
  issn         = {1743-5889},
  journal      = {NANOMEDICINE},
  keyword      = {IN-VIVO,DELIVERY,TOXICITY,QUANTUM DOTS,GOLD NANOPARTICLES,INORGANIC NANOPARTICLES,toxicity mechanism,siRNA delivery carrier,nanotoxicity,oxidative stress,genotoxicity,nanogel,cell viability,NF-KAPPA-B,MECHANISMS,GENE-EXPRESSION,NANOTOXICITY},
  language     = {eng},
  number       = {1},
  pages        = {61--76},
  title        = {Unraveling the effects of siRNA carrier systems on cell physiology: a multiparametric approach demonstrated on dextran nanogels},
  url          = {http://dx.doi.org/10.2217/nnm.12.208},
  volume       = {9},
  year         = {2014},
}

Chicago
Soenen, Stefaan, Lynn De Backer, Bella Manshian, Shareen Doak, Koen Raemdonck, Jo Demeester, Kevin Braeckmans, and Stefaan De Smedt. 2014. “Unraveling the Effects of siRNA Carrier Systems on Cell Physiology: a Multiparametric Approach Demonstrated on Dextran Nanogels.” Nanomedicine 9 (1): 61–76.
APA
Soenen, S., De Backer, L., Manshian, B., Doak, S., Raemdonck, K., Demeester, J., Braeckmans, K., et al. (2014). Unraveling the effects of siRNA carrier systems on cell physiology: a multiparametric approach demonstrated on dextran nanogels. NANOMEDICINE, 9(1), 61–76.
Vancouver
1.
Soenen S, De Backer L, Manshian B, Doak S, Raemdonck K, Demeester J, et al. Unraveling the effects of siRNA carrier systems on cell physiology: a multiparametric approach demonstrated on dextran nanogels. NANOMEDICINE. 2014;9(1):61–76.
MLA
Soenen, Stefaan, Lynn De Backer, Bella Manshian, et al. “Unraveling the Effects of siRNA Carrier Systems on Cell Physiology: a Multiparametric Approach Demonstrated on Dextran Nanogels.” NANOMEDICINE 9.1 (2014): 61–76. Print.