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Comparison of polymeric siRNA nanocarriers in a murine LPS-activated macrophage cell line: gene silencing, toxicity and off-target gene expression

Jensen, Linda B, Griger, Joscha, Naeye, Broes, Varkouhi, Amir K, Raemdonck, Koen UGent, Schiffelers, Raymond, Lammers, Twan, Storm, Gert, De Smedt, Stefaan UGent, Sproat, Brian S, et al. (2012) PHARMACEUTICAL RESEARCH. 29(3). p.669-682
abstract
Tumor necrosis factor alpha (TNF-alpha) plays a key role in the progression of rheumatoid arthritis and is an important target for anti-rheumatic therapies. TNF-alpha expression can be silenced with small interfering RNA (siRNA), but efficacy is dependent on efficient and safe siRNA delivery vehicles. We aimed to identify polymeric nanocarriers for anti-TNF-alpha siRNA with optimal efficacy and minimal off-target effects in vitro. TNF-alpha silencing with polymeric siRNA nanocarriers was compared in lipopolysaccharide-activated RAW 264.7 macrophages by real-time reverse transcription (RT)-PCR. Expression of non-target genes involved in inflammation, apoptosis, and cell cycle progression was determined by RT-PCR, toxicity evaluated by propidium iodide and annexin V staining. PAMAM dendrimers (G4 and G7) and dextran nanogels mediated remarkably high concentration-dependent gene silencing and low toxicity; dioleoyltrimethylammoniumpropane-modified poly(DL-lactide-co-glycolide acid) nanoparticles, thiolated, trimethylated chitosan and poly[(2-hydroxypropyl)methacrylamide 1-methyl-2-piperidine methanol] polyplexes were less efficient transfectants. There were minor changes in the regulation of off-target genes, mainly dependent on nanocarrier and siRNA concentration. Dextran nanogels and PAMAM dendrimers mediated high gene silencing with minor toxicity and off-target transcriptional changes and are therefore expected to be suitable siRNA delivery systems in vivo.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
NECROSIS-FACTOR-ALPHA, RHEUMATOID-ARTHRITIS, EPITHELIAL A549 CELLS, DRUG-DELIVERY SYSTEMS, COLLAGEN-INDUCED ARTHRITIS, BIODEGRADABLE DEXTRAN NANOGELS, SMALL INTERFERING RNA, TNF-alpha, siRNA, polymer, delivery, macrophages, IN-VIVO, DNA COMPLEXES, CANCER-CELLS
journal title
PHARMACEUTICAL RESEARCH
Pharm. Res.
volume
29
issue
3
pages
669 - 682
Web of Science type
Article
Web of Science id
000300457500005
JCR category
PHARMACOLOGY & PHARMACY
JCR impact factor
4.742 (2012)
JCR rank
25/259 (2012)
JCR quartile
1 (2012)
ISSN
0724-8741
DOI
10.1007/s11095-011-0589-0
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2137021
handle
http://hdl.handle.net/1854/LU-2137021
date created
2012-06-08 11:21:47
date last changed
2016-12-19 15:39:04
@article{2137021,
  abstract     = {Tumor necrosis factor alpha (TNF-alpha) plays a key role in the progression of rheumatoid arthritis and is an important target for anti-rheumatic therapies. TNF-alpha expression can be silenced with small interfering RNA (siRNA), but efficacy is dependent on efficient and safe siRNA delivery vehicles. We aimed to identify polymeric nanocarriers for anti-TNF-alpha siRNA with optimal efficacy and minimal off-target effects in vitro. 
TNF-alpha silencing with polymeric siRNA nanocarriers was compared in lipopolysaccharide-activated RAW 264.7 macrophages by real-time reverse transcription (RT)-PCR. Expression of non-target genes involved in inflammation, apoptosis, and cell cycle progression was determined by RT-PCR, toxicity evaluated by propidium iodide and annexin V staining. 
PAMAM dendrimers (G4 and G7) and dextran nanogels mediated remarkably high concentration-dependent gene silencing and low toxicity; dioleoyltrimethylammoniumpropane-modified poly(DL-lactide-co-glycolide acid) nanoparticles, thiolated, trimethylated chitosan and poly[(2-hydroxypropyl)methacrylamide 1-methyl-2-piperidine methanol] polyplexes were less efficient transfectants. There were minor changes in the regulation of off-target genes, mainly dependent on nanocarrier and siRNA concentration. 
Dextran nanogels and PAMAM dendrimers mediated high gene silencing with minor toxicity and off-target transcriptional changes and are therefore expected to be suitable siRNA delivery systems in vivo.},
  author       = {Jensen, Linda B and Griger, Joscha and Naeye, Broes and Varkouhi, Amir K and Raemdonck, Koen and Schiffelers, Raymond and Lammers, Twan and Storm, Gert and De Smedt, Stefaan and Sproat, Brian S and Nielsen, Hanne M and Foged, Camilla},
  issn         = {0724-8741},
  journal      = {PHARMACEUTICAL RESEARCH},
  keyword      = {NECROSIS-FACTOR-ALPHA,RHEUMATOID-ARTHRITIS,EPITHELIAL A549 CELLS,DRUG-DELIVERY SYSTEMS,COLLAGEN-INDUCED ARTHRITIS,BIODEGRADABLE DEXTRAN NANOGELS,SMALL INTERFERING RNA,TNF-alpha,siRNA,polymer,delivery,macrophages,IN-VIVO,DNA COMPLEXES,CANCER-CELLS},
  language     = {eng},
  number       = {3},
  pages        = {669--682},
  title        = {Comparison of polymeric siRNA nanocarriers in a murine LPS-activated macrophage cell line: gene silencing, toxicity and off-target gene expression},
  url          = {http://dx.doi.org/10.1007/s11095-011-0589-0},
  volume       = {29},
  year         = {2012},
}

Chicago
Jensen, Linda B, Joscha Griger, Broes Naeye, Amir K Varkouhi, Koen Raemdonck, Raymond Schiffelers, Twan Lammers, et al. 2012. “Comparison of Polymeric siRNA Nanocarriers in a Murine LPS-activated Macrophage Cell Line: Gene Silencing, Toxicity and Off-target Gene Expression.” Pharmaceutical Research 29 (3): 669–682.
APA
Jensen, L. B., Griger, J., Naeye, B., Varkouhi, A. K., Raemdonck, K., Schiffelers, R., Lammers, T., et al. (2012). Comparison of polymeric siRNA nanocarriers in a murine LPS-activated macrophage cell line: gene silencing, toxicity and off-target gene expression. PHARMACEUTICAL RESEARCH, 29(3), 669–682.
Vancouver
1.
Jensen LB, Griger J, Naeye B, Varkouhi AK, Raemdonck K, Schiffelers R, et al. Comparison of polymeric siRNA nanocarriers in a murine LPS-activated macrophage cell line: gene silencing, toxicity and off-target gene expression. PHARMACEUTICAL RESEARCH. 2012;29(3):669–82.
MLA
Jensen, Linda B, Joscha Griger, Broes Naeye, et al. “Comparison of Polymeric siRNA Nanocarriers in a Murine LPS-activated Macrophage Cell Line: Gene Silencing, Toxicity and Off-target Gene Expression.” PHARMACEUTICAL RESEARCH 29.3 (2012): 669–682. Print.