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Biodegradable Dextran Nanogels for RNA Interference: Focusing on Endosomal Escape and Intracellular siRNA Delivery

Koen Raemdonck UGent, Broes Naeye UGent, Kevin Buyens UGent, Roosmarijn Vandenbroucke UGent, A Hogset, Jo Demeester UGent and Stefaan De Smedt UGent (2009) Advanced Functional Materials. 19(9). p.1406-1415
abstract
The successful therapeutic application of small interfering RNA (siRNA) largely relies on the development of safe and effective delivery systems that are able to guide the siRNA therapeutics to the cytoplasm of the target cell. In this report, biodegradable cationic dextran nanogels are engineered by inverse emulsion photopolymerization and their potential as siRNA carriers is evaluated. The nanogels are able to entrap siRNA with a high loading capacity, based on electrostatic interaction. Confocal microscopy and flow cytometry analysis reveal that large amounts of siRNA-loaded nanogels can be internalized by HuH-7 human hepatoma cells without significant cytotoxicity. Following their cellular uptake, it is found that the nanogels are mainly trafficked towards the endolysosomes. The influence of two different strategies to enhance endosomal escape on the extent of gene silencing is investigated. It is found that both the application of photochemical internalization (PCI) and the use of an influenza-derived fusogenic peptide (diINF-7) can significantly improve the silencing efficiency of siRNA-loaded nanogels. Furthermore, it is shown that an efficient gene silencing requires the degradation of the nanogels. As the degradation kinetics of the nanogels can easily be tailored, these particles show potential for intracellular controlled release of short interfering RNA
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
COMPLEXES, INTEGRITY, PHOTOCHEMICAL INTERNALIZATION, FLUORESCENCE FLUCTUATION SPECTROSCOPY, THERAPEUTICS, DRUG-DELIVERY, PATHWAYS, RECEPTOR, STRATEGIES, OLIGONUCLEOTIDES
journal title
Advanced Functional Materials
Adv. Funct. Mater.
volume
19
issue
9
pages
1406 - 1415
publisher
Wiley
Web of Science type
Article
Web of Science id
000266285400010
JCR category
PHYSICS, APPLIED
JCR impact factor
6.99 (2009)
JCR rank
5/104 (2009)
JCR quartile
1 (2009)
ISSN
1616-301X
DOI
10.1002/adfm.200801795
language
English
UGent publication?
yes
classification
A1
copyright statement
I don't know the status of the copyright for this publication
id
688720
handle
http://hdl.handle.net/1854/LU-688720
date created
2009-06-10 15:24:25
date last changed
2009-06-17 14:41:56
@article{688720,
  abstract     = {The successful therapeutic application of small interfering RNA (siRNA) largely relies on the development of safe and effective delivery systems that are able to guide the siRNA therapeutics to the cytoplasm of the target cell. In this report, biodegradable cationic dextran nanogels are engineered by inverse emulsion photopolymerization and their potential as siRNA carriers is evaluated. The nanogels are able to entrap siRNA with a high loading capacity, based on electrostatic interaction. Confocal microscopy and flow cytometry analysis reveal that large amounts of siRNA-loaded nanogels can be internalized by HuH-7 human hepatoma cells without significant cytotoxicity. Following their cellular uptake, it is found that the nanogels are mainly trafficked towards the endolysosomes. The influence of two different strategies to enhance endosomal escape on the extent of gene silencing is investigated. It is found that both the application of photochemical internalization (PCI) and the use of an influenza-derived fusogenic peptide (diINF-7) can significantly improve the silencing efficiency of siRNA-loaded nanogels. Furthermore, it is shown that an efficient gene silencing requires the degradation of the nanogels. As the degradation kinetics of the nanogels can easily be tailored, these particles show potential for intracellular controlled release of short interfering RNA},
  author       = {Raemdonck, Koen and Naeye, Broes and Buyens, Kevin and Vandenbroucke, Roosmarijn and Hogset, A and Demeester, Jo and De Smedt, Stefaan},
  issn         = {1616-301X},
  journal      = {Advanced Functional Materials},
  keyword      = {COMPLEXES,INTEGRITY,PHOTOCHEMICAL INTERNALIZATION,FLUORESCENCE FLUCTUATION SPECTROSCOPY,THERAPEUTICS,DRUG-DELIVERY,PATHWAYS,RECEPTOR,STRATEGIES,OLIGONUCLEOTIDES},
  language     = {eng},
  number       = {9},
  pages        = {1406--1415},
  publisher    = {Wiley},
  title        = {Biodegradable Dextran Nanogels for RNA Interference: Focusing on Endosomal Escape and Intracellular siRNA Delivery},
  url          = {http://dx.doi.org/10.1002/adfm.200801795},
  volume       = {19},
  year         = {2009},
}

Chicago
Raemdonck, Koen, Broes Naeye, Kevin Buyens, Roosmarijn Vandenbroucke, A Hogset, Jo Demeester, and Stefaan De Smedt. 2009. “Biodegradable Dextran Nanogels for RNA Interference: Focusing on Endosomal Escape and Intracellular siRNA Delivery.” Advanced Functional Materials 19 (9): 1406–1415.
APA
Raemdonck, K., Naeye, B., Buyens, K., Vandenbroucke, R., Hogset, A., Demeester, J., & De Smedt, S. (2009). Biodegradable Dextran Nanogels for RNA Interference: Focusing on Endosomal Escape and Intracellular siRNA Delivery. Advanced Functional Materials, 19(9), 1406–1415.
Vancouver
1.
Raemdonck K, Naeye B, Buyens K, Vandenbroucke R, Hogset A, Demeester J, et al. Biodegradable Dextran Nanogels for RNA Interference: Focusing on Endosomal Escape and Intracellular siRNA Delivery. Advanced Functional Materials. Wiley; 2009;19(9):1406–15.
MLA
Raemdonck, Koen, Broes Naeye, Kevin Buyens, et al. “Biodegradable Dextran Nanogels for RNA Interference: Focusing on Endosomal Escape and Intracellular siRNA Delivery.” Advanced Functional Materials 19.9 (2009): 1406–1415. Print.