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Exploring the HYDRAtion method for loading siRNA on liposomes : the interplay between stability and biological activity in human undiluted ascites fluid

George Dakwar, Kevin Braeckmans UGent, Wim Ceelen UGent, Stefaan De Smedt UGent and Katrien Remaut UGent (2017) DRUG DELIVERY AND TRANSLATIONAL RESEARCH. 7(2). p.241-251
abstract
Delivery of small interfering RNA (siRNA) is recently gaining tremendous attention for the treatment of ovarian cancer. The present study investigated the potential of different liposomal formulations composed of (2,3-dioleoyloxy-propyl)trimethylammonium (DOTAP) and 1,2-dioleoyl-sn-glycero-3phosphoethanolamine (DOPE) encapsulating siRNA (hydration method) for their ability to knockdown luciferase (Luc) activity in human ovarian cancer SKOV-3 cells. Fluorescence single particle tracking (fSPT) and fluorescence correlation spectroscopy (FCS) in human-undiluted ascites fluid obtained from a peritoneal carcinomatosis patient revealed that cationic hydra-lipoplexes (HYDRA-LPXs) and HYDRA-LPXs decorated with stable DSPE-PEG (DSPE HYDRA-LPXs) showed high stability during at least 24 h. HYDRA-LPXs decorated with sheddable C8 and C16 PEG-Ceramides (Cer HYDRA-LPXs) resulted in rapid and premature release of siRNA already in the first hours. Despite their role in preventing aggregation in vivo, liposomes decorated with stable PEG residues resulted in a poor transfection compared to the ones decorated with sheddable PEG residues in reduced serum conditions. Yet, the transfection efficiency of both Cer HYDRA-LPXs significantly decreased following 1 h of incubation in ascites fluid due to a drastic drop in the cellular uptake, while DSPE HYDRA-LPXs are still taken up by cells, but too stable to induce efficient gene silencing.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
siRNA delivery, siRNA encapsulation, Peritoneal metastasis, Sheddable PEG, Ascites, PLASMID-LIPID PARTICLES, PEG IGM PRODUCTION, OVARIAN-CANCER, INTRACELLULAR TRAFFICKING, TRANSFECTION EFFICIENCY, INTRAPERITONEAL THERAPY, ENDOSOMAL ESCAPE, DELIVERY-SYSTEMS, CELLULAR UPTAKE, GENE DELIVERY
journal title
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
Drug Deliv. Transl. Res.
volume
7
issue
2
pages
241 - 251
Web of Science type
Article
Web of Science id
000397410400005
ISSN
2190-393X
2190-3948
DOI
10.1007/s13346-016-0329-4
project
Center for nano- and biophotonics (NB-Photonics)
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
8519490
handle
http://hdl.handle.net/1854/LU-8519490
date created
2017-05-04 08:09:37
date last changed
2017-06-12 14:06:00
@article{8519490,
  abstract     = {Delivery of small interfering RNA (siRNA) is recently gaining tremendous attention for the treatment of ovarian cancer. The present study investigated the potential of different liposomal formulations composed of (2,3-dioleoyloxy-propyl)trimethylammonium (DOTAP) and 1,2-dioleoyl-sn-glycero-3phosphoethanolamine (DOPE) encapsulating siRNA (hydration method) for their ability to knockdown luciferase (Luc) activity in human ovarian cancer SKOV-3 cells. Fluorescence single particle tracking (fSPT) and fluorescence correlation spectroscopy (FCS) in human-undiluted ascites fluid obtained from a peritoneal carcinomatosis patient revealed that cationic hydra-lipoplexes (HYDRA-LPXs) and HYDRA-LPXs decorated with stable DSPE-PEG (DSPE HYDRA-LPXs) showed high stability during at least 24 h. HYDRA-LPXs decorated with sheddable C8 and C16 PEG-Ceramides (Cer HYDRA-LPXs) resulted in rapid and premature release of siRNA already in the first hours. Despite their role in preventing aggregation in vivo, liposomes decorated with stable PEG residues resulted in a poor transfection compared to the ones decorated with sheddable PEG residues in reduced serum conditions. Yet, the transfection efficiency of both Cer HYDRA-LPXs significantly decreased following 1 h of incubation in ascites fluid due to a drastic drop in the cellular uptake, while DSPE HYDRA-LPXs are still taken up by cells, but too stable to induce efficient gene silencing.},
  author       = {Dakwar, George and Braeckmans, Kevin and Ceelen, Wim and De Smedt, Stefaan and Remaut, Katrien},
  issn         = {2190-393X},
  journal      = {DRUG DELIVERY AND TRANSLATIONAL RESEARCH},
  keyword      = {siRNA delivery,siRNA encapsulation,Peritoneal metastasis,Sheddable PEG,Ascites,PLASMID-LIPID PARTICLES,PEG IGM PRODUCTION,OVARIAN-CANCER,INTRACELLULAR TRAFFICKING,TRANSFECTION EFFICIENCY,INTRAPERITONEAL THERAPY,ENDOSOMAL ESCAPE,DELIVERY-SYSTEMS,CELLULAR UPTAKE,GENE DELIVERY},
  language     = {eng},
  number       = {2},
  pages        = {241--251},
  title        = {Exploring the HYDRAtion method for loading siRNA on liposomes : the interplay between stability and biological activity in human undiluted ascites fluid},
  url          = {http://dx.doi.org/10.1007/s13346-016-0329-4},
  volume       = {7},
  year         = {2017},
}

Chicago
Dakwar, George, Kevin Braeckmans, Wim Ceelen, Stefaan De Smedt, and Katrien Remaut. 2017. “Exploring the HYDRAtion Method for Loading siRNA on Liposomes : the Interplay Between Stability and Biological Activity in Human Undiluted Ascites Fluid.” Drug Delivery and Translational Research 7 (2): 241–251.
APA
Dakwar, G., Braeckmans, K., Ceelen, W., De Smedt, S., & Remaut, K. (2017). Exploring the HYDRAtion method for loading siRNA on liposomes : the interplay between stability and biological activity in human undiluted ascites fluid. DRUG DELIVERY AND TRANSLATIONAL RESEARCH, 7(2), 241–251.
Vancouver
1.
Dakwar G, Braeckmans K, Ceelen W, De Smedt S, Remaut K. Exploring the HYDRAtion method for loading siRNA on liposomes : the interplay between stability and biological activity in human undiluted ascites fluid. DRUG DELIVERY AND TRANSLATIONAL RESEARCH. 2017;7(2):241–51.
MLA
Dakwar, George, Kevin Braeckmans, Wim Ceelen, et al. “Exploring the HYDRAtion Method for Loading siRNA on Liposomes : the Interplay Between Stability and Biological Activity in Human Undiluted Ascites Fluid.” DRUG DELIVERY AND TRANSLATIONAL RESEARCH 7.2 (2017): 241–251. Print.