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-3-phosphoethanolamine (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.
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Authors | George R Dakwar, Kevin Braeckmans, Wim Ceelen, Stefaan C De Smedt, Katrien Remaut |
Journal | Drug delivery and translational research
(Drug Deliv Transl Res)
Vol. 7
Issue 2
Pg. 241-251
(04 2017)
ISSN: 2190-3948 [Electronic] United States |
PMID | 27631392
(Publication Type: Journal Article)
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Chemical References |
- Fatty Acids, Monounsaturated
- Liposomes
- Phosphatidylethanolamines
- Quaternary Ammonium Compounds
- RNA, Small Interfering
- polyethylene glycol-distearoylphosphatidylethanolamine
- Polyethylene Glycols
- 1,2-dielaidoylphosphatidylethanolamine
- Luciferases
- 1,2-dioleoyloxy-3-(trimethylammonium)propane
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Topics |
- Ascites
- Cell Line, Tumor
- Cell Survival
- Fatty Acids, Monounsaturated
(chemistry)
- Humans
- Liposomes
- Luciferases
(genetics)
- Phosphatidylethanolamines
(chemistry)
- Polyethylene Glycols
(chemistry)
- Quaternary Ammonium Compounds
(chemistry)
- RNA, Small Interfering
(administration & dosage, chemistry)
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