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Nanomedicine (Lond). 2015;10(18):2805-18. doi: 10.2217/nnm.15.105. Epub 2015 Jun 24.

Oxime ether lipids containing hydroxylated head groups are more superior siRNA delivery agents than their nonhydroxylated counterparts.

Author information

1
Gene Regulation & Chromosome Biology Lab, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA.
2
Department of Chemistry, University of Louisville, Louisville, KY 40292, USA.
3
Department of Chemistry, University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, NC 28223, USA.
4
Basic Research Lab, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA.
5
Basic Science Program, Leidos Biomedical Research, Inc., National Cancer Institute, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702-1201, USA.

Abstract

AIM:

To evaluate the structure-activity relationship of oxime ether lipids (OELs) containing modifications in the hydrophobic domains (chain length, degree of unsaturation) and hydrophilic head groups (polar domain hydroxyl groups) toward complex formation with siRNA molecules and siRNA delivery efficiency of resulting complexes to a human breast cancer cell line (MDA-MB-231).

MATERIALS & METHODS:

Ability of lipoplex formation between oxime ether lipids with nucleic acids were examined using biophysical techniques. The potential of OELs to deliver nucleic acids and silence green fluorescent protein (GFP) gene was analyzed using MDA-MB-231 and MDA-MB-231/GFP cells, respectively.

RESULTS & CONCLUSION:

Introduction of hydroxyl groups to the polar domain of the OELs and unsaturation into the hydrophobic domain favor higher transfection and gene silencing in a cell culture system.

KEYWORDS:

RNA interference; breast cancer cells; lipoplexes; nonsymmetric hydrophobic domain; oxime ether lipids; structure–activity relationship

PMID:
26107486
PMCID:
PMC4636123
DOI:
10.2217/nnm.15.105
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Financial & competing interests disclosure This research has been funded in whole or in part with Federal funds from the Frederick National Laboratory for Cancer Research, NIH, under contract HHSN261200800001E. This research was supported (in part) by the Intramural Research Program of NIH, Center for Cancer Research. RJ Knipp thanks the University of Louisville School of Interdisciplinary and Graduate Studies for fellowship support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

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