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Title: Structural and transfection properties of amine-substituted gemini surfactant-based nanoparticles

Abstract

Increases in DNA transfection efficiencies for non-viral vectors can be achieved through rational design of novel cationic building blocks. Based on previous results examining DNA condensation by polyamines, novel gemini surfactants have been designed that incorporate aza or imino substituents within the spacer group in order to increase interactions with DNA and potentially improve their DNA transfection ability. Transfection efficiencies and cell toxicity of gemini nanoparticles constructed from plasmid DNA, gemini surfactant, and a neutral lipid were measured in COS7 cells using a luciferase assay. Structural properties of nanoparticles were examined by using circular dichroism, particle size, zeta potential, and small-angle X-ray scattering (SAXS) measurements. The incorporation of aza and imino substituents within the spacer group was observed to enhance the transfection ability of gemini surfactants. Incorporation of an imino group in the structure of the 1,9-bis(dodecyl)-1,1,9,9-tetramethyl-5-imino-1,9-nonanediammonium dibromide surfactant (12-7NH-12) resulted in a statistically significant (p < 0.01) 9-fold increase in transfection compared to an unsubstituted gemini surfactant and a 3-fold increase compared to the corresponding aza-substituted compound. A pH-dependent transition in size and zeta potential was observed to occur at pH 5.5 for complexes formed from the 12-7NH-12 compound. SAXS results show weakly ordered structures and the presence ofmore » multiple phases. The incorporation of a pH-active imino group within the spacer of the gemini surfactant results in a significant increase in transfection efficiency that can be related to both pH-induced changes in nanoparticle structure and the formation of multiple phases that more readily allow for membrane fusion that may facilitate DNA release.« less

Authors:
; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
929921
Report Number(s):
BNL-80512-2008-JA
TRN: US200822%%1094
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Gene Medicine; Journal Volume: 9; Journal Issue: 8
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; COMPLEXES; DICHROISM; DNA; EFFICIENCY; INTERACTIONS; LIPIDS; LUCIFERASE; MEMBRANES; PARTICLE SIZE; PLASMIDS; ELECTRIC POTENTIAL; ELECTRODYNAMICS; SCATTERING; SURFACTANTS; TOXICITY; VECTORS; X-RAY DIFFRACTION; national synchrotron light source

Citation Formats

Wettig,S., Badea, I., Donkuru, M., Verrall, R., and Foldvari, M.. Structural and transfection properties of amine-substituted gemini surfactant-based nanoparticles. United States: N. p., 2007. Web. doi:10.1002/jgm.1060.
Wettig,S., Badea, I., Donkuru, M., Verrall, R., & Foldvari, M.. Structural and transfection properties of amine-substituted gemini surfactant-based nanoparticles. United States. doi:10.1002/jgm.1060.
Wettig,S., Badea, I., Donkuru, M., Verrall, R., and Foldvari, M.. Mon . "Structural and transfection properties of amine-substituted gemini surfactant-based nanoparticles". United States. doi:10.1002/jgm.1060.
@article{osti_929921,
title = {Structural and transfection properties of amine-substituted gemini surfactant-based nanoparticles},
author = {Wettig,S. and Badea, I. and Donkuru, M. and Verrall, R. and Foldvari, M.},
abstractNote = {Increases in DNA transfection efficiencies for non-viral vectors can be achieved through rational design of novel cationic building blocks. Based on previous results examining DNA condensation by polyamines, novel gemini surfactants have been designed that incorporate aza or imino substituents within the spacer group in order to increase interactions with DNA and potentially improve their DNA transfection ability. Transfection efficiencies and cell toxicity of gemini nanoparticles constructed from plasmid DNA, gemini surfactant, and a neutral lipid were measured in COS7 cells using a luciferase assay. Structural properties of nanoparticles were examined by using circular dichroism, particle size, zeta potential, and small-angle X-ray scattering (SAXS) measurements. The incorporation of aza and imino substituents within the spacer group was observed to enhance the transfection ability of gemini surfactants. Incorporation of an imino group in the structure of the 1,9-bis(dodecyl)-1,1,9,9-tetramethyl-5-imino-1,9-nonanediammonium dibromide surfactant (12-7NH-12) resulted in a statistically significant (p < 0.01) 9-fold increase in transfection compared to an unsubstituted gemini surfactant and a 3-fold increase compared to the corresponding aza-substituted compound. A pH-dependent transition in size and zeta potential was observed to occur at pH 5.5 for complexes formed from the 12-7NH-12 compound. SAXS results show weakly ordered structures and the presence of multiple phases. The incorporation of a pH-active imino group within the spacer of the gemini surfactant results in a significant increase in transfection efficiency that can be related to both pH-induced changes in nanoparticle structure and the formation of multiple phases that more readily allow for membrane fusion that may facilitate DNA release.},
doi = {10.1002/jgm.1060},
journal = {Journal of Gene Medicine},
number = 8,
volume = 9,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}