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Structural and transfection properties of amine‐substituted gemini surfactant‐based nanoparticles
Author(s) -
Wettig Shawn D.,
Badea Ildiko,
Donkuru McDonald,
Verrall Ronald E.,
Foldvari Marianna
Publication year - 2007
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1060
Subject(s) - transfection , zeta potential , circular dichroism , pulmonary surfactant , small angle x ray scattering , chemistry , cationic polymerization , amine gas treating , dna condensation , dna , nanoparticle , dynamic light scattering , nuclear chemistry , crystallography , organic chemistry , scattering , materials science , biochemistry , nanotechnology , physics , optics , gene
Background 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. Methods 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. Results 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. Conclusions 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. Copyright © 2007 John Wiley & Sons, Ltd.