Transfection mediated by gemini surfactants: engineered escape from the endosomal compartment

Bell, Paul C., Bergsma, Mark, Dolbnya, Igor P., Bras, Wim, Stuart, Marc C. A., Rowan, Alan E., Feiters, Martinus C. and Engberts, Jan B. F. N. (2003) Transfection mediated by gemini surfactants: engineered escape from the endosomal compartment. Journal of the American Chemical Society, 125 6: 1551-1558. doi:10.1021/ja020707g

Author Bell, Paul C.
Bergsma, Mark
Dolbnya, Igor P.
Bras, Wim
Stuart, Marc C. A.
Rowan, Alan E.
Feiters, Martinus C.
Engberts, Jan B. F. N.
Title Transfection mediated by gemini surfactants: engineered escape from the endosomal compartment
Journal name Journal of the American Chemical Society   Check publisher's open access policy
ISSN 0002-7863
Publication date 2003-02-01
Year available 2003
Sub-type Article (original research)
DOI 10.1021/ja020707g
Open Access Status Not yet assessed
Volume 125
Issue 6
Start page 1551
End page 1558
Total pages 8
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Abstract The structure of the lipoplex formed from DNA and the sugar-based cationic gemini surfactant 1, which exhibits excellent transfection efficiency, has been investigated in the pH range 8.8-3.0 utilizing small-angle X-ray scattering (SAXS) and cryo-electron microscopy (cryo-TEM). Uniquely, three well-defined morphologies of the lipoplex were observed upon gradual acidification: a lamellar phase, a condensed lamellar phase, and an inverted hexagonal (HII) columnar phase. Using molecular modeling, we link the observed lipoplex morphologies and physical behavior to specific structural features in the individual surfactant, illuminating key factors in future surfactant design, viz., a spacer of six methylene groups, the presence of two nitrogens that can be protonated in the physiological pH range, two unsaturated alkyl tails, and hydrophilic sugar headgroups. Assuming that the mechanism of transfection by synthetic cationic surfactants involves endocytosis, we contend that the efficacy of gemini surfactant 1 as a gene delivery vehicle can be explained by the unprecedented observation of a pH-induced formation of the inverted hexagonal phase of the lipoplex in the endosomal pH range. This change in morphology leads to destabilization of the endosome through fusion of the lipoplex with the endosomal wall, resulting in release of DNA into the cytoplasm.
Keyword Chemistry, Multidisciplinary
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Australian Institute for Bioengineering and Nanotechnology Publications
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