Structural characterization of a new lipid/DNA complex showing a selective transfection efficiency in ovarian cancer cells

Caracciolo, Giulio; Pozzi, Daniela; Caminiti, Ruggero; Castellano, A. Congiu

doi:10.1140/epje/i2002-10117-x

Cited by 43 publications

(38 citation statements)

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“…Cationic lipids and cationic polymers have been extensively studied for gene transfer experiments, during the last two decades [4][5][6][7][8][9] . In spite of a few limitations, such as a relatively low transfection rate and some intrinsic cell toxicity, these cationic agents are considered as a valid alternative to viral vectors [10][11][12]. Indeed, cationic polymers and liposomes are generally non-immunogenic, easy to produce, and non-oncogenic.…”

Section: Introductionmentioning

confidence: 99%

DOTAP/DOPE and DC-Chol/DOPE lipoplexes for gene delivery studied by circular dichroism and other biophysical techniques

Ciani

Casini

Gabbiani

et al. 2007

Biophysical Chemistry

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Cationic liposomes give rise to stable complexes with DNA molecules ( lipoplexes) that are of great interest for gene delivery applications. In particular, liposomes made up by a cationic lipid (DOTAP or DC-Chol) and a zwitterionic lipid (DOPE), produce stable adducts with single and double -stranded DNA oligonucleotides. Formation of these lipople xes has been further addressed here by circular dichroism spectroscopy (CD) and by other independent biophysical methods. Titration of DNA oligonucleotides with cationic liposomes resulted into significant modifications of their circular dichroic bands. Such spectral modifications were ascribed to progressive DNA condensation and loss of native conformation, as a consequence of the electrostatic interactions taking place between the phosphate groups of DNA and the positively charged head groups of cationic lipids. In all cases, the loss of the CD features characteristic of the native DNA conformation closely matched the inflection point of zeta potential profiles. The resulting adducts showed peculiar and non-canonical CD spectra, while exhibiting appreciable stability at physiological pH.

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Section: Introductionmentioning

confidence: 99%

DOTAP/DOPE and DC-Chol/DOPE lipoplexes for gene delivery studied by circular dichroism and other biophysical techniques

Ciani

Casini

Gabbiani

et al. 2007

Biophysical Chemistry

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“…[1][2][3][4] In acute dermal and epidermal wounds, liposomal gene transfer of genes coding for growth factors was shown effective in improving dermal and epidermal regeneration. 1,[5][6][7] Therefore, we used the physiologic cascade of wound healing as a model to investigate the effect of non-viral liposomal gene transfer.…”

Section: Introductionmentioning

confidence: 99%

The combination of IGF-I and KGF cDNA improves dermal and epidermal regeneration by increased VEGF expression and neovascularization

Jeschke

Herndon

2007

Gene Ther

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“…Some earlier studies suggested that the inverted hexagonal phase leads to more efficient transfection efficiency than does the lamellar phase (13,14). Recent experiments dispute this suggestion, however, and there is considerable evidence against a direct general correlation between lipoplex structure and transfection efficiency (15)(16)(17)(18)(19)(20)(21). Furthermore, a viewpoint now emerging is that the critical factor in lipid-mediated transfection is the structural evolution of lipoplexes upon interacting and mixing with cellular lipids (7)(8)(9).…”

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confidence: 99%

An intracellular lamellar–nonlamellar phase transition rationalizes the superior performance of some cationic lipid transfection agents

Koynova

Wang

MacDonald

2006

Proc. Natl. Acad. Sci. U.S.A.

149

163

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Two cationic phospholipid derivatives with asymmetric hydrocarbon chains were synthesized: ethyl esters of oleoyldecanoylethylphosphatidylcholine (C18:1͞C10-EPC) and stearoyldecanoylethylphosphatidylcholine (C18:0͞C10-EPC). The former was 50 times more effective as a DNA transfection agent (human umbilical artery endothelial cells) than the latter, despite their similar chemical structure and virtually identical lipoplex organization. A likely reason for the superior effectiveness of C18:1͞C10-EPC relative to C18:0͞C10-EPC (and to many other cationic lipoids) was suggested by the phases that evolved when these lipoids were mixed with negatively charged membrane lipid formulations. The saturated C18:0͞C10-EPC remained lamellar in mixtures with biomembranemimicking lipid formulations [e.g., dioleoyl-phosphatidylcholine͞ dioleoyl-phosphatidylethanolamine͞dioleoyl-phosphatidylserine͞ cholesterol at 45:20:20:15 (wt͞wt)]; in contrast, the unsaturated C18:1͞C10-EPC exhibited a lamellar-nonlamellar phase transition in such mixtures, which took place at physiological temperatures, Ϸ37°C. As is well known, lipid vehicles exhibit maximum leakiness and contents release in the vicinity of phase transitions, especially those involving nonlamellar phase formation. Moreover, nonlamellar phase-forming compositions are frequently highly fusogenic. Indeed, FRET experiments showed that C18:1͞C10-EPC exhibits lipid mixing with negatively charged membranes that is several times more extensive than that of C18:0͞C10-EPC. Thus, C18:1͞C10-EPC lipoplexes are likely to easily fuse with membranes, and, as a result of lipid mixing, the resultant aggregates should exhibit extensive phase coexistence and heterogeneity, thereby facilitating DNA release and leading to superior transfection efficiency. These results highlight the phase properties of the carrier lipid͞cellular lipid mixtures as a decisive factor for transfection success and suggest a strategy for the rational design of superior cationic lipid carriers.lipofection ͉ lipoplex ͉ mesophase I mportant therapeutic procedures, such as gene transfection and gene silencing, require efficient delivery of genetic material to cells. Synthetic cationic lipoids, which form complexes (lipoplexes) with polyanionic DNA, are promising gene carriers (1). Understanding the mechanism of lipid-mediated DNA delivery (lipofection) is essential for the successful application and rational design and synthesis of novel cationic lipoid compounds for enhanced gene delivery. Although considerable improvement in the transfection properties of cationic lipoids has come from the synthesis of new kinds of cationic amphiphiles or from the inclusion of noncationic helper lipids, an effective alternative strategy was recently described: The combination of two cationic lipid derivatives having the same headgroup but different hydrocarbon chains can synergistically enhance transfection (2). For example, the optimal combination of the long chain͞medium chain lipoids, dioleoyl-and dilauroyl-ethylphosphatidylcholines, de...

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Structural characterization of a new lipid/DNA complex showing a selective transfection efficiency in ovarian cancer cells

Cited by 43 publications

References 0 publications

DOTAP/DOPE and DC-Chol/DOPE lipoplexes for gene delivery studied by circular dichroism and other biophysical techniques

DOTAP/DOPE and DC-Chol/DOPE lipoplexes for gene delivery studied by circular dichroism and other biophysical techniques

The combination of IGF-I and KGF cDNA improves dermal and epidermal regeneration by increased VEGF expression and neovascularization

An intracellular lamellar–nonlamellar phase transition rationalizes the superior performance of some cationic lipid transfection agents

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