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Issue 13, 2011
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Preparation and biological evaluation of self-assembled cubic phases for the polyvalent inhibition of cholera toxin

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Abstract

The inverse cubic phase derived from the self-assembly of surfactants in water offers a unique three-dimensional platform for protein binding. Colloidally stable, sub-micron dispersions of the inverse bicontinuous cubic phase (cubosomes) impart an unusually large interfacial area for presentation of small molecules to selectively bind proteins of interest. Cubosomes of the phytantriol/water system were prepared and the receptor for cholera toxin (CT), monosialoganglioside GM1 (GM1), was integrated within the cubic phase. Our results show that GM1-functionalised cubosomes display a strong inhibitory response against CT with a high specificity for the toxin. Surface plasmon resonance (SPR) studies demonstrate that CT and cholera toxin B subunit (CTB) both specifically bind and form a very stable complex with GM1phytantriol cubosomes, demonstrated by an absence of binding to control proteins (mouse IgG, lysozyme and ricin). The inhibitory activity of the GM1–phytantriol cubosomes against CT was evaluated by a modified enzyme linked immunosorbent assay (ELISA). Using this method we have determined a nanomolar inhibitory activity (e.g., IC50 = 2.31 nM against 10 ng ml−1 CT) for these particles and a dissociation constant of the GM1–CT complex (KD) of 1.75 nM, highlighting the remarkable inhibitory activity of the self-assembled cubic phase systems.

Graphical abstract: Preparation and biological evaluation of self-assembled cubic phases for the polyvalent inhibition of cholera toxin

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Publication details

The article was received on 11 Mar 2011, accepted on 15 Apr 2011 and first published on 26 May 2011


Article type: Paper
DOI: 10.1039/C1SM05428G
Citation: Soft Matter, 2011,7, 6125-6134
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    Preparation and biological evaluation of self-assembled cubic phases for the polyvalent inhibition of cholera toxin

    S. J. Fraser, R. Rose, M. K. Hattarki, P. G. Hartley, O. Dolezal, R. M. Dawson, F. Separovic and A. Polyzos, Soft Matter, 2011, 7, 6125
    DOI: 10.1039/C1SM05428G

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