Preparation and biological evaluation of self-assembled cubic phases for the polyvalent inhibition of cholera toxin
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...
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Veröffentlicht in: | Soft matter 2011-01, Vol.7 (13), p.6125-6134 |
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Hauptverfasser: | , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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 GM1-phytantriol 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. |
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ISSN: | 1744-683X 1744-6848 |
DOI: | 10.1039/c1sm05428g |