Issue 13, 2011

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

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

Article information

Article type
Paper
Submitted
11 Mar 2011
Accepted
15 Apr 2011
First published
26 May 2011

Soft Matter, 2011,7, 6125-6134

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

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements