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

作者：Fraser Scott J; Rose Rachel; Hattarki Meghan K; Hartley Patrick G; Dolezal Olan; Dawson Raymond M; Separovic Frances; Polyzos Anastasios^*

来源：Soft Matter, 2011, 7(13): 6125-6134.

DOI：10.1039/c1sm05428g

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 G(M1) (G(M1)), was integrated within the cubic phase. Our results show that G(M1)-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 (CT(B)) both specifically bind and form a very stable complex with G(M1)-phytantriol cubosomes, demonstrated by an absence of binding to control proteins (mouse IgG, lysozyme and ricin). The inhibitory activity of the G(M1)-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., IC(50) = 2.31 nM against 10 ng ml(-1) CT) for these particles and a dissociation constant of the G(M1)-CT complex (K(D)) of 1.75 nM, highlighting the remarkable inhibitory activity of the self-assembled cubic phase systems.

• 出版日期2011
• 单位CSIRO