PH-sensitive toxins: interactions with membrane bilayers and application to drug delivery

pH-sensitive toxins are secreted by bacteria and reach the cytosol of eukaryotic target cells by complex mechanisms involving receptor binding, membrane interaction and translocation across a cell lipid membrane. Membrane interaction and ability to reach the cytoplasm have been used respectively to present proteins at the cell surface and to transport foreign peptides or DNA into the cytoplasm. The first approach is used in anticancer vaccination and the second in inducing a major histocompatibility (MHC) class I presentation of exogenous peptides or proteins. A brief overview of the use of toxins themselves for targeting cancer cells is also presented. Altogether, the data suggest that pH sensitive toxins have a huge potential for surface presentation or cytosol transport of biomacromolecules and that many ways could still be explored to develop new strategies in vaccination or therapeutic methods. (C) 2004 Elsevier B.V. All rights reserved.