Functionalization of immunostimulating complexes (ISCOMs) with lipid vinyl sulfones and their application in immunological techniques and therapy

Abstract

Teresa Cruz-Bustos,1,* Gloria González-González,1,* Julia Morales-Sanfrutos,2 Alicia Megía-Fernández,2 Francisco Santoyo-González,2 Antonio Osuna1 1Molecular Biochemistry and Parasitology Research Group, Department of Parasitology, Institute of Biotechnology, Faculty of Sciences, University of Granada, Granada, Spain; 2Department of Organic Chemistry, Institute of Biotechnology, Faculty of Sciences, University of Granada, Granada, Spain *These authors contributed equally to this workBackground: Immunostimulating complexes (ISCOM)-type nanocapsules have been functionalized with lipid vinyl sulfones that anchor to them via the hydrophobic zone of their structure and can be charged with pharmacologically active molecules or macromolecules. These functionalized nanocapsules can incorporate protein A and bind to G immunoglobulins (IgGs) to make vehicles directed at the surface antigens of infectious agents, tumor cells, or receptor cells and deliver the encapsulated molecules in a highly specific way. They may be of particular use in pharmacological treatments with highly toxic molecules that should not be used in solution whenever it can be avoided. When bound to antibodies they can be used in biological processes that require the delivery or presentation of macromolecules to certain specific cells, in immunization processes for instance, or in diagnostic immunological techniques, as they are able to transport both the secondary antibodies and the reaction labels.Methods and results: We describe the preparation of ISCOMs, the binding to the ISCOMS of newly synthesized compounds composed of chain alkyl vinyl sulfone, and the subsequent binding of the vinyl-sulfone compounds to IgGs. Within this context, a compound deriving from cholesterol functionalized with vinyl sulfone and used together with cholesterol in varying proportions has been linked to the structure of the ISCOMs and bound to protein A–IgG. This functionalization in no way altered the form or structure of the ISCOMs and allowed the nanocapsules carrying the specific IgGs to bind to forms of Trypanosoma cruzi against which antibodies had been developed. The fact that functionalized ISCOMs containing antibodies could deliver actinomycin D directly to the parasite meant that the effective dose of the antibiotic could be reduced very significantly.Conclusion: We have developed ISCOM-type nanocapsules functionalized with lipid vinyl sulfone capable of anchoring to the surface of functional IgGs, which favors the recognition and transport of these nanocapsules precisely to certain kinds of cell.Keywords: nanoparticle, protein A, actinomycin D, IgG, Trypanosoma cruzi, vinyl sulfone