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

Teresa Cruz-Bustos1 Molecular Biochemistry and Parasitology Research Group, Department of Parasitology, Institute of Biotechnology, Faculty of Sciences, University of Granada, Granada, Spain

Gloria González-González1 Molecular Biochemistry and Parasitology Research Group, Department of Parasitology, Institute of Biotechnology, Faculty of Sciences, University of Granada, Granada, Spain

Julia Morales-Sanfrutos2 Department of Organic Chemistry, Institute of Biotechnology, Faculty of Sciences, University of Granada, Granada, Spain

Alicia Megía-Fernández2 Department of Organic Chemistry, Institute of Biotechnology, Faculty of Sciences, University of Granada, Granada, Spain

Francisco Santoyo-González2 Department of Organic Chemistry, Institute of Biotechnology, Faculty of Sciences, University of Granada, Granada, Spain

Antonio Osuna1 Molecular Biochemistry and Parasitology Research Group, Department of Parasitology, Institute of Biotechnology, Faculty of Sciences, University of Granada, Granada, SpainCorrespondence[email protected]

Abstract

Background

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:

Acknowledgments

This research was financed by Spanish Ministry of Science and Technology grants AGL2011-26098 and CTQ2011- 29299-CO2-01. The authors thank J Trout of the University of Granada Scientific Translation Service for the English translation of their text.

Disclosure

The authors report no conflicts of interest in this work.

Supplementary materials

The ¹H NMR and ¹³C NMR were analyzed in a 300 MHz Varian Inova Unity with a broadband (¹³C and ¹H) probe.

Figure S1 ¹H NMR spectra for compound 4.

Figure S1 1H NMR spectra for compound 4.

Figure S2 ¹³C and DEPT NMR spectra for compound 4.

Figure S2 13C and DEPT NMR spectra for compound 4.

Figure S3 ¹H NMR spectra for compound 7.

Figure S3 1H NMR spectra for compound 7.

Figure S4 ¹³C and DEPT NMR spectra for compound 7.

Figure S4 13C and DEPT NMR spectra for compound 7.

Figure S5 ¹H NMR spectra for compound 9.

Figure S5 1H NMR spectra for compound 9.

Figure S6 ¹³C and DEPT NMR spectra for compound 9.