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Targeting G Protein-Coupled Receptors with Magnetic Carbon Nanotubes: The Case of the A3 Adenosine Receptor |
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| Authors: | Dr Florent Pineux Dr Stephanie Federico Prof Karl-Norbert Klotz Sonja Kachler Dr Carine Michiels Dr Mattia Sturlese Prof Maurizio Prato Prof Giampiero Spalluto Prof Stefano Moro Davide Bonifazi |
| Affiliation: | 1. Department of Chemistry and Namur Research College (NARC), University of Namur, Rue de Bruxelles 61, 5000 Namur, Belgium;2. Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Trieste, Via L.Giorgeri 1, 34127 Trieste, Italy;3. Institut für Pharmakologie und Toxikologie, Universität Würzburg, Versbacher Straße 9, 97078 Würzburg, Germany;4. Namur Research Institute for Life Science (NARILIS), Unité de Recherche en Biologie Cellulaire (URBC), University of Namur, 5000 Namur, Belgium;5. Dipartimento di Scienze del Farmaco Molecular Modeling Section (MMS), Università degli Studi di Padova, Via F. Marzolo 5, 35131 Padova, Italy;6. Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Trieste, Via L.Giorgeri 1, 34127 Trieste, Italy
Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramón 182, 20014 Donostia-San Sebastián, Spain Basque Foundation for Science, Ikerbasque, 48013 Bilbao, Spain;7. Institut für Organische Chemie, Universität Wien, Währinger Str. 38, 1090 Wien, Austria |
| Abstract: | The A3 adenosine receptor (AR) is a G protein-coupled receptor (GPCR) overexpressed in the membrane of specific cancer cells. Thus, the development of nanosystems targeting this receptor could be a strategy to both treat and diagnose cancer. Iron-filled carbon nanotubes (CNTs) are an optimal platform for theranostic purposes, and the use of a magnetic field can be exploited for cancer magnetic cell sorting and thermal therapy. In this work, we have conjugated an A3AR ligand on the surface of iron-filled CNTs with the aim of targeting cells overexpressing A3ARs. In particular, two conjugates bearing PEG linkers of different length were designed. A docking analysis of A3AR showed that neither CNT nor linker interferes with ligand binding to the receptor; this was confirmed by in vitro preliminary radioligand competition assays on A3AR. Encouraged by this result, magnetic cell sorting was applied to a mixture of cells overexpressing or not the A3AR in which our compound displayed indiscriminate binding to all cells. Despite this, it is the first time that a GPCR ligand has been anchored to a magnetic nanosystem, thus it opens the door to new applications for cancer treatment. |
| Keywords: | A3 adenosine receptors carbon nanotubes docking G protein-coupled receptors magnetic cell sorting theranostics |