Targeting G Protein‐Coupled Receptors with Magnetic Carbon Nanotubes: The Case of the A3 Adenosine Receptor

F. Pineux, S. Federico, K. N. Klotz, S. Kachler, C. Michiels, M. Sturlese, M. Prato, G. Spalluto, S. Moro, D. Bonifazi.

ChemMedChem, 2020, 15, 1909 –1920.

DOI: 10.1002/cmdc.202000466


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.

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