Targeting G Protein-Coupled Receptors with Magnetic Carbon Nanotubes: The Case of the A 3 Adenosine Receptor.

The A ₃ 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 A ₃ AR ligand on the surface of iron-filled CNTs with the aim of targeting cells overexpressing A ₃ ARs. In particular, two conjugates bearing PEG linkers of different length were designed. A docking analysis of A ₃ AR showed that neither CNT nor linker interferes with ligand binding to the receptor; this was confirmed by in vitro preliminary radioligand competition assays on A ₃ AR. Encouraged by this result, magnetic cell sorting was applied to a mixture of cells overexpressing or not the A ₃ AR 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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