Targeting G protein-coupled receptors with magnetic carbon nanotubes: The A3 adenosine receptor case

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. Fe-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 Fe-filled CNTs with the aim to target cells overexpressing A 3 ARs. In particular, two conjugates bearing PEG linkers of different length were designed. A docking analysis on the A 3 AR showed that both CNT and linker do not interfere with ligand binding to the receptor, that 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 where our compound resulted to not be selective for A 3 AR-cancer cells. Despite this, it is the first time that a GPCR ligand was anchored to a magnetic nanosystem, thus it opens the door to new applications for cancer treatment.