TY - JOUR
T1 - Targeting G protein-coupled receptors with magnetic carbon nanotubes
T2 - The Case of the A
3 Adenosine Receptor
AU - Pineux, Florent
AU - Federico, Stephanie
AU - Klotz, Karl-Norbert
AU - Kachler, Sonja
AU - Michiels, Carine
AU - Sturlese, Mattia
AU - Prato, Maurizio
AU - Spalluto, Giampiero
AU - Moro, Stefano
AU - Bonifazi, Davide
N1 - Funding Information:
The MMS lab is very grateful to Chemical Computing Group, OpenEye, and Acellera for scientific and technical partnership. They also gratefully acknowledges the support of the NVIDIA Corporation through the donation of the Titan V GPU used for this research. The authors thank the Morph-Im UNamur technological platform. M.P. is the AXA Chair for Carbon Bionanotechnology (2016-2023). This work was supported by the University of Trieste, INSTM. Part of this work was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency grant no. MDM-2017-0720.
Funding Information:
The MMS lab is very grateful to Chemical Computing Group, OpenEye, and Acellera for scientific and technical partnership. They also gratefully acknowledges the support of the NVIDIA Corporation through the donation of the Titan V GPU used for this research. The authors thank the Morph‐Im UNamur technological platform. M.P. is the AXA Chair for Carbon Bionanotechnology (2016‐2023). This work was supported by the University of Trieste, INSTM. Part of this work was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency grant no. MDM‐2017‐0720.
Publisher Copyright:
© 2020 Wiley-VCH GmbH
PY - 2020/10/19
Y1 - 2020/10/19
N2 - 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.
AB - 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.
KW - A adenosine receptors
KW - G protein-coupled receptors
KW - carbon nanotubes
KW - docking
KW - magnetic cell sorting
KW - theranostics
UR - http://www.scopus.com/inward/record.url?scp=85090443351&partnerID=8YFLogxK
U2 - 10.1002/cmdc.202000466
DO - 10.1002/cmdc.202000466
M3 - Article
C2 - 32706529
SN - 1860-7179
VL - 15
SP - 1909
EP - 1920
JO - ChemMedChem
JF - ChemMedChem
IS - 20
ER -
