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Nanomaterials functionalized with glucose have shown a great potential in cancer diagnosis and treatment. We have recently demonstrated that gold nanoparticles (GNP), functionalized with glucose, can be used for specific and sensitive tumor detection when combined with computed tomography (CT) - GNP functionalized with glucose in the second carbon position were used as a metabolically targeted contrast agents, and were able to discriminate between cancer and inflammation, which is a superior ability when comparing the FDG-PET which is not tumor specific. Here we aim to understand the uptake mechanisms of the glucose functionalized GNP using a comprehensive in vitro study in several cell types with different metabolic features, and examining the glucose transporter-1 (GLUT1) involvement in the uptake process. We found that the glucose functionalized GNP are not toxic to the cells in the tested concentrations and we demonstrate that the cellular uptake of GNP, when functionalized with glucose in the second carbon position, strongly depends on GLUT1 expression in the cells, which triggers clathrin-mediated endocytosis of the nanoparticles. This study can promote control and development of glucose-functionalized nanoparticles for many biological applications.
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