Abstract
In the field of molecular imaging, selectivity for target cells is a key determinant of the degree of imaging contrast. Previously, we developed a pre-targeted method by which target cells could be selectively imaged using a labeled N-glycan that was ligated in situ with an integrin-targeted cyclic RGD peptide on the cell surface. Here we demonstrate the power of our method in discriminating various cancerous and non-cancerous cells that cannot be distinguished using conventional RGD ligands. Using four cyclic RGDyK peptides with various linker lengths with five N-glycans, we identify optimal combinations to discriminate six types of αvβ3 integrin–expressing cells on 96-well plates. The optimal combinations of RGD and N-glycan ligands for the target cells are fingerprinted on the plates, and then used to selectively image tumors in xenografted mouse models. Using this method, various N-glycan molecules, even those with millimolar affinities for their cognate lectins, could be used for selective cancer cell differentiation.
Highlights
In the field of molecular imaging, selectivity for target cells is a key determinant of the degree of imaging contrast
This glycan has only weak affinity for PECAM, which is selectively expressed on HUVECs; weak binding to the pretargeted HUVECs selectively anchored the fluorescence to the cell through the strain-promoted azide-alkyne cycloaddition (SPAAC) reaction, which was facilitated by the proximal effects between the two surface receptors
The azide function was introduced onto the cyclic RGDyK peptide ligands (Fig. 2, 1a–d) through various lengths of polyethylene glycol (PEG) linkers, i.e., PEG3, PEG5, PEG7, or PEG9, in order to investigate the distance dependence of the click reaction, which dictated the spatial arrangement between the ligand/receptor complexes that was tolerated in the context of the labeling reaction
Summary
In the field of molecular imaging, selectivity for target cells is a key determinant of the degree of imaging contrast. HUVECs (human umbilical vein endothelial cells) from cancerous HeLa cells (human cervical cancer cells), both of which express common receptors such as αvβ[3] integrins, by combining an RGD peptide with a glycan in a pre-targeted manner (Fig. 1c)[8].
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