Cancer discrimination by on-cell N-glycan ligation.
Shogo NomuraYasuko EgawaSayaka UranoTsuyoshi TaharaYasuyoshi WatanabeKatsunori TanakaPublished in: Communications chemistry (2020)
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 α v β 3 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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- cell surface
- endoplasmic reticulum stress
- cell death
- magnetic resonance imaging
- squamous cell carcinoma
- magnetic resonance
- computed tomography
- signaling pathway
- machine learning
- young adults
- cancer therapy
- pi k akt
- cell therapy
- drug delivery
- heat stress
- positron emission tomography
- fluorescence imaging