Peptide-mediated cellular uptake of cryptophane

Cryptophane-A has generated considerable interest based on its high affinity for xenon and potential for creating biosensors for (129)Xe nuclear magnetic resonance (NMR) spectroscopy. Here, we report the cellular delivery of three peptide-functionalized cryptophane biosensors. Cryptophanes were delivered using two cationic cell penetrating peptides into several human cancer and normal cell lines. An RGD peptide targeting alpha(v)beta(3) integrin receptor was shown to increase specificity of cryptophane cell uptake. Labeling the peptides with Cy3 made it possible to monitor cellular delivery using confocal laser scanning microscopy. The peptido-cryptophanes were determined to be relatively nontoxic by MTT assay at the micromolar cryptophane concentrations that are required for (129)Xe NMR biosensing experiments.