Dendrimer display of tumor-homing peptides

In vivo selection of phage libraries that display random peptide sequences on their surface has yielded a number of peptides that specifically home to tumor tissue. In this study, two different peptides are introduced to synthetic dendritic scaffolds via oxime chemistry and the resulting compounds are analyzed for tumor homing. Modification of the dendritic wedge with a short, linear peptide that homes to clotted plasma proteins showed that a specific receptor in tumor tissue is recognized, but that the extravasation is likely affected by the size of the construct. In contrast, a positively charged cyclic peptide with cell penetrating properties was capable of directing the entire dendritic architecture toward a specific receptor in tumor lymphatics. These observations are in agreement with results previously reported for micelles and nanoparticles and emphasize the influence of peptide properties and overall size on the biodistribution of multivalent macromolecules.