Enhanced EGFR Targeting Activity of Plasmonic Nanostructures with Engineered GE11 Peptide

Targeting activity is an important goal of nanomedicine and antibodies have been considered the natural molecules for such a task. However, their possible immunogenic activity and their cost have suggested finding other valid substitutes. Small molecules like peptides can be an alternative source of targeting agents, even if, as single molecules, their binding affinity is usually not as good as antibodies. GE11 is a small dodecapeptide that displays specific binding to the epidermal growth factor receptor (EGFR) and low mitogenic activity. The present work shows that an appropriate organization of thousands of PEG chains functionalized with GE11 on clusters of naked gold nanoparticles, obtained by laser ablation in water, achieves a better targeting activity than that recorded with nanoparticles decorated with the specific anti-EGFR antibody Cetuximab (C225), already used in the clinic. The insertion of a cationic spacer between the polymeric part of the ligand and the targeting peptide allows for a proper presentation of GE11 on the surface of the nanosystems, showing with very specific SERRS signals, the possibility of achieving, with colorectal cancer cells, at least 90% for sensitivity and specificity. Molecular dynamic calculations suggest that subtle differences in the exposition of the peptide on a PEG sea are important for the targeting activity.