Enhanced EGFR Targeting Activity of Plasmonic Nanostructures with Engineered GE11 Peptide

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  • Francesca Biscaglia
    Department of Chemical Sciences University of Padova Via Marzolo 1 35131 Padova Italy
  • Senthilkumar Rajendran
    Department of Surgery Oncology and Gastroenterology University of Padova Via Giustiniani, 2 35124 Padova Italy
  • Paolo Conflitti
    Department of Chemical Sciences & Technologies University of Roma Tor Vergata and CSGI Via della Ricerca Scientifica 00133 Rome Italy
  • Clara Benna
    Department of Surgery Oncology and Gastroenterology University of Padova Via Giustiniani, 2 35124 Padova Italy
  • Roberta Sommaggio
    Department of Surgery Oncology and Gastroenterology University of Padova Via Giustiniani, 2 35124 Padova Italy
  • Lucio Litti
    Department of Chemical Sciences University of Padova Via Marzolo 1 35131 Padova Italy
  • Simone Mocellin
    Department of Surgery Oncology and Gastroenterology University of Padova Via Giustiniani, 2 35124 Padova Italy
  • Gianfranco Bocchinfuso
    Department of Chemical Sciences & Technologies University of Roma Tor Vergata and CSGI Via della Ricerca Scientifica 00133 Rome Italy
  • Antonio Rosato
    Department of Surgery Oncology and Gastroenterology University of Padova Via Giustiniani, 2 35124 Padova Italy
  • Antonio Palleschi
    Department of Chemical Sciences & Technologies University of Roma Tor Vergata and CSGI Via della Ricerca Scientifica 00133 Rome Italy
  • Donato Nitti
    Department of Surgery Oncology and Gastroenterology University of Padova Via Giustiniani, 2 35124 Padova Italy
  • Marina Gobbo
    Department of Chemical Sciences University of Padova Via Marzolo 1 35131 Padova Italy
  • Moreno Meneghetti
    Department of Chemical Sciences University of Padova Via Marzolo 1 35131 Padova Italy

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<jats:title>Abstract</jats:title><jats:p>Plasmonic nanostructures show important properties for biotechnological applications, but they have to be guided on the target for exploiting their potentialities. Antibodies are the natural molecules for targeting. However, their possible adverse 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 very good. GE11 is a small dodecapeptide with specific binding to the epidermal growth factor receptor (EGFR) and low immunogenicity. The present work shows that thousands of polyethylene glycol (PEG) chains modified with lysines and 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). The insertion of the 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. Surface enhanced resonance Raman scattering signals of the plasmonic gold nanoparticles are used for quantifying the targeting activity. Molecular dynamic calculations suggest that subtle differences in the exposition of the peptide on the PEG sea are important for the targeting activity.</jats:p>

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