SYNTHESIS AND BIOFUNCTIONALIZATION OF PLASMONIC NANOSTRUCTURES FOR EGFR-MARKED CANCER CELL TARGETING AND SERRS IMAGING

Plasmonic nanoparticles are increasingly utilized in biomedical applications including imaging, diagnostics and therapy. Gold nanoparticles (AuNP), besides displaying useful optical properties, possess a facile surface chemistry and absence of inherent toxicity, an essential requirement for biological application. AuNP can passively target tumors by the enhanced permeability and retention effect, but active targeting by proteins, peptides or small molecules, can further improve the pharmacokinetic and pharmacodynamics profiles of these multifunctional agents. The dodecapeptide YHWYGYTPQNVI (GE11) was recently identified as a specific ligand for the Epidermal Growth Factor Receptor, which is overexpressed in many types of cancer[1]. In the present work we have employed the enormous sensitivity of the Surface Enhanced Raman Spectroscopy [2] to study the targeting activity of GE11-functionalized plasmonic nanostructures on different types of tumor cells. Nanoparticles were prepared, without stabilizing molecules, by laser ablation of a gold target in water, functionalized with a SERRS reporter [3], and conjugated with a number of ligands: GE11, mPEG, and different PEG-GE11 conjugates. Nanoaggregates covered with PEG or with the monoclonal antibody Cetuximab were used as negative and positive control, respectively. Targeting of nanostructures to EGFR was checked by incubation with cancer cells expressing or not the receptor and recording the SERRS signals for each cell. The influence of different aspects for EGFR recognition, such as peptide orientation and exposure on the NP surface, will be presented.