Targeting Metastatic Oral Cancer with Dual-Modal Metallic Nanoparticles

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DESCRIPTION (provided by applicant): Squamous cell carcinomas (SCC) encompass 90% of oral malignancies, which are the eighth most common cancer worldwide. Even with recent advances in oncology and surgery, mortality rates remain high. Often, end stage fatality is associated with the process of metastasis, where malignant cells invade the local basement membrane and move to secondary sites. Therefore, specific detection and destruction of metastatic cells and processes are important goals in undermining the morbidity caused by oral SCC. This research seeks to provide diagnosis and treatment of metastatic oral SCC with metallic nanoparticles functionalized with synthetic polymers containing metal-binding and cancer-targeting motifs. Metal-binding peptides inspired by macromolecular adhesives used by the mussel and barnacle will be employed for immobilizing a polymer linked to cancer-targeting structures to facilitate binding to gold and silver nanocrystals. Antibodies for the epidermal growth factor receptor (EGFR), a current clinical biomarker and over expressed in as many as 80% of oral, head, and neck SCCs, will be used as the targeting structure. Potentially, other cancer biomarkers such as cell surface peptides specific to oral SCC, the CXCR4 chemokine receptor, and glucose transporters could be targeted with the same adhesive scheme to increase specificity of metastatic phenotype targeting schemes. Anti-EGFR antibodies and metal-binding peptides will be linked to polyethylene glycol (PEG) polymers and used to form EGFR-targeting metallic nanoparticles. Their surface plasmon resonance will be tuned into the near-infrared (NIR), a region well suited to oral SCC because of accessibility to conventional and fiber optic technology in clinical use, through control over the shape, size, and composition of the metallic crystals. In vitro targeting experiments will be performed with these dual-modal (diagnostic and therapeutic) plasmonic agents on SCC4, SSC15, and SSC25 cell lines, where the metallic nanoparticles will act as optical contrast and photothermal therapeutic agents in a confocal microscope imaging system. More specifically, this proposal will seek to achieve imaging and photothermal ablation of individual, metastatic cells, a goal that if met could lead to clinical treatment modalities, where surgeons could identify and ablate high-risk cells with a single vehicle.