Fluorescein- and EGFR-Antibody Conjugated Silica Nanoparticles for Enhancement of Real-time Tumor Border Definition Using Confocal Laser Endomicroscopy in Squamous Cell Carcinoma of the Head and Neck
Anna Watermann,
Rita Gieringer,
Anna-Maria Bauer,
Sven Kurch,
Ralf Kiesslich,
Wolfgang Tremel,
Jan Gosepath,
Juergen Brieger
Affiliations
Anna Watermann
Molecular Tumorbiology, Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
Rita Gieringer
Molecular Tumorbiology, Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
Anna-Maria Bauer
Institute of Inorganic Chemistry and Analytical Chemistry, Johannes Gutenberg University, 55128 Mainz, Germany
Sven Kurch
Institute of Inorganic Chemistry and Analytical Chemistry, Johannes Gutenberg University, 55128 Mainz, Germany
Ralf Kiesslich
HSK Klinik für Innere Medizin II: Gastroenterologie, Hepatologie und Endokrinologie, 65199 Wiesbaden, Germany
Wolfgang Tremel
Institute of Inorganic Chemistry and Analytical Chemistry, Johannes Gutenberg University, 55128 Mainz, Germany
Jan Gosepath
HSK Klinik für Hals-, Nasen- und Ohrenheilkunde, Kopf- und Hals-Chirugie, 65199 Wiesbaden, Germany
Juergen Brieger
Molecular Tumorbiology, Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
Intraoperative definition of tumor free resection margins in head and neck cancer is challenging. In the current proof-of-principle study we evaluated a novel silica nanoparticle-based agent for its potential use as contrast enhancer. We synthesized silica nanoparticles with an average size of 45 nm and modified these particles with the fluorescence stain fluorescein isocyanate (FITC) for particle detection and with epidermal growth factor receptor (EGFR)-targeting antibodies for enhanced tumor specificity. The nanoparticles exhibited good biocompatibility and could be detected in vitro and in vivo by confocal laser scanning microscopy. Additionally, we show in an ex vivo setting that these modified nanoparticles specifically bind to tumor samples and could be detected using a handheld confocal fluorescence endomicroscope. From a clinical point of view, we believe that this method could be used for tumor border contrast enhancement and for better intraoperative definition of R-0 tumor resection.
