Plasmonic Nanostructures and Applications

Gold nanoparticles with unique optical properties may be useful as biosensors in living whole cells. Using a simple and inexpensive technique, we recorded surface plasmon resonance (SPR) scattering images and SPR absorption spectra from both colloidal gold nanoparticles and from gold nanoparticles conjugated to monoclonal anti-epidermal growth factor receptor (anti-EGFR) antibodies after incubation in cell cultures with a nonmalignant epithelial cell line (HaCaT) and two malignant oral epithelial cell lines (HOC 313 clone 8 and HSC 3). Colloidal gold nanoparticles are found in dispersed and aggregated forms within the cell cytoplasm and provide anatomic labeling information, but their uptake is nonspecific for malignant cells. The anti-EGFR antibody conjugated nanoparticles specifically and homogeneously bind to the surface of the cancer type cells with 600% greater affinity than to the noncancerous cells. This specific and homogeneous binding is found to give a relatively sharper SPR absorption band with a red shifted maximum compared to that observed when added to the noncancerous cells. These results suggest that SPR scattering imaging or SPR absorption spectroscopy generated from antibody conjugated gold nanoparticles can be useful in molecular biosensor techniques for the diagnosis and investigation of oral epithelial living cancer cells in vivo and in vitro. The increasing availability of nanostructures with highly controlled optical properties in the nanometer size range has created widespread interest in their use in biotechnological systems for diagnostic application and biological imaging.1-2 Cellular imaging utilizing microscope techniques provides anatomic details of cells and tissue architecture important for cancer diagnostics and research. Currently used optical probes include chemiluminescent, fluorimetric, and colorimetric techniques. Markers attached to antibodies provide specific information about the presence of specific molecules. Quantum dots are widely used and studied for this application due to their unique size-dependent fluorescence properties. But potential human toxicity and cytotoxicity of the semiconductor material are two major problems for its in vitro and in vivo application. Colloidal gold nanoparticles have become an alternative consideration due to their ease of preparation, ready bioconjugation, and potential noncytotoxicity. Immunogold nanoparticles conjugated to antibodies have provided excellent detection qualities for cellular labeling using electron microscopy. Gold nanoparticles have the ability to resonantly scatter visible and near-infrared light upon the excitation of their surface plasmon oscillation. The scattering light intensity is extremely sensitive to the size and aggregation state of the particles. Preliminary studies have reported their use as contrast agents for biomedical imaging using confocal scanning optical microscopy, multiphoton plasmon resonance microscopy, optical coherence microscopy, and third-harmonic microscopy. Gold nanoparticles have several advantages for cellular imaging compared to other agents. They scatter light intensely and they are much brighter than chemical fluorophores. They do not photobleach and they can be easily detected in as low as 10-16 M concentration. Sokolov described the scattering of anti-EGFR/Au nanoparticles for cervical cancer when stimulated with a laser at single wavelength. Irradiation with a laser will only scatter light that is close to the laser wavelength used. Gold * Corresponding authors. Ivan El-Sayed: [email protected]. Tel: 415-353-2401, Fax: 415-353-2603; Mostafa El-Sayed: [email protected]. Tel: 404-894-0292. Fax: 404-894-0294. † University of California at San Francisco. ‡ Georgia Institute of Technology. NANO