Gold, enigmatically represented by the target-like design of its ancient alchemical symbol, has been considered a mystical material of great value for centuries. Nanoscale particles of gold now command a great deal of attention for biomedical applications. Depending on their size, shape, degree of aggregation, and local environment, gold nanoparticles can appear red, blue, or other colors. These visible colors reflect the underlying coherent oscillations of conduction-band electrons ("plasmons") upon irradiation with light of appropriate wavelengths. These plasmons underlie the intense absorption and elastic scattering of light, which in turn forms the basis for many biological sensing and imaging applications of gold nanoparticles. The brilliant elastic light-scattering properties of gold nanoparticles are sufficient to detect individual nanoparticles in a visible light microscope with approximately 10(2) nm spatial resolution. Despite the great excitement about the potential uses of gold nanoparticles for medical diagnostics, as tracers, and for other biological applications, researchers are increasingly aware that potential nanoparticle toxicity must be investigated before any in vivo applications of gold nanoparticles can move forward. In this Account, we illustrate the importance of surface chemistry and cell type for interpretation of nanoparticle cytotoxicity studies. We also describe a relatively unusual live cell application with gold nanorods. The light-scattering properties of gold nanoparticles, as imaged in dark-field optical microscopy, can be used to infer their positions in a living cell construct. Using this positional information, we can quantitatively measure the deformational mechanical fields associated with living cells as they push and pull on their local environment. The local mechanical environment experienced by cells is part of a complex feedback loop that influences cell metabolism, gene expression, and migration.

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In this Feature Article, we examine recent advances in chemical analyte detection and optical imaging applications using gold and silver nanoparticles, with a primary focus on our own work. Noble metal nanoparticles have exciting physical and chemical properties that are entirely different from the bulk. For chemical sensing and imaging, the optical properties of metallic nanoparticles provide a wide range of opportunities, all of which ultimately arise from the collective oscillations of conduction band electrons ("plasmons") in response to external electromagnetic radiation. Nanorods have multiple plasmon bands compared to nanospheres. We identify four optical sensing and imaging modalities for metallic nanoparticles: (1) aggregation-dependent shifts in plasmon frequency; (2) local refractive index-dependent shifts in plasmon frequency; (3) inelastic (surface-enhanced Raman) light scattering; and (4) elastic (Rayleigh) light scattering. The surface chemistry of the nanoparticles must be tunable to create chemical specificity, and is a key requirement for successful sensing and imaging platforms.

Gold nanorods exhibit optical properties that are tunable with their shape, leading to sensing, imaging, and biomedical therapeutic applications. Colloidal preparations of gold nanorods impart surfactants or other species on the nanorod surfaces; a popular preparation leads to a surfactant bilayer on the surface. The specific chemistry at three distinct interfaces has roles to play in the growth and subsequent usage of these nanomaterials; these interfaces are the gold−surfactant interface, the hydrophobic surfactant bilayer, and, finally, the surfactant interface with the aqueous bulk. Each one of these interfaces provides strategies for altering nanorod properties such as stability against aggregation, toxicity, and ease of assembly. It is the solvent-accessible interface that dictates nanorod interactions with other particles, macromolecules, and living cells.

We report the direct visualization of interactions between drug-loaded nanoparticles and the cancer cell nucleus. Nanoconstructs composed of nucleolin-specific aptamers and gold nanostars were actively transported to the nucleus and induced major changes to the nuclear phenotype via nuclear envelope invaginations near the site of the construct. The number of local deformations could be increased by ultra-fast, light-triggered release of the aptamers from the surface of the gold nanostars. Cancer cells with more nuclear envelope folding showed increased caspase 3 and 7 activity (apoptosis) as well as decreased cell viability. This newly revealed correlation between drug-induced changes in nuclear phenotype and increased therapeutic efficacy could provide new insight for nuclear-targeted cancer therapy.