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.

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.

Increases in the prevalence of antibiotic resistant bacteria require new approaches for the treatment of infectious bacterial pathogens. It is now clear that a nanotechnology-driven approach using nanoparticles to selectively target and destroy pathogenic bacteria can be successfully implemented. We have explored this approach by using gold nanorods that have been covalently linked to primary antibodies to selectively destroy the pathogenic Gram-negative bacterium, Pseudomonas aeruginosa. We find that, following nanorod attachment to the bacterial cell surface, exposure to near-infrared radiation results in a significant reduction in bacterial cell viability.

Understanding plant interactions with nanoparticles is of increasing importance for assessing their toxicity and trophic transport. The primary objective of this study was to assess uptake, biodistribution and toxicity associated with exposure of tobacco plants (Nicotiana xanthi) to gold nanoparticles (AuNPs). We employed synchrotron-based X-ray microanalysis with X-ray absorption near-edge microspectroscopy and high resolution electron microscopy to localize AuNPs within plants. Results from these experiments reveal that AuNPs entered plants through the roots and moved into the vasculature. Aggregate bodies were also detected within root cell cytoplasm. Furthermore, AuNP uptake was size selective as 3.5 nm AuNP spheres were detected in plants but 18 nm AuNPs remained agglomerated on the root outer surfaces. Finally, leaf necrosis was observed after 14 days of exposure to 3.5 nm AuNPs. Overall, results of this work show the potential for AuNPs to enter plants through size-dependent mechanisms, translocate to cells and tissues and cause biotoxicity.

In biological tissue, complex mechanisms of cellular response are closely linked to the mechanical environment that cells experience. The key to understanding these mechanisms may lie in measurement of local mechanical fields near living cells and between cells. We have developed a novel optical measurement technique which combines the light elastically scattered from gold nanorods with digital image analysis to track local deformations that occur in vitro between cells, in real time, under darkfield optical microscopy. We find that measurable tension and compression exist in the intercellular matrix at the length scale of micrometers, as the cells assess, adapt, and rearrange their environment.