Gold-Based Therapeutic Agents: A New Perspective

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.

Medicinal inorganic chemistry can exploit the unique properties of metal ions for the design of new drugs. This has, for instance, led to the clinical application of chemotherapeutic agents for cancer treatment, such as cisplatin. The use of cisplatin is, however, severely limited by its toxic side-effects. This has spurred chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action. Recent trends in the field are discussed in this review. These include the more selective delivery and/or activation of cisplatin-related prodrugs and the discovery of new non-covalent interactions with the classical target, DNA. The use of the metal as scaffold rather than reactive centre and the departure from the cisplatin paradigm of activity towards a more targeted, cancer cell-specific approach, a major trend, are discussed as well. All this, together with the observation that some of the new drugs are organometallic complexes, illustrates that exciting times lie ahead for those interested in 'metals in medicine'.