Chemistry at the Nano−Bio Interface

The interface of biology and inorganic materials represents one of the fastest growing and most promising areas of nanotechnology. The fifth issue of JACS Select contains 22 Communications and Articles from 2008 and early 2009 that illustrate the breadth and creative energy of this young field. Although the use of colloidal particles of metals and semiconductors as pigments dates back many centuries, and although the recipe for stable 6 nm diameter particles of gold (“Ruby gold”) was famously devised by Faraday in 1857, the unique properties of nanomaterials and their promise for applications in biochemistry, cell biology, and medicine have only recently been appreciated. Prior to the 1990s, the principal role of inorganic colloids in biological research was as high-contrast stains for electron microscopy. A paradigm shift occurred in 1996, when Mirkin, Alivisatos, and co-workers coupled metal nanoparticles to DNA. Their experiments demonstrated not only that DNA could be used for the organization of nanostructures, as had been suggested in earlier experiments by Seeman, but also that nanoparticles were highly sensitive spectroscopic reporters for the base-pairing of DNA. Advances in the synthesis of crystalline, size-selected, and epitaxially capped semiconductor quantum dots early in the 1990s set the stage for their conjugation to antibodies that could target them to specific biological molecules in cells. These experiments demonstrated that brightly luminescent quantum dots were effective for intracellular imaging and were potentially competitive in that role with fluorescent molecules and proteins. Almost simultaneously, techniques were devised for controlling the size and understanding the magnetic behavior of transition metal oxide and magnetic alloy nanoparticles. By the end of the 1990s, bioconjugated magnetic nanoparticles were used for sophisticated imaging experiments as well as for the targeted destruction of cancer cells. Carbon nanotubes were discovered in the early 1990s, and versatile techniques were also developed for growing semiconductor nanowires. Nanotubes and nanowires, because of their extreme aspect ratio and sensitivity to charge-transfer interactions, proved to be very sensitive platforms for the detection of biomolecules. Research in the current decade has led to a much more sophisticated set of tools for controlling the size, shape, dispersity, and surface chemistry of nanoparticles. The complexity of nanoparticle structures s as nanoshells, prisms, Janus particles, derivatized nanotubes, core-shell particles, and striped nanowires, to name a few s offers new tools to tailor particles to specific problems in ultratrace detection, imaging, drug delivery, DNA/RNA delivery, and therapy. Sophisticated schemes for signal amplification, enhanced bioaffinity through multivalency, and cooperative binding highlight the synergy of nanoparticles as platforms for biological molecular recognition. The deliberate design of nanoparticles for biological applications, for example for drug delivery or for dual functions (such as imaging and magnetic manipulation of cells), has been enabled by these new advances in nanoparticle synthesis. In addition, nanoparticles and nanotubes, when properly functionalized, can be used as effective vehicles for controllable generation of