The development of facile seeded growth syntheses for anisotropic gold nanoparticles (particularly gold nanorods) has spurred an interest in their optical properties and applications. The development of the first seeded growth synthesis for gold nanorods in 2001 was a transformative event, providing the first simple, convenient wet chemistry route to these nanomaterials. Over the past decade, the original seeded growth procedure has been the subject of further modifications that have continuously expanded researchers’ access to anisotropic gold nanoparticles. Recent modifications to the synthesis have improved synthetic control over gold nanorod aspect ratio, increased synthesis up to the gram scale, and provided the opportunity to tightly control the absolute dimensions of AuNRs. Despite these advances, the mechanism of gold nanorod growth in this synthesis remains poorly understood. Recent investigations into gold nanorod growth mechanisms have revealed the process to be unexpectedly complex, suggesting that many different reagents interact synergistically to promote shape control, and that growth of the AuNR core may proceed by complex processes, such as stochastic nanorod growth. Nevertheless, the advent of new in situ characterization techniques promises to shortly reveal new insights into gold nanorod core growth, and may inform further significant modifications, improving the efficiency and versatility of seeded growth synthesis. In this review, we recount the history of the seeded growth synthesis for gold nanorods, examine the impact of recent advances in this synthesis, and current investigations into the mechanism of gold nanorod growth.

Anisotropic (nonspherical) metal nanoparticles are of widespread research interest because changing the shape of metals at the nanoscale can provide access to materials with unique optical, electronic, and catalytic properties. The development of seeded growth syntheses has provided researchers unprecedented access to anisotropic metal nanocrystals (particularly, gold, silver, platinum, and palladium nanocrystals) with precisely controlled dimensions and crystallographic features. The mechanisms by which the various reagents present in seeded growth syntheses accomplish shape control, however, have yet to be fully elucidated. Recently, the role halide ions play in controlling metal nanocrystal shape has become a subject of particular interest. There are many ways in which the halide ions may direct the anisotropic growth of metal nanocrystals, including modulating the redox potentials of the metal ions, acting as face-specific capping agents, and/or controlling the extent of silver underpotential deposition at the nanocrystal surface. In this Perspective, we examine recent progress in elucidating and articulating the role halide ions play in seeded growth with particular emphasis on gold nanoparticles.

Since the late 1980s, researchers have prepared inorganic nanoparticles of many types--including elemental metals, metal oxides, metal sulfides, metal selenides, and metal tellurides--with excellent control over size and shape. Originally many researchers were primarily interested in exploring the quantum size effects predicted for such materials. Applications of inorganic nanomaterials initially centered on physics, optics, and engineering but have expanded to include biology. Many current nanomaterials can serve as biochemical sensors, contrast agents in cellular or tissue imaging, drug delivery vehicles, or even as therapeutics. In this Account we emphasize that the understanding of how nanomaterials will function in a biological system relies on the knowledge of the interface between biological systems and nanomaterials, the nano-bio interface. Gold nanoparticles can serve as excellent standards to understand more general features of the nano-bio interface because of its many advantages over other inorganic materials. The bulk material is chemically inert, and well-established synthetic methods allow researchers to control its size, shape, and surface chemistry. Gold's background concentration in biological systems is low, which makes it relatively easy to measure it at the part-per-billion level or lower in water. In addition, the large electron density of gold enables relatively simple electron microscopic experiments to localize it within thin sections of cells or tissue. Finally, gold's brilliant optical properties at the nanoscale are tunable with size, shape, and aggregation state and enable many of the promising chemical sensing, imaging, and therapeutic applications. Basic experiments with gold nanoparticles and cells include measuring the toxicity of the particles to cells in in vitro experiments. The species other than gold in the nanoparticle solution can be responsible for the apparent toxicity at a particular dose. Once the identity of the toxic agent in nanoparticle solutions is known, researchers can employ strategies to mitigate toxicity. For example, the surfactant used at high concentration in the synthesis (0.1 M) of gold nanorods remains on their surface in the form of a bilayer and can be toxic to certain cells at 200 nM concentrations. Several strategies can alleviate the toxic response. Polyelectrolyte layer-by-layer wrapping can cover up the surfactant bilayer, or researchers can exchange the surfactant with chemically similar molecules. Researchers can also replace the surfactant with a biocompatible thiol or use a polymerizable surfactant that can be "stitched" onto the nanorods and reduce its lability. In all these cases, however, proteins or other molecules from the cellular media cover the engineered surface of the nanoparticles, which can drastically change the charges and functional groups on the nanoparticle surface.

The synthesis of well-defined inorganic nanoparticles in colloidal solution, which evolved gradually from the 1950s onward, has now reached the point where applications in both the research world and the wider world can be realized. This Perspective explores some of the successes and still-remaining challenges in nanoparticle synthesis and ligand analysis, highlights selected work in the areas of biomedicine and energy conversion that are enabled by colloidal nanomaterials, and discusses technical barriers that need to be overcome by chemists and other scientists in order for nanotechnology to achieve its promise.

Investigating the adsorption process of proteins on nanoparticle surfaces is essential to understand how to control the biological interactions of functionalized nanoparticles. In this work, a library of spherical and rod-shaped gold nanoparticles (GNPs) was used to evaluate the process of protein adsorption to their surfaces. The binding of a model protein (bovine serum albumin, BSA) to GNPs as a function of particle shape, size, and surface charge was investigated. Two independent comparative analytical methods were used to evaluate the adsorption process: steady-state fluorescence quenching titration and affinity capillary electrophoresis (ACE). Although under favorable electrostatic conditions kinetic analysis showed a faster adsorption of BSA to the surface of cationic GNPs, equilibrium binding constant determinations indicated that BSA has a comparable binding affinity to all of the GNPs tested, regardless of surface charge. BSA was even found to adsorb strongly to GNPs with a pegylated/neutral surface. However, these fluorescence titrations suffer from significant interference from the strong light absorption of the GNPs. The BSA-GNP equilibrium binding constants, as determined by the ACE method, were 10(5) times lower than values determined using spectroscopic titrations. While both analytical methods could be suitable to determine the binding constants for protein adsorption to NP surfaces, both methods have limitations that complicate the determination of protein-GNP binding constants. The optical properties of GNPs interfere with Ka determinations by static fluorescence quenching analysis. ACE, in contrast, suffers from material compatibility issues, as positively charged GNPs adhere to the walls of the capillary during analysis. Researchers seeking to determine equilibrium binding constants for protein-GNP interactions should therefore utilize as many orthogonal techniques as possible to study a protein-GNP system.