Colloidal gold

Colloidal gold is a sol or colloidal suspension of nanoparticles of gold in a fluid, usually water. The colloid is coloured usually either wine red or blue-purple.
Due to their optical, electronic, and molecular-recognition properties, gold nanoparticles are the subject of substantial research, with many potential or promised applications in a wide variety of areas, including electron microscopy, electronics, nanotechnology, materials science, and biomedicine.
The properties of colloidal gold nanoparticles, and thus their potential applications, depend strongly upon their size and shape. For example, rodlike particles have both a transverse and longitudinal absorption peak, and anisotropy of the shape affects their self-assembly.

History

Used since ancient times as a method of staining glass, colloidal gold was used in the 4th-century Lycurgus Cup, which changes color depending on the location of light source.
During the Middle Ages, soluble gold, a solution containing gold salt, had a reputation for its curative property for various diseases. In 1618, Francis Anthony, a philosopher and member of the medical profession, published a book called Panacea Aurea, sive tractatus duo de ipsius Auro Potabili. The book introduces information on the formation of colloidal gold and its medical uses. About half a century later, English botanist Nicholas Culpepper published a book in 1656, Treatise of Aurum Potabile, solely discussing the medical uses of colloidal gold.
In 1676, Johann Kunckel, a German chemist, published a book on the manufacture of stained glass. In his book Valuable Observations or Remarks About the Fixed and Volatile Salts-Auro and Argento Potabile, Spiritu Mundi and the Like, Kunckel assumed that the pink color of Aurum Potabile came from small particles of metallic gold, not visible to human eyes. In 1842, John Herschel invented a photographic process called chrysotype that used colloidal gold to record images on paper.
Modern scientific evaluation of colloidal gold did not begin until Michael Faraday's work in the 1850s. In 1856, in a basement laboratory of Royal Institution, Faraday accidentally created a ruby red solution while mounting pieces of gold leaf onto microscope slides. Since he was already interested in the properties of light and matter, Faraday further investigated the optical properties of the colloidal gold. He prepared the first pure sample of colloidal gold, which he called 'divided gold', in 1857. He used phosphorus to reduce a solution of gold chloride. The colloidal gold Faraday made 150 years ago is still optically active. For a long time, the composition of the 'ruby' gold was unclear. Several chemists suspected it to be a gold tin compound, due to its preparation. Faraday recognized that the color was actually due to the miniature size of the gold particles. He noted the light scattering properties of suspended gold microparticles, which is now called Faraday-Tyndall effect.
In 1898, Richard Adolf Zsigmondy prepared the first colloidal gold in diluted solution. Apart from Zsigmondy, Theodor Svedberg, who invented ultracentrifugation, and Gustav Mie, who provided the theory for scattering and absorption by spherical particles, were also interested in the synthesis and properties of colloidal gold.
With advances in various analytical technologies in the 20th century, studies on gold nanoparticles has accelerated. Advanced microscopy methods, such as atomic force microscopy and electron microscopy, have contributed the most to nanoparticle research. Due to their comparably easy synthesis and high stability, various gold particles have been studied for their practical uses. Different types of gold nanoparticle are already used in many industries.

Physical properties

Optical

Colloidal gold has been used by artists for centuries because of the nanoparticle's interactions with visible light. Gold nanoparticles absorb and scatter light resulting in colours ranging from vibrant reds to blues to black and finally to clear and colorless, depending on particle size, shape, local refractive index, and aggregation state. These colors occur because of a phenomenon called localized surface plasmon resonance, in which conduction electrons on the surface of the nanoparticle oscillate in resonance with incident light.

Effect of size, shape, composition and environment

As a general rule, the wavelength of light absorbed increases as a function of increasing nanoparticle size. Both the surface plasmon resonance frequency and scattering intensity depend on the size, shape composition and environment of the nanoparticles. This phenomenon may be quantified by use of the Mie scattering theory for spherical nanoparticles. Nanoparticles with diameters of 30–100 nm may be detected easily by a microscope, and particles with a size of 40 nm may even be detected by the naked eye when the concentration of the particles is 10⁻⁴ M or greater. The scattering from a 60 nm nanoparticle is about 10⁵ times stronger than the emission from a fluorescein molecule.

Effect of local refractive index

Changes in the apparent color of a gold nanoparticle solution can also be caused by the environment in which the colloidal gold is suspended. The optical properties of gold nanoparticles depend on the refractive index near the nanoparticle surface, so the molecules directly attached to the nanoparticle surface and the nanoparticle solvent may both influence the observed optical features. As the refractive index near the gold surface increases, the LSPR shifts to longer wavelengths. In addition to solvent environment, the extinction peak can be tuned by coating the nanoparticles with non-conducting shells such as silica, biomolecules, or aluminium oxide.

Effect of aggregation

When gold nanoparticles aggregate, the optical properties of the particle change, because the effective particle size, shape, and dielectric environment all change.

Medical research

Electron microscope labelling

Colloidal gold and various derivatives have long been among the most widely used labels for antigens in biological electron microscopy. Colloidal gold particles can be attached to many traditional biological probes such as antibodies, lectins, superantigens, glycans, nucleic acids, and receptors. Particles of different sizes are easily distinguishable in electron micrographs, allowing simultaneous multiple-labelling experiments.
In addition to biological probes, gold nanoparticles can be transferred to various mineral substrates, such as mica, single crystal silicon, and atomically flat gold, to be observed under atomic force microscopy.

Drug delivery system

Gold nanoparticles can be used to optimize the biodistribution of drugs to diseased organs, tissues or cells, in order to improve and target drug delivery.
Nanoparticle-mediated drug delivery is feasible only if the drug distribution is otherwise inadequate. These cases include drug targeting of unstable, delivery to the difficult sites and drugs with serious side effects. The performance of the nanoparticles depends on the size and surface functionalities in the particles. Also, the drug release and particle disintegration can vary depending on the system. An optimal nanodrug delivery system ensures that the active drug is available at the site of action for the correct time and duration, and their concentration should be above the minimal effective concentration and below the minimal toxic concentration.
Gold nanoparticles are being investigated as carriers for drugs such as Paclitaxel. The administration of hydrophobic drugs require molecular encapsulation and it is found that nanosized particles are particularly efficient in evading the reticuloendothelial system.

Tumor detection

In cancer research, colloidal gold can be used to target tumors and provide detection using SERS in vivo. These gold nanoparticles are surrounded with Raman reporters, which provide light emission that is over 200 times brighter than quantum dots. It was found that the Raman reporters were stabilized when the nanoparticles were encapsulated with a thiol-modified polyethylene glycol coat. This allows for compatibility and circulation in vivo. To specifically target tumor cells, the polyethylenegylated gold particles are conjugated with an antibody, against, e.g. epidermal growth factor receptor, which is sometimes overexpressed in cells of certain cancer types. Using SERS, these pegylated gold nanoparticles can then detect the location of the tumor.
Gold nanoparticles accumulate in tumors, due to the leakiness of tumor vasculature, and can be used as contrast agents for enhanced imaging in a time-resolved optical tomography system using short-pulse lasers for skin cancer detection in mouse model. It is found that intravenously administered spherical gold nanoparticles broadened the temporal profile of reflected optical signals and enhanced the contrast between surrounding normal tissue and tumors.

Gene therapy

Gold nanoparticles have shown potential as intracellular delivery vehicles for siRNA oligonucleotides with maximal therapeutic impact.
Gold nanoparticles show potential as intracellular delivery vehicles for antisense oligonucleotides by providing protection against intracellular nucleases and ease of functionalization for selective targeting.

Photothermal agents

are being investigated as photothermal agents for in-vivo applications. Gold nanorods are rod-shaped gold nanoparticles whose aspect ratios tune the surface plasmon resonance band from the visible to near-infrared wavelength. The total extinction of light at the SPR is made up of both absorption and scattering. For the smaller axial diameter nanorods, absorption dominates, whereas for the larger axial diameter nanorods scattering can dominate. As a consequence, for in-vivo studies, small diameter gold nanorods are being used as photothermal converters of near-infrared light due to their high absorption cross-sections. Since near-infrared light transmits readily through human skin and tissue, these nanorods can be used as ablation components for cancer, and other targets. When coated with polymers, gold nanorods have been observed to circulate in-vivo with half-lives longer than 6 hours, bodily residence times around 72 hours, and little to no uptake in any internal organs except the liver.
Despite the unquestionable success of gold nanorods as photothermal agents in preclinical research, they have yet to obtain the approval for clinical use because the size is above the renal excretion threshold. In 2019, the first NIR-absorbing plasmonic ultrasmall-in-nano architecture has been reported, and jointly combine: a suitable photothermal conversion for hyperthermia treatments, the possibility of multiple photothermal treatments and renal excretion of the building blocks after the therapeutic action.