HOME

TheInfoList



OR:

Colloidal gold is a
sol Sol or SOL may refer to: Astronomy * The Sun Currency * SOL Project, a currency project in France * French sol, or sou * Argentine sol * Bolivian sol, the currency of Bolivia from 1827 to 1864 * Peruvian sol, introduced in 1991 * Peruvian sol ...
or
colloidal suspension A colloid is a mixture in which one substance consisting of microscopically dispersed insoluble particles is suspended throughout another substance. Some definitions specify that the particles must be dispersed in a liquid, while others exte ...
of
nanoparticles A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 10 ...
of
gold Gold is a chemical element with the symbol Au (from la, aurum) and atomic number 79. This makes it one of the higher atomic number elements that occur naturally. It is a bright, slightly orange-yellow, dense, soft, malleable, and ductile ...
in a fluid, usually water. The colloid is usually either wine-red coloured (for spherical particles less than 100  nm) or blue/purple (for larger spherical particles or nanorods). Due to their
optical Optics is the branch of physics that studies the behaviour and properties of light, including its interactions with matter and the construction of instruments that use or detect it. Optics usually describes the behaviour of visible, ultravio ...
, 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 An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
,
electronics The field of electronics is a branch of physics and electrical engineering that deals with the emission, behaviour and effects of electrons using electronic devices. Electronics uses active devices to control electron flow by amplification ...
,
nanotechnology Nanotechnology, also shortened to nanotech, is the use of matter on an atomic, molecular, and supramolecular scale for industrial purposes. The earliest, widespread description of nanotechnology referred to the particular technological goal ...
, materials science, and
biomedicine Biomedicine (also referred to as Western medicine, mainstream medicine or conventional medicine)
. 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 Absorption may refer to: Chemistry and biology *Absorption (biology), digestion **Absorption (small intestine) *Absorption (chemistry), diffusion of particles of gas or liquid into liquid or solid materials *Absorption (skin), a route by which s ...
peak, and
anisotropy Anisotropy () is the property of a material which allows it to change or assume different properties in different directions, as opposed to isotropy. It can be defined as a difference, when measured along different axes, in a material's physic ...
of the shape affects their
self-assembly Self-assembly is a process in which a disordered system of pre-existing components forms an organized structure or pattern as a consequence of specific, local interactions among the components themselves, without external direction. When the ...
.


History

Used since ancient times as a method of staining glass colloidal gold was used in the 4th-century
Lycurgus Cup The Lycurgus Cup is a 4th-century Roman glass cage cup made of a dichroic glass, which shows a different colour depending on whether or not light is passing through it: red when lit from behind and green when lit from in front. It is the only ...
, which changes color depending on the location of light source. During the
Middle Ages In the history of Europe, the Middle Ages or medieval period lasted approximately from the late 5th to the late 15th centuries, similar to the post-classical period of global history. It began with the fall of the Western Roman Empire ...
, soluble gold, a solution containing gold salt, had a reputation for its curative property for various diseases. In 1618,
Francis Anthony Francis Anthony (16 April 1550 – 26 May 1623) was a 16th-century physician and chemist. His father, Derrick Anthony, was a goldsmith in London, employed in the jewel office of Queen Elizabeth. He attended the University of Cambridge, receivin ...
, a philosopher and member of the medical profession, published a book called ''Panacea Aurea, sive tractatus duo de ipsius Auro Potabili'' (Latin: gold potion, or two treatments of
potable Drinking water is water that is used in drink or food preparation; potable water is water that is safe to be used as drinking water. The amount of drinking water required to maintain good health varies, and depends on physical activity level, ag ...
gold). The book introduces information on the formation of colloidal gold and its medical uses. About half a century later, English botanist Nicholas Culpepper published 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 Sir John Frederick William Herschel, 1st Baronet (; 7 March 1792 – 11 May 1871) was an English polymath active as a mathematician, astronomer, chemist, inventor, experimental photographer who invented the blueprint and did botanical wo ...
invented a photographic process called chrysotype (from the Greek χρῡσός meaning "gold") 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 The Royal Institution of Great Britain (often the Royal Institution, Ri or RI) is an organisation for scientific education and research, based in the City of Westminster. It was founded in 1799 by the leading British scientists of the age, inc ...
, 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 'activated gold', in 1857. He used
phosphorus Phosphorus is a chemical element with the symbol P and atomic number 15. Elemental phosphorus exists in two major forms, white phosphorus and red phosphorus, but because it is highly reactive, phosphorus is never found as a free element on Ea ...
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 Scattering is a term used in physics to describe a wide range of physical processes where moving particles or radiation of some form, such as light or sound, are forced to deviate from a straight trajectory by localized non-uniformities (including ...
properties of suspended gold microparticles, which is now called Faraday-Tyndall effect. In 1898,
Richard Adolf Zsigmondy Richard Adolf Zsigmondy ( hu, Zsigmondy Richárd Adolf; 1 April 1865 – 23 September 1929) was an Austrian-born chemist. He was known for his research in colloids, for which he was awarded the Nobel Prize in chemistry in 1925, as well as for c ...
prepared the first colloidal gold in diluted solution. Apart from Zsigmondy,
Theodor Svedberg Theodor Svedberg (30 August 1884 – 25 February 1971) was a Swedish chemist and Nobel laureate for his research on colloids and proteins using the ultracentrifuge. Svedberg was active at Uppsala University from the mid 1900s to late 1940s. ...
, who invented ultracentrifugation, and
Gustav Mie Gustav Adolf Feodor Wilhelm Ludwig Mie (; 29 September 1868 – 13 February 1957) was a German physicist. Life Mie was born in Rostock, Mecklenburg-Schwerin, Germany in 1868. From 1886 he studied mathematics and physics at the University of ...
, 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 Atomic force microscopy (AFM) or scanning force microscopy (SFM) is a very-high-resolution type of scanning probe microscopy (SPM), with demonstrated resolution on the order of fractions of a nanometer, more than 1000 times better than the opt ...
and
electron microscopy An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
, 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, such as electronics.


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 (smaller particles) to blues to black and finally to clear and colorless (larger particles), depending on particle size, shape, local refractive index, and aggregation state. These colors occur because of a phenomenon called localized surface plasmon resonance (LSPR), in which conduction electrons on the surface of the nanoparticle oscillate in resonance with incident light.


Effect of size

As a general rule, the wavelength of light absorbed increases as a function of increasing nano particle size. For example, pseudo-spherical gold nanoparticles with diameters ~ 30 nm have a peak LSPR absorption at ~530 nm.


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 depends on the refractive index near the nanoparticle surface, therefore both the molecules directly attached to the nanoparticle surface (i.e. nanoparticle ligands) and/or the nanoparticle
solvent A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
both may influence observed optical features. As the refractive index near the gold surface increases, the NP LSPR will shift 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, bio molecules, or aluminium oxide.


Effect of aggregation

When gold nano particles aggregate, the optical properties of the particle change, because the effective particle size, shape, and
dielectric In electromagnetism, a dielectric (or dielectric medium) is an electrical insulator that can be polarised by an applied electric field. When a dielectric material is placed in an electric field, electric charges do not flow through the ma ...
environment all change.


Medical research


Electron microscopy

Colloidal gold and various derivatives have long been among the most widely used labels for antigens in biological
electron microscopy An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
. Colloidal gold particles can be attached to many traditional biological probes such as
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
,
lectin Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides. Lectins have a role in rec ...
s,
superantigen Superantigens (SAgs) are a class of antigens that result in excessive activation of the immune system. Specifically it causes non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release. SAgs are ...
s,
glycan The terms glycans and polysaccharides are defined by IUPAC as synonyms meaning "compounds consisting of a large number of monosaccharides linked glycosidically". However, in practice the term glycan may also be used to refer to the carbohydrate ...
s,
nucleic acid Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main ...
s, 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(III), to be observed under atomic force microscopy (AFM).


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 (
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s, siRNA, DNA), delivery to the difficult sites (brain, retina, tumors, intracellular organelles) and drugs with serious side effects (e.g. anti-cancer agents). 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 (e.g. biodegradable polymers sensitive to pH). 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 (MEC) and below the minimal toxic concentration (MTC). Gold nanoparticles are being investigated as carriers for drugs such as
Paclitaxel Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical ca ...
. The administration of hydrophobic drugs require molecular encapsulation and it is found that nanosized particles are particularly efficient in evading the
reticuloendothelial system In anatomy the term "reticuloendothelial system" (abbreviated RES), often associated nowadays with the mononuclear phagocyte system (MPS), was originally launched by the beginning of the 20th century to denote a system of specialised cells that eff ...
.


Tumor detection

In cancer research, colloidal gold can be used to target tumors and provide detection using SERS ( surface enhanced Raman spectroscopy) ''in vivo''.These gold nanoparticles are surrounded with Raman reporters, which provide light emission that is over 200 times brighter than
quantum dots Quantum dots (QDs) are semiconductor particles a few nanometres in size, having optical and electronic properties that differ from those of larger particles as a result of quantum mechanics. They are a central topic in nanotechnology. When the ...
.It was found that the Raman reporters were stabilized when the nanoparticles were encapsulated with a thiol-modified
polyethylene glycol Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular we ...
coat.This allows for compatibility and circulation ''in vivo''.To specifically target tumor cells, the
polyethylene Polyethylene or polythene (abbreviated PE; IUPAC name polyethene or poly(methylene)) is the most commonly produced plastic. It is a polymer, primarily used for packaging ( plastic bags, plastic films, geomembranes and containers including b ...
gylated gold particles are conjugated with an antibody (or an antibody fragment such as scFv), against, e.g.
epidermal growth factor receptor The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands. The epidermal growth factor re ...
, 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 administrated 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 In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context ...
oligonucleotides (single and double stranded DNA) by providing protection against intracellular nucleases and ease of functionalization for selective targeting.


Photothermal agents

Gold nanorods In nanotechnology, nanorods are one morphology of nanoscale objects. Each of their dimensions range from 1–100 nm. They may be synthesized from metals or semiconducting materials. Standard aspect ratios (length divided by width) are 3-5. Na ...
are being investigated as photothermal agents for in-vivo applications.
Gold nanorods In nanotechnology, nanorods are one morphology of nanoscale objects. Each of their dimensions range from 1–100 nm. They may be synthesized from metals or semiconducting materials. Standard aspect ratios (length divided by width) are 3-5. Na ...
are rod-shaped gold nanoparticles whose aspect ratios tune the surface plasmon resonance (SPR) 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 (~10 nm), absorption dominates, whereas for the larger axial diameter nanorods (>35 nm) 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 In drug development, preclinical development, also termed preclinical studies or nonclinical studies, is a stage of research that begins before clinical trials (testing in humans) and during which important feasibility, iterative testing and drug ...
, 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 In physics, a plasmon is a quantum of plasma oscillation. Just as light (an optical oscillation) consists of photons, the plasma oscillation consists of plasmons. The plasmon can be considered as a quasiparticle since it arises from the quantiz ...
ultrasmall-in-nano architecture has been reported, and jointly combine: (i) a suitable photothermal conversion for
hyperthermia Hyperthermia, also known simply as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extrem ...
treatments, (ii) the possibility of multiple photothermal treatments and (iii) renal excretion of the building blocks after the therapeutic action.


Radiotherapy dose enhancer

Considerable interest has been shown in the use of gold and other heavy-atom-containing nanoparticles to enhance the dose delivered to tumors. Since the gold nanoparticles are taken up by the tumors more than the nearby healthy tissue, the dose is selectively enhanced. The biological effectiveness of this type of therapy seems to be due to the local deposition of the radiation dose near the nanoparticles. This mechanism is the same as occurs in
heavy ion therapy Particle therapy is a form of external beam radiotherapy using beams of energetic neutrons, protons, or other heavier positive ions for cancer treatment. The most common type of particle therapy as of August 2021 is proton therapy. In contra ...
.


Detection of toxic gas

Researchers have developed simple inexpensive methods for on-site detection of
hydrogen sulfide Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is poisonous, corrosive, and flammable, with trace amounts in ambient atmosphere having a characteristic foul odor of rotten eggs. The under ...
present in air based on the antiaggregation of gold nanoparticles (AuNPs). Dissolving into a weak
alkali In chemistry, an alkali (; from ar, القلوي, al-qaly, lit=ashes of the saltwort) is a basic, ionic salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as a base that dissolves in water. A solution of a ...
ne buffer solution leads to the formation of HS-, which can stabilize AuNPs and ensure they maintain their red color allowing for visual detection of toxic levels of .


Gold nanoparticle based biosensor

Gold nanoparticles are incorporated into
biosensor A biosensor is an analytical device, used for the detection of a chemical substance, that combines a biological component with a physicochemical detector. The ''sensitive biological element'', e.g. tissue, microorganisms, organelles, cell rece ...
s to enhance its stability, sensitivity, and selectivity. Nanoparticle properties such as small size, high surface-to-volume ratio, and high surface energy allow immobilization of large range of biomolecules. Gold nanoparticle, in particular, could also act as "electron wire" to transport electrons and its amplification effect on electromagnetic light allows it to function as signal amplifiers. Main types of gold nanoparticle based biosensors are optical and electrochemical biosensor.


Optical biosensor

Gold nanoparticles improve the sensitivity of optical sensor by response to the change in local refractive index. The angle of the incidence light for surface plasmon resonance, an interaction between light wave and conducting electrons in metal, changes when other substances are bounded to the metal surface. Because gold is very sensitive to its surroundings' dielectric constant, binding of an analyte would significantly shift gold nanoparticle's SPR and therefore allow more sensitive detection. Gold nanoparticle could also amplify the SPR signal. When the plasmon wave pass through the gold nanoparticle, the charge density in the wave and the electron I the gold interacted and resulted in higher energy response, so called electron coupling. Since the analyte and bio-receptor now bind to the gold, it increases the apparent mass of the analyte and therefore amplified the signal. These properties had been used to build DNA sensor with 1000-fold sensitive than without the Au NP. Humidity sensor was also built by altering the atom interspacing between molecules with humidity change, the interspacing change would also result in a change of the Au NP's LSPR.


Electrochemical biosensor

Electrochemical sensor convert biological information into electrical signals that could be detected. The conductivity and biocompatibility of Au NP allow it to act as "electron wire". It transfers electron between the electrode and the active site of the enzyme. It could be accomplished in two ways: attach the Au NP to either the enzyme or the electrode. GNP-glucose oxidase monolayer electrode was constructed use these two methods. The Au NP allowed more freedom in the enzyme's orientation and therefore more sensitive and stable detection. Au NP also acts as immobilization platform for the enzyme. Most biomolecules denatures or lose its activity when interacted with the electrode. The biocompatibility and high surface energy of Au allow it to bind to a large amount of protein without altering its activity and results in a more sensitive sensor. Moreover, Au NP also catalyzes biological reactions. Gold nanoparticle under 2 nm has shown
catalytic activity Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
to the oxidation of styrene.


Immunological biosensor

Gold nanoparticles have been coated with
peptides Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...
and glycans for use in immunological detection methods. The possibility to use glyconanoparticles in
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
was unexpected, but the method seems to have a high sensitivity and thus offers potential for development of specific assays for
diagnostic Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine "cause and effect". In systems enginee ...
identification of
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
in patient sera


Thin films

Gold nanoparticles capped with organic ligands, such as alkanethiol molecules, can self-assemble into large monolayers (>cm^). The particles are first prepared in organic solvent, such as chloroform or toluene, and are then spread into monolayers either on a liquid surface or on a solid substrate.Such interfacial thin films of nanoparticles have close relationship with Langmuir-Blodgett monolayers made from surfactants. The mechanical properties of nanoparticle monolayers have been studied extensively. For 5 nm spheres capped with dodecanethiol, the Young's modulus of the monolayer is on the order of GPa. The mechanics of the membranes are guided by strong interactions between ligand shells on adjacent particles. Upon fracture, the films crack perpendicular to the direction of strain at a fracture stress of 11 \pm 2.6 MPa, comparable to that of cross-linked polymer films. Free-standing nanoparticle membranes exhibit bending rigidity on the order of 10^ eV, higher than what is predicted in theory for continuum plates of the same thickness, due to nonlocal microstructural constraints such as nonlocal coupling of particle rotational degrees of freedom. On the other hand, resistance to bending is found to be greatly reduced in nanoparticle monolayers that are supported at the air/water interface, possibly due to screening of ligand interactions in a wet environment.


Surface chemistry

In many different types of colloidal gold syntheses, the
interface Interface or interfacing may refer to: Academic journals * ''Interface'' (journal), by the Electrochemical Society * '' Interface, Journal of Applied Linguistics'', now merged with ''ITL International Journal of Applied Linguistics'' * '' Int ...
of the nanoparticles can display widely different character – ranging from an interface similar to a
self-assembled monolayer Self-assembled monolayers (SAM) of organic molecules are molecular assemblies formed spontaneously on surfaces by adsorption and are organized into more or less large ordered domains. In some cases molecules that form the monolayer do not interact ...
to a disordered boundary with no repeating patterns. Beyond the Au-Ligand interface, conjugation of the interfacial ligands with various functional moieties (from small organic molecules to polymers to DNA to RNA) afford colloidal gold much of its vast functionality.


Ligand exchange/functionalization

After initial nanoparticle synthesis, colloidal gold ligands are often exchanged with new ligands designed for specific applications. For example, Au NPs produced via the Turkevich-style (or Citrate Reduction) method are readily reacted via ligand exchange reactions, due to the relatively weak binding between the carboxyl groups and the surfaces of the NPs. This ligand exchange can produce conjugation with a number of biomolecules from DNA to RNA to proteins to polymers (such as PEG) to increase
biocompatibility Biocompatibility is related to the behavior of biomaterials in various contexts. The term refers to the ability of a material to perform with an appropriate host response in a specific situation. The ambiguity of the term reflects the ongoing de ...
and functionality. For example, ligands have been shown to enhance
catalytic activity Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
by mediating interactions between adsorbates and the active gold surfaces for specific oxygenation reactions. Ligand exchange can also be used to promote phase transfer of the colloidal particles. Ligand exchange is also possible with alkane thiol-arrested NPs produced from the Brust-type synthesis method, although higher temperatures are needed to promote the rate of the ligand detachment. An alternative method for further functionalization is achieved through the conjugation of the ligands with other molecules, though this method can cause the colloidal stability of the Au NPs to breakdown.


Ligand removal

In many cases, as in various high-temperature catalytic applications of Au, the removal of the capping ligands produces more desirable physicochemical properties. The removal of ligands from colloidal gold while maintaining a relatively constant number of Au atoms per Au NP can be difficult due to the tendency for these bare clusters to aggregate. The removal of ligands is partially achievable by simply washing away all excess capping ligands, though this method is ineffective in removing all capping ligand. More often ligand removal achieved under high temperature or light
ablation Ablation ( la, ablatio – removal) is removal or destruction of something from an object by vaporization, chipping, erosive processes or by other means. Examples of ablative materials are described below, and include spacecraft material for ...
followed by washing. Alternatively, the ligands can be electrochemically etched off.


Surface structure and chemical environment

The precise structure of the ligands on the surface of colloidal gold NPs impact the properties of the colloidal gold particles. Binding conformations and surface packing of the capping ligands at the surface of the colloidal gold NPs tend to differ greatly from bulk surface model adsorption, largely due to the high curvature observed at the nanoparticle surfaces. Thiolate-gold interfaces at the nanoscale have been well-studied and the thiolate ligands are observed to pull Au atoms off of the surface of the particles to for “staple” motifs that have significant Thiyl-Au(0) character. The citrate-gold surface, on the other hand, is relatively less-studied due to the vast number of binding conformations of the citrate to the curved gold surfaces. A study performed in 2014 identified that the most-preferred binding of the citrate involves two carboxylic acids and the hydroxyl group of the citrate binds three surface metal atoms.


Health and safety

As gold nanoparticles (AuNPs) are further investigated for targeted drug delivery in humans, their toxicity needs to be considered. For the most part, it is suggested that AuNPs are biocompatible, but the concentrations at which they become toxic needs to be determined, and if those concentrations fall within the range of used concentrations. Toxicity can be tested ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...
'' and ''
in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and p ...
''. ''In vitro'' toxicity results can vary depending on the type of the cellular growth media with different protein compositions, the method used to determine cellular toxicity (cell health, cell stress, how many cells are taken into a cell), and the capping ligands in solution. ''In vivo'' assessments can determine the general health of an organism (abnormal behavior, weight loss, average life span) as well as tissue specific toxicology (kidney, liver, blood) and inflammation and oxidative responses. ''In vitro'' experiments are more popular than ''in vivo'' experiments because ''in vitro'' experiments are more simplistic to perform than ''in vivo'' experiments.


Toxicity and hazards in synthesis

While AuNPs themselves appear to have low or negligible toxicity, and the literature shows that the toxicity has much more to do with the ligands rather than the particles themselves, the synthesis of them involves chemicals that are hazardous.
Sodium borohydride Sodium borohydride, also known as sodium tetrahydridoborate and sodium tetrahydroborate, is an inorganic compound with the formula Na BH4. This white solid, usually encountered as an aqueous basic solution, is a reducing agent that finds applica ...
, a harsh reagent, is used to reduce the gold ions to gold metal. The gold ions usually come from
chloroauric acid Chloroauric acid is an inorganic compound with the chemical formula . It forms hydrates . Both the trihydrate and tetrahydrate are known. Both are orange-yellow solids consisting of the planar anion. Often chloroauric acid is handled as a soluti ...
, a potent acid. Because of the high toxicity and hazard of reagents used to synthesize AuNPs, the need for more “green” methods of synthesis arose.


Toxicity due to capping ligands

Some of the capping ligands associated with AuNPs can be toxic while others are nontoxic. In gold nanorods (AuNRs), it has been shown that a strong cytotoxicity was associated with CTAB-stabilized AuNRs at low concentration, but it is thought that free CTAB was the culprit in toxicity . Modifications that overcoat these AuNRs reduces this toxicity in human colon cancer cells (HT-29) by preventing CTAB molecules from desorbing from the AuNRs back into the solution. Ligand toxicity can also be seen in AuNPs. Compared to the 90% toxicity of HAuCl4 at the same concentration, AuNPs with carboxylate termini were shown to be non-toxic. Large AuNPs conjugated with biotin, cysteine, citrate, and glucose were not toxic in human leukemia cells ( K562) for concentrations up to 0.25 M. Also, citrate-capped gold nanospheres (AuNSs) have been proven to be compatible with human blood and did not cause platelet aggregation or an immune response. However, citrate-capped gold nanoparticles sizes 8-37 nm were found to be lethally toxic for mice, causing shorter lifespans, severe sickness, loss of appetite and weight, hair discoloration, and damage to the liver, spleen, and lungs; gold nanoparticles accumulated in the spleen and liver after traveling a section of the immune system. There are mixed-views for
polyethylene glycol Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular we ...
(PEG)-modified AuNPs. These AuNPs were found to be toxic in mouse liver by injection, causing cell death and minor inflammation. However, AuNPs conjugated with PEG copolymers showed negligible toxicity towards human colon cells ( Caco-2). AuNP toxicity also depends on the overall charge of the ligands. In certain doses, AuNSs that have positively-charged ligands are toxic in monkey kidney cells (Cos-1), human red blood cells, and E. coli because of the AuNSs interaction with the negatively-charged cell membrane; AuNSs with negatively-charged ligands have been found to be nontoxic in these species. In addition to the previously mentioned ''in vivo'' and ''in vitro'' experiments, other similar experiments have been performed. Alkylthiolate-AuNPs with trimethlyammonium ligand termini mediate the translocation of DNA across mammalian cell membranes ''in vitro'' at a high level, which is detrimental to these cells. Corneal haze in rabbits have been healed ''in vivo'' by using polyethylemnimine-capped gold nanoparticles that were transfected with a gene that promotes wound healing and inhibits corneal
fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...
.


Toxicity due to size of nanoparticles

Toxicity in certain systems can also be dependent on the size of the nanoparticle. AuNSs size 1.4 nm were found to be toxic in human skin cancer cells (SK-Mel-28), human cervical cancer cells (
HeLa HeLa (; also Hela or hela) is an immortalized cell line used in scientific research. It is the oldest and most commonly used human cell line. The line is derived from cervical cancer cells taken on February 8, 1951, named after Henrietta ...
), mouse
fibroblast A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells ...
cells (L929), and mouse
macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
(J774A.1), while 0.8, 1.2, and 1.8 nm sized AuNSs were less toxic by a six-fold amount and 15 nm AuNSs were nontoxic. There is some evidence for AuNP buildup after injection in ''in vivo'' studies, but this is very size dependent. 1.8 nm AuNPs were found to be almost totally trapped in the lungs of rats. Different sized AuNPs were found to buildup in the blood, brain, stomach, pancreas, kidneys, liver, and spleen.
Biosafety Biosafety is the prevention of large-scale loss of biological integrity, focusing both on ecology and human health. These prevention mechanisms include conduction of regular reviews of the biosafety in laboratory settings, as well as strict guide ...
and biokinetics investigations on biodegradable ultrasmall-in-nano architectures have demonstrated that gold nanoparticles are able to avoid metal accumulation in organisms through escaping by the renal pathway.


Synthesis

Generally, gold nanoparticles are produced in a liquid ("liquid chemical methods") by reduction of
chloroauric acid Chloroauric acid is an inorganic compound with the chemical formula . It forms hydrates . Both the trihydrate and tetrahydrate are known. Both are orange-yellow solids consisting of the planar anion. Often chloroauric acid is handled as a soluti ...
().To prevent the particles from aggregating, stabilizing agents are added.Citrate acts both as the reducing agent and colloidal stabilizer. They can be functionalized with various organic ligands to create organic-inorganic hybrids with advanced functionality.


Turkevich method

This simple method was pioneered by J. Turkevich et al. in 1951 and refined by G. Frens in the 1970s. It produces modestly monodisperse spherical gold nanoparticles of around 10–20 nm in diameter.Larger particles can be produced, but at the cost of monodispersity and shape. In this method, hot
chloroauric acid Chloroauric acid is an inorganic compound with the chemical formula . It forms hydrates . Both the trihydrate and tetrahydrate are known. Both are orange-yellow solids consisting of the planar anion. Often chloroauric acid is handled as a soluti ...
is treated with
sodium citrate Sodium citrate may refer to any of the sodium salts of citric acid (though most commonly the third): * Monosodium citrate * Disodium citrate * Trisodium citrate The three forms of salt are collectively known by the E number E331. Applications ...
solution, producing colloidal gold. The Turkevich reaction proceeds via formation of transient gold
nanowire A nanowire is a nanostructure in the form of a wire with the diameter of the order of a nanometre (10−9 metres). More generally, nanowires can be defined as structures that have a thickness or diameter constrained to tens of nanometers or less ...
s. These gold nanowires are responsible for the dark appearance of the reaction solution before it turns ruby-red.


Capping agents

A capping agent is used during nanoparticle synthesis to inhibit particle growth and aggregation. The chemical blocks or reduces reactivity at the periphery of the particle—a good capping agent has a high affinity for the new nuclei. Citrate ions or tannic acid function both as a reducing agent and a capping agent. Less sodium citrate results in larger particles.


Brust-Schiffrin method

This method was discovered by Brust and Schiffrin in the early 1990s, and can be used to produce gold nanoparticles in
organic liquid In chemistry, organic compounds are generally any chemical compounds that contain carbon- hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. T ...
s that are normally not
miscible Miscibility () is the property of two substances to mix in all proportions (that is, to fully dissolve in each other at any concentration), forming a homogeneous mixture (a solution). The term is most often applied to liquids but also applies ...
with water (like
toluene Toluene (), also known as toluol (), is a substituted aromatic hydrocarbon. It is a colorless, water-insoluble liquid with the smell associated with paint thinners. It is a mono-substituted benzene derivative, consisting of a methyl group (CH3) ...
). It involves the reaction of a
chlorauric acid Chloroauric acid is an inorganic compound with the chemical formula . It forms hydrates . Both the trihydrate and tetrahydrate are known. Both are orange-yellow solids consisting of the planar anion. Often chloroauric acid is handled as a solutio ...
solution with
tetraoctylammonium bromide Tetraoctylammonium bromide (TOAB or TOABr) is a quaternary ammonium compound with the chemical formula: H3(CH2)7sub>4 N Br. It is generally used as a phase transfer catalyst between an aqueous An aqueous solution is a solution in which the ...
(TOAB) solution in
toluene Toluene (), also known as toluol (), is a substituted aromatic hydrocarbon. It is a colorless, water-insoluble liquid with the smell associated with paint thinners. It is a mono-substituted benzene derivative, consisting of a methyl group (CH3) ...
and
sodium borohydride Sodium borohydride, also known as sodium tetrahydridoborate and sodium tetrahydroborate, is an inorganic compound with the formula Na BH4. This white solid, usually encountered as an aqueous basic solution, is a reducing agent that finds applica ...
as an anti-coagulant and a reducing agent, respectively. Here, the gold nanoparticles will be around 5–6 nm. NaBH4 is the reducing agent, and TOAB is both the
phase transfer catalyst In chemistry, a phase-transfer catalyst or PTC is a catalyst that facilitates the transition of a reactant from one phase into another phase where reaction occurs. Phase-transfer catalysis is a special form of heterogeneous catalysis. Ionic rea ...
and the stabilizing agent. TOAB does not bind to the gold nanoparticles particularly strongly, so the solution will aggregate gradually over the course of approximately two weeks. To prevent this, one can add a stronger binding agent, like a
thiol In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl gro ...
(in particular, alkanethiols), which will bind to gold, producing a near-permanent solution. Alkanethiol protected gold nanoparticles can be precipitated and then redissolved. Thiols are better binding agents because there is a strong affinity for the gold-sulfur bonds that form when the two substances react with each other. Tetra-dodecanthiol is a commonly used strong binding agent to synthesize smaller particles. Some of the phase transfer agent may remain bound to the purified nanoparticles, this may affect physical properties such as
solubility In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solubi ...
. In order to remove as much of this agent as possible, the nanoparticles must be further purified by soxhlet extraction.


Perrault method

This approach, discovered by Perrault and Chan in 2009, uses hydroquinone to reduce HAuCl4 in an aqueous solution that contains 15 nm gold nanoparticle seeds. This seed-based method of synthesis is similar to that used in photographic film development, in which silver grains within the film grow through addition of reduced silver onto their surface. Likewise, gold nanoparticles can act in conjunction with hydroquinone to catalyze reduction of ionic gold onto their surface. The presence of a stabilizer such as citrate results in controlled deposition of gold atoms onto the particles, and growth. Typically, the nanoparticle seeds are produced using the citrate method. The hydroquinone method complements that of Frens, as it extends the range of monodispersed spherical particle sizes that can be produced. Whereas the Frens method is ideal for particles of 12–20 nm, the hydroquinone method can produce particles of at least 30–300 nm.


Martin method

This simple method, discovered by Martin and Eah in 2010, generates nearly monodisperse "naked" gold nanoparticles in water. Precisely controlling the reduction stoichiometry by adjusting the ratio of NaBH4-NaOH ions to HAuCl4-HCl ions within the "sweet zone," along with heating, enables reproducible diameter tuning between 3–6 nm. The aqueous particles are colloidally stable due to their high charge from the excess ions in solution. These particles can be coated with various hydrophilic functionalities, or mixed with hydrophobic ligands for applications in non-polar solvents. In non-polar solvents the nanoparticles remain highly charged, and self-assemble on liquid droplets to form 2D monolayer films of monodisperse nanoparticles.


Nanotech studies

''Bacillus licheniformis'' can be used in synthesis of gold nanocubes with sizes between 10 and 100 nanometres. Gold nanoparticles are usually synthesized at high temperatures in organic solvents or using toxic reagents. The bacteria produce them in much milder conditions.


Navarro et al. method

For particles larger than 30 nm, control of particle size with a low polydispersity of spherical gold nanoparticles remains challenging. In order to provide maximum control on the NP structure, Navarro and co-workers used a modified Turkevitch-Frens procedure using sodium acetylacetonate as the reducing agent and sodium citrate as the stabilizer.


Sonolysis

Another method for the experimental generation of gold particles is by
sonolysis In chemistry, the study of sonochemistry is concerned with understanding the effect of ultrasound in forming acoustic cavitation in liquids, resulting in the initiation or enhancement of the chemical activity in the solution. Therefore, the chemica ...
. The first method of this type was invented by Baigent and Müller. This work pioneered the use of ultrasound to provide the energy for the processes involved and allowed the creation of gold particles with a diameter of under 10 nm. In another method using ultrasound, the reaction of an aqueous solution of HAuCl4 with
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
, the
reducing agent In chemistry, a reducing agent (also known as a reductant, reducer, or electron donor) is a chemical species that "donates" an electron to an (called the , , , or ). Examples of substances that are commonly reducing agents include the Earth met ...
s are hydroxyl radicals and sugar
pyrolysis The pyrolysis (or devolatilization) process is the thermal decomposition of materials at elevated temperatures, often in an inert atmosphere. It involves a change of chemical composition. The word is coined from the Greek-derived elements '' ...
radicals Radical may refer to: Politics and ideology Politics *Radical politics, the political intent of fundamental societal change *Radicalism (historical), the Radical Movement that began in late 18th century Britain and spread to continental Europe and ...
(forming at the interfacial region between the collapsing cavities and the bulk water) and the morphology obtained is that of nanoribbons with width 30–50 nm and length of several micrometers. These ribbons are very flexible and can bend with angles larger than 90°. When glucose is replaced by
cyclodextrin Cyclodextrins are a family of cyclic oligosaccharides, consisting of a macrocyclic ring of glucose subunits joined by α-1,4 glycosidic bonds. Cyclodextrins are produced from starch by enzymatic conversion. They are used in food, pharmaceutical ...
(a glucose oligomer), only spherical gold particles are obtained, suggesting that glucose is essential in directing the morphology toward a ribbon.


Block copolymer-mediated method

An economical, environmentally benign and fast synthesis methodology for gold nanoparticles using block copolymer has been developed by Sakai et al. In this synthesis methodology, block copolymer plays the dual role of a reducing agent as well as a stabilizing agent. The formation of gold nanoparticles comprises three main steps: reduction of gold salt ion by block copolymers in the solution and formation of gold clusters, adsorption of block copolymers on gold clusters and further reduction of gold salt ions on the surfaces of these gold clusters for the growth of gold particles in steps, and finally its stabilization by block copolymers. But this method usually has a limited-yield (nanoparticle concentration), which does not increase with the increase in the gold salt concentration. Ray et al. improved this synthesis method by enhancing the nanoparticle yield by manyfold at ambient temperature.


Applications


Antibiotic conjugated nanoparticle synthesis

Antibiotic functionalized metal nanoparticles have been widely studied as a mode to treat multi-drug resistant bacterial strains. For example, kanamycin capped gold-nanoparticles (Kan-AuPs) showed broad spectrum dose dependent antibacterial activity against both gram positive and gram negative bacterial strains in comparison to kanamycin alone.


See also

* Colloidal silver *
Gold nanorods In nanotechnology, nanorods are one morphology of nanoscale objects. Each of their dimensions range from 1–100 nm. They may be synthesized from metals or semiconducting materials. Standard aspect ratios (length divided by width) are 3-5. Na ...
* Gold nanoparticles in chemotherapy *
Nanozymes An artificial enzyme is a synthetic organic molecule or ion that recreates one or more functions of an enzyme. It seeks to deliver catalysis at rates and selectivity observed in naturally occurring enzymes. History Enzyme catalysis of chemical r ...


References


Further reading

*


External links

* * Point-by-point methods for citrate synthesis and hydroquinone synthesis of gold nanoparticles are availabl
here
{{DEFAULTSORT:Colloidal Gold Gold Nanoparticles by composition
Gold Gold is a chemical element with the symbol Au (from la, aurum) and atomic number 79. This makes it one of the higher atomic number elements that occur naturally. It is a bright, slightly orange-yellow, dense, soft, malleable, and ductile ...