Colloidal gold
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Colloidal gold is a
The properties of colloidal gold nanoparticles, and thus their potential applications, depend strongly upon their size and shape.[10] For example, rodlike particles have both a transverse and longitudinal absorption peak, and anisotropy of the shape affects their self-assembly.[11]
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.[12][13]
During the
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,[16] 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 (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
In 1898,
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, 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[24] 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, shape, composition and environment
As a general rule, the wavelength of light absorbed increases as a function of increasing nanoparticle size.[25] 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.[26]
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.
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.[30]
Medical research
This section needs more primary sources. (August 2017) |
Electron microscopy
Colloidal gold and various derivatives have long been among the most widely used labels for antigens in biological
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).[38]
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.[39][40] Nanoparticle-mediated drug delivery is feasible only if the drug distribution is otherwise inadequate. These cases include drug targeting of unstable (proteins, 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).[41]
Gold nanoparticles are being investigated as carriers for drugs such as Paclitaxel.[42] 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 (
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.[44]
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
Photothermal agents
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.[48][49] In 2019, the first NIR-absorbing plasmonic ultrasmall-in-nano architecture has been reported, and jointly combine: (i) a suitable photothermal conversion for hyperthermia treatments, (ii) the possibility of multiple photothermal treatments and (iii) renal excretion of the building blocks after the therapeutic action.[50]
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.
Detection of toxic gas
Researchers have developed simple inexpensive methods for on-site detection of hydrogen sulfide H
2S present in air based on the antiaggregation of gold nanoparticles (AuNPs). Dissolving H
2S into a weak alkaline 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 H
2S.[53]
Gold nanoparticle based biosensor
Gold nanoparticles are incorporated into biosensors to enhance its stability, sensitivity, and selectivity.[54] 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.[55][56] Main types of gold nanoparticle based biosensors are optical and electrochemical biosensor.
Optical biosensor
Gold nanoparticles improve the sensitivity of optical sensors in response to the change in the local refractive index. The angle of the incidence light for surface plasmon resonance, an interaction between light waves and conducting electrons in metal, changes when other substances are bounded to the metal surface.[57][58] Because gold is very sensitive to its surroundings' dielectric constant,[59][60] binding of an analyte significantly shifts the gold nanoparticle's SPR and therefore allows for more sensitive detection. Gold nanoparticle could also amplify the SPR signal.[61] When the plasmon wave pass through the gold nanoparticle, the charge density in the wave and the electron I the gold interact and result in a higher energy response, referred to as electron coupling.[54] When the analyte and bio-receptor both bind to the gold, the apparent mass of the analyte increases and therefore amplifies the signal.[54] These properties had been used to build a DNA sensor with 1000-fold greater sensitivity than without the Au NP.[62] Humidity sensors have also been 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.[63]
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".[54] It transfers electron between the electrode and the active site of the enzyme.[64] 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.[65] 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.[54] 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.[66][67] Moreover, Au NP also catalyzes biological reactions.[68][69] Gold nanoparticle under 2 nm has shown catalytic activity to the oxidation of styrene.[70]
Immunological biosensor
Gold nanoparticles have been coated with
Thin films
Gold nanoparticles capped with organic ligands, such as alkanethiol molecules, can self-assemble into large monolayers (>cm2). 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
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.[73] The mechanics of the membranes are guided by strong interactions between ligand shells on adjacent particles.[74] Upon fracture, the films crack perpendicular to the direction of strain at a fracture stress of 11 2.6 MPa, comparable to that of cross-linked polymer films.[75] 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.[76] 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.[77]
Surface chemistry
In many different types of colloidal gold syntheses, the
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.[79] 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 and functionality. For example, ligands have been shown to enhance catalytic activity by mediating interactions between adsorbates and the active gold surfaces for specific oxygenation reactions.[80] Ligand exchange can also be used to promote phase transfer of the colloidal particles.[78] 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.[81][82] 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.[83]
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.[84] 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 followed by washing. Alternatively, the ligands can be electrochemically etched off.[85]
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.[78] 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 form “staple” motifs that have significant Thiyl-Au(0) character.[86][87] 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.[88]
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,[89] 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 and in vivo. 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.[90] 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.[90] In vitro experiments are more popular than in vivo experiments because in vitro experiments are more simplistic to perform than in vivo experiments.[90]
Toxicity and hazards in synthesis
While AuNPs themselves appear to have low or negligible toxicity,[citation needed] 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, a harsh reagent, is used to reduce the gold ions to gold metal.[91] The gold ions usually come from chloroauric acid, a potent acid.[92] 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
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 (
Biosafety 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.[105][106]
Synthesis
Generally, gold nanoparticles are produced in a liquid ("liquid chemical methods") by
4]). 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.[17]
Turkevich method
This simple method was pioneered by J. Turkevich et al. in 1951
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.[112] Citrate ions or tannic acid function both as a reducing agent and a capping agent.[113][114] Less sodium citrate results in larger particles.
Brust-Schiffrin method
This method was discovered by Brust and Schiffrin in the early 1990s,
Here, the gold nanoparticles will be around 5–6 nm.
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
Perrault method
This approach, discovered by Perrault and Chan in 2009,[121] 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,[109][110] 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,[122] 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.[123] Gold nanoparticles are usually synthesized at high temperatures in organic solvents or using toxic reagents. The bacteria produce them in much milder conditions.
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.[124]
Sonolysis
Another method for the experimental generation of gold particles is by
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.[127] 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.[128] 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.[129]
See also
- Colloidal silver
- Fiveling, also called decahedral nanoparticles
- Gold nanorods
- Gold nanoparticles in chemotherapy
- Nanozymes
- Colloidal gold protein assay
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Further reading
- Boisselier E, Astruc D (June 2009). "Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity". Chemical Society Reviews. 38 (6): 1759–82. PMID 19587967.
External links
- Moriarty, Philip. "Au – Gold Nanoparticle". Sixty Symbols. Brady Haran for the University of Nottingham.
- Point-by-point methods for citrate synthesis and hydroquinone synthesis of gold nanoparticles are available here.