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 reactions occur with high selectivity and rate. The substrate is activated in a small part of the enzyme's macromolecule called the active site. There, the binding of a substrate close to functional groups in the enzyme causes catalysis by so-called proximity effects. It is possible to create similar catalysts from small molecules by combining substrate-binding with catalytic functional groups. Classically, artificial enzymes bind substrates using receptors such as cyclodextrin, crown ethers, and calixarene.
Artificial enzymes have been designed from scratch via a computational strategy using Rosetta. A December 2014 publication reported active enzymes made from molecules that do not occur in nature. In 2016, a book chapter entitled "Artificial Enzymes: The Next Wave" was published.
Nanozymes
Nanozymes are nanomaterials with enzyme-like characteristics. They have been explored for applications such as biosensing, bioimaging, tumor diagnosis and therapy, and anti-biofouling.
The term "nanozyme" was coined in 2004 by Flavio Manea, Florence Bodar Houillon, Lucia Pasquato, and Paolo Scrimin. A 2005 review article
attributed this term to "analogy with the activity of catalytic
polymers (synzymes)", based on the "outstanding catalytic efficiency of
some of the functional nanoparticles synthesized". In 2006, nanoceria
(CeO2nanoparticles) was reported to prevent retinal degeneration induced by intracellular peroxides (toxic reactive oxygen intermediates) in rat. This was seen as indicating a possible route to a treatment for certain causes of blindness. In 2007 intrinsic peroxidase-like activity of ferromagnetic nanoparticles was reported by Yan Xiyun
and coworkers as suggesting a wide range of applications in, for
example, medicine and environmental chemistry, and the authors designed
an immunoassay based on this property.
Hui Wei and Erkang Wang then (2008) used this property of easily
prepared magnetic nanoparticles to demonstrate analytical applications
to bioactive molecules, describing a colorimetric assay for hydrogen peroxide (H 2O 2) and a sensitive and selective platform for glucose detection.
2010s
As of 2016, many review articles have appeared.
A book-length treatment appeared in 2015, described as providing "a
broad portrait of nanozymes in the context of artificial enzyme
research", and a 2016 Chinese book on enzyme engineering included a chapter on nanozymes.
Colorimetric applications of peroxidase mimesis in different
preparations were reported in 2010 and 2011, detecting, respectively,
glucose (via carboxyl-modified graphene oxide) and single-nucleotide polymorphisms (in a label-free method relying on hemin−graphene hybrid nanosheets),
with advantages in both cost and convenience. A use of colour to
visualise tumour tissues was reported in 2012, using the peroxidase
mimesis of magnetic nanoparticles coated with a protein that recognises
cancer cells and binds to them.
Also in 2012, nanowires of vanadium pentoxide (vanadia, V2O5) were shown to suppress marine biofouling by mimicry of vanadium haloperoxidase, with anticipated ecological benefits. A study at a different centre two years later reported V2O5 showing mimicry of glutathione peroxidase in vitro in mammalian cells, suggesting future therapeutic application. The same year, a carboxylated fullerene dubbed C3 was reported to be neuroprotective in a primate model of Parkinson's disease.
In 2015, a supramolecular nanodevice was proposed for bioorthogonal
regulation of a transitional metal nanozyme, based on encapsulating the
nanozyme in a monolayer of hydrophilic gold nanoparticles, alternately
isolating it from the cytoplasm or allowing access according to a
gatekeeping receptor molecule controlled by competing guest
species; the device, aimed at imaging and therapeutic applications, is
of biomimetic size and was successful within the living cell,
controlling pro-fluorophore and prodrug activation. An easy means of producing Cu(OH) 2 supercages was reported, along with a demonstration of their intrinsic peroxidase mimicry. A scaffolded "INAzyme" ("integrated nanozyme") arrangement was described, locating hemin (a peroxidase mimic) with glucose oxidase
(GOx) in sub-micron proximity, providing a fast and efficient enzyme
cascade reported as monitoring cerebral brain-cell glucose dynamically in vivo.
A method of ionising hydrophobe-stabilised colloid nanoparticles was
described, with confirmation of their enzyme mimicry in aqueous
dispersion. De novo designedmetallopeptides with self-assembling properties carry out the oxidation reaction of dimethoxyphenol.
Field trials in West Africa were announced of a magnetic nanoparticle–amplified rapid low-cost strip test for Ebola virus.H 2O 2
was reported as displacing label DNA, adsorbed to nanoceria, into
solution, where it fluoresces, providing a highly sensitive glucose
test. Oxidase-like nanoceria was used for developing self-regulated bioassays. Multi-enzyme mimicking Prussian blue was developed for therapeutics. A review on metal organic framework (MOF)-based enzyme mimics was published. Histidine was used to modulate iron oxide nanoparticles' peroxidase-mimicking activities. Gold nanoparticles' peroxidase-mimicking activities were modulated via a supramolecular strategy for cascade reactions. A molecular imprinting strategy was developed to improve the selectivity of Fe3O4 nanozymes with peroxidase-like activity. A new strategy was developed to enhance the peroxidase-mimicking activity of gold nanoparticles by using hot electrons.
Researchers designed gold nanoparticle–based integrative nanozymes with
both surface-enhanced Raman scattering and peroxidase-mimicking
activities for measuring glucose and lactate in living tissues. Cytochrome c oxidase mimicking activity of Cu2O nanoparticles was modulated by receiving electrons from cytochrome c. Fe3O4 nanoparticles were combined with glucose oxidase for tumor therapeutics. Manganese dioxide nanozymes were used as cytoprotective shells. An Mn3O4 nanozyme for Parkinson's disease (cellular model) was reported. Heparin elimination in live rats was monitored with two-dimensional MOF-based peroxidase mimics and AG73 peptide.
Glucose oxidase and iron oxide nanozymes were encapsulated within
multi-compartmental hydrogels for incompatible tandem reactions. A cascade nanozyme biosensor was developed for detection of viable Enterobacter sakazakii. An integrated nanozyme of GOx@ZIF-8(NiPd) was developed for tandem catalysis. Charge-switchable nanozymes were developed. Site-selective RNA splicing nanozyme was developed. A nanozymes special issue in Progress in Biochemistry and Biophysics was published. Mn3O4 nanozymes with the ability to scavenge reactive oxygen species were developed and showed in vivo anti-inflammatory activity. A proposal entitled "A Step into the Future – Applications of Nanoparticle Enzyme Mimics" was presented. Facet-dependent oxidase and peroxidase-like activities of palladium nanoparticles were reported. Au@Pt multibranched nanostructures as bifunctional nanozymes were developed. Ferritin-coated carbon nanozymes were developed for tumor catalytic therapy. CuO nanozymes were developed to kill bacteria in a light-controlled manner. Enzymatic activity of oxygenated CNT was studied. Nanozymes were used to catalyze the oxidation of L-tyrosine and L-phenylalanine to dopachrome. Nanozymes were presented as an emerging alternative to natural enzyme for biosensing and immunoassays. A standardized assay was proposed for peroxidase-like nanozymes. Semiconductor quantum dots were utilized as nucleases for site-selective photoinduced cleavage of DNA. Two-dimensional MOF nanozyme-based sensor arrays were constructed for detecting phosphates and probing their enzymatic hydrolysis. Nitrogen-doped carbon nanomaterials as specific peroxidase mimics were reported. Nanozyme sensor arrays were developed to detect analytes from small molecules to proteins and cells. A copper oxide nanozyme for Parkinson's disease was reported. Exosome-like nanozyme vesicles for tumor imaging were developed. A comprehensive review on nanozymes was published by Chemical Society Reviews. A progress report on nanozymes was published. eg occupancy as an effective descriptor was developed for the catalytic activity of perovskite oxide–based peroxidase mimics. A Chemical Reviews paper on nanozymes was published. A single-atom strategy was used to develop nanozymes. A nanozyme for metal-free bioinspired cascade photocatalysis was reported. Chemical Society Reviews published a tutorial review on nanozymes. Cascade nanozyme reactions to fix CO2 were reported. Peroxidase-like gold nanoclusters were used to monitor renal clearance. A copper–carbon hybrid nanozyme was developed for antibacterial therapy. A ferritin nanozyme was developed to treat cerebral malaria. Accounts of Chemical Research reviewed nanozymes. A new strategy called strain effect was developed to modulate metal nanozyme activity. Prussian blue nanozymes were used to detect hydrogen sulfide in the brains of living rats. Photolyase-like CeO2 was reported. An editorial on nanozymes titled "Can Nanozymes Have an Impact on Sensing?" was published.
2020s
A single-atom nanozyme was developed for sepsis management. Self-assembled single-atom nanozyme was developed for photodynamic therapy of tumors. An ultrasound-switchable nanozyme against multidrug-resistant bacterial infection was reported. A nanozyme-based H2O2 homeostasis disruptor for chemodynamic tumor therapy was reported. An iridium oxide nanozyme for cascade reaction was developed for tumor therapy. A book entitled Nanozymology was published. A free radical–scavenging nanosponge was engineered for ischemic stroke. A minireview was published on gold-conjugate-based nanozymes. SnSe nanosheets as dehydrogenase mimics were developed. A carbon dot–based topoisomerase I mimic was reported to cleave DNA. Nanozyme sensor arrays were developed to detect pesticides. Bioorthogonal nanozymes were used to treat bacterial biofilms. A rhodium nanozyme was developed for treat colon disease. A Fe-N-C nanozyme was developed to study drug–drug interactions. A polymeric nanozyme was developed for second near-infrared photothermal cancer ferrotherapy. A Cu5.4O nanozyme was reported for anti-inflammation therapy. A CeO2@ZIF-8 nanozyme was developed to treat reperfusion-induced injury in ischemic stroke. Peroxidase-like activity of Fe3O4 was explored to study the electrocatalytic kinetics at the single-molecule/single-particle level. A Cu-TA nanozyme was fabricated to scavenge reactive oxygen species from cigarette smoke. A metalloenzyme-like copper nanocluster was reported to have anticancer and imaging activities simultaneously. An integrated nanozyme was developed for anti-inflammation therapy. Enhanced enzyme-like catalytic activity was reported under non-equilibrium conditions for gold nanozymes. A density functional theory method was proposed to predict the activities of peroxidase-like nanozymes. A hydrolytic nanozyme was developed to construct an immunosensor. An orally administered nanozyme was developed for inflammatory bowel disease therapy.
A ligand-dependent activity engineering strategy was reported to
develop a glutathione peroxidase–mimicking MIL-47(V) metal–organic
framework nanozyme for therapy. A single-site nanozyme was developed for tumor therapy. A SOD-like nanozyme was developed to regulate the mitochondria and neural cell function. A Pd12 coordination cage as a photoregulated oxidase-like nanozyme was developed. An NADPH oxidase-like nanozyme was developed. A catalase-like nanozyme was developed for tumor therapy. A defect-rich adhesive molybdenum disulfide/reduced graphene oxide nanozyme was developed for anti-bacterial activity. A MOF@COF nanozyme was developed for anti-bacterial activity. Plasmonic nanozymes were reported. Tumor microenvironment–responsive nanozyme was developed for tumor therapy. A protein-engineering-inspired method was developed to design highly active nanozymes. An editorial on nanozymes definition was published. A nanozyme therapy for hyperuricemia and ischemic stroke was developed. Chemistry World published a perspective on artificial enzymes and nanozymes. A review on single-atom catalysts, including single-atom nanozymes, was published. Peroxidase-like mixed-FeCo-oxide-based surface-textured nanostructures (MTex) were used for biofilm eradication. A nanozyme with better kinetics than natural peroxidase was developed. A self-protecting nanozyme was developed for Alzheimer's disease. CuSe nanozymes was developed to treat Parkinson's disease. A nanocluster-based nanozyme was developed. Glucose oxidase–like gold nanoparticles combined with cyclodextran were used for chiral catalysis. An artificial binuclear copper monooxygenase in a MOF was developed. A review on highly efficient design of nanozymes was published. Ni–Pt peroxidase mimics were developed for bioanalysis. A POM-based nanozyme was reported to protect cells from reactive oxygen species. A gating strategy was used to prepare selective nanozymes. A manganese single-atom nanozyme was developed for tumor therapy. A pH-responsive oxidase-like graphitic nanozyme was developed for selective killing of Helicobacter pylori. An engineered FeN3P-centred single-atom nanozyme was developed. Peroxidase- and catalase-like activities of gold nanozymes were modulated. Graphdiyne–cerium oxide nanozymes were developed for radiotherapy of esophageal cancer. Defect engineering was used to develop nanozyme for tumor therapy. A book entitled Nanozymes for Environmental Engineering was published. A palladium single-atom nanozyme was developed for tumor therapy. A horseradish peroxidase–like nanozyme was developed for tumor therapy. The mechanism of a GOx-like nanozyme was reported. A review on nanozymes was published. A mechanism study on nanonuclease-like nanozyme was reported. A perspective on nanozyme definition was published. Aptananozymes were developed. Ceria nanozyme loaded microneedles helped hair regrowth. A catalase-like platinum nanozyme was used for small extracellular vesicles analysis. A book on Nanozymes: Advances and Applications was published by CRC Press. A review on nanozyme catalytic turnover was published. A nanozyme was developed for ratiometric molecular imaging. A Fe3O4/Ag/Bi2MoO6 photoactivatable nanozyme was developed for cancer therapy. Co/C as an NADH oxidase mimic was reported. An iron oxide nanozyme was used to target biofilms causing tooth decay. A new strategy for high-performance nanozymes was developed. A high-throughput computational screening strategy was developed to discover SOD-like nanozymes. A review paper entitled "Nanozyme-Enabled Analytical Chemistry" was published in Analytical Chemistry. A nanozyme-based therapy for gout was reported. A data-informed strategy for discovery of nanozymes was reported. Prussian blue nanozyme was used to alleviates neurodegeneration. A dual element single-atom nanozyme was developed. A valence-engineered method was developed to design antioxidant banozyme for biomedical applications. Combined with small interfering RNA, ceria nanozyme was used for synergistic treatment of neurodegenerative diseases. A universal assay for catalase-like nanozymes was reported. A nanozyme catalyzed CRISPR assay was developed. A nanozyme-based tumor-specific photo-enhanced catalytic therapy was developed. Single-atom nanozymes for brain trauma therapy were reported. An edge engineering strategy was developed to fabriacte single atom nanozymes. A single atom nanozyme was developed to modulate tumor microenvironment for therapy. A new mechanism for peroxidase-like Fe3O4 was proposed. A plant virus cleaving nanozyme was reported. Nanozymes is selected as one of the IUPAC Top Ten Emerging Technologies in Chemistry 2022. A book entitled "Nanozymes: Design, Synthesis, and Applications" was published by ACS. Nanozymes were used to remove and degrade microplastics. A cold-adapted nanozyme was reported. A MOF-818 nanozyme with antioxidase-mimicking activities was used to treat diabetic chronic wounds. Cu single-atom nanozymes were developed for catalytic tumor-specific therapy. Machine learning was employed to search for nanozymes. Enzyme-like meso-bacroporous carbon sphere was developed. A combination of DNAzyme and nanozyme was reported. A peroxidase-like photoexcited Ru single-atom nanozyme was reported. A probiotic nanozyme hydrogel for Candida vaginitis therapy was developed. A method to determine the maximum velocity of a peroxidase-like nanozyme was proposed. Antisenescence nanozymes for atherosclerosis therapy were reported. A book entitled 'Biomedical Nanozymes: From Diagnostics to Therapeutics' was published by Springer. 2023 Dalton Division Horizon Prize was awarded to High-Performance Nanozyme Designer. Nanozyme-cosmetic contact lenses were developed. Biogenic ferritins act as natural nanozymes were reported. An integrated computational and experimental framework for inverse screening of nanozymes was developed. A diatomic iron nanozyme was reported. Mechanism of carbon dot-based SOD-like nanozyme was studied. A hybrid ceria nanozyme was developed for arthritis therapy. A chiral nanozyme was reported for Parkinson's disease. A dimensionality-engineered single-atom nanozyme was reported. A liposome-base nanozyme was developed to treat infected diabetic wounds. A single-site iron nanozyme was developed for alcohol detoxification. A Pt nanozyme was developed to treat gouty arthritis. Two nature reviews on nanozymes were published, focusing on nanohealthcare and in vivo applications. Combination of nanozyme and probiotics for IBD therapy. An artificial metabzyme for tumour-cell-specific metabolic therapy was reported. Inhalable nanozyme for viral pneumonia therapy.
A strategy to modulate the microenvironmental pHs of nanozymes was
developed and the modulated nanozymes were used for analysis including
chiral analysis.
Certain nanozymes have the potential for treating ischemic stroke and
traumatic brain injury due to their ability to mitigate the harmful
effects of excessive free radical production, oxidative brain damage,
inflammation, and blood-brain barrier disruption.
Nanomaterials research takes a materials science-based approach to nanotechnology, leveraging advances in materials metrology and synthesis which have been developed in support of microfabrication
research. Materials with structure at the nanoscale often have unique
optical, electronic, thermo-physical or mechanical properties.
Nanomaterials are slowly becoming commercialized and beginning to emerge as commodities.
Definition
In ISO/TS 80004, nanomaterial
is defined as the "material with any external dimension in the
nanoscale or having internal structure or surface structure in the
nanoscale", with nanoscale defined as the "length range approximately from 1 nm to 100 nm". This includes both nano-objects, which are discrete pieces of material, and nanostructured materials, which have internal or surface structure on the nanoscale; a nanomaterial may be a member of both these categories.
On 18 October 2011, the European Commission adopted the following definition of a nanomaterial:
A
natural, incidental or manufactured material containing particles, in
an unbound state or as an aggregate or as an agglomerate and for 50% or
more of the particles in the number size distribution, one or more
external dimensions is in the size range 1 nm – 100 nm. In specific
cases and where warranted by concerns for the environment, health,
safety or competitiveness the number size distribution threshold of 50%
may be replaced by a threshold between 1% to 50%.
Sources
Engineered
Engineered nanomaterials have been deliberately engineered and manufactured by humans to have certain required properties.
Legacy nanomaterials are those that were in commercial production
prior to the development of nanotechnology as incremental advancements
over other colloidal or particulate materials.They include carbon black and titanium dioxide nanoparticles.
Incidental
Nanomaterials
may be unintentionally produced as a byproduct of mechanical or
industrial processes through combustion and vaporization. Sources of
incidental nanoparticles include vehicle engine exhausts, smelting,
welding fumes, combustion processes from domestic solid fuel heating and
cooking. For instance, the class of nanomaterials called fullerenes are generated by burning gas, biomass, and candle. It can also be a byproduct of wear and corrosion products. Incidental atmospheric nanoparticles are often referred to as ultrafine particles, which are unintentionally produced during an intentional operation, and could contribute to air pollution.
Natural
Biological systems often feature natural, functional nanomaterials. The structure of foraminifera (mainly chalk) and viruses (protein, capsid), the wax crystals covering a lotus or nasturtium leaf, spider and spider-mite silk, the blue hue of tarantulas, the "spatulae" on the bottom of gecko feet, some butterfly wing scales, natural colloids (milk, blood), horny materials (skin, claws, beaks, feathers, horns, hair), paper, cotton, nacre, corals, and even our own bone matrix are all natural organic nanomaterials.
Natural inorganic nanomaterials occur through crystal growth in the diverse chemical conditions of the Earth's crust. For example, clays display complex nanostructures due to anisotropy of their underlying crystal structure, and volcanic activity can give rise to opals, which are an instance of a naturally occurring photonic crystals due to their nanoscale structure. Fires represent particularly complex reactions and can produce pigments, cement, fumed silica etc.
Natural sources of nanoparticles include combustion products
forest fires, volcanic ash, ocean spray, and the radioactive decay of radon gas. Natural nanomaterials can also be formed through weathering processes of metal- or anion-containing rocks, as well as at acid mine drainage sites.
"Lotus effect", hydrophobic effect with self-cleaning ability
Close-up of the underside of a gecko's foot as it walks on a glass wall (spatula: 200 × 10–15 nm)
SEM micrograph of a butterfly wing scale (× 5000)
Peacock feather (detail)
Brazilian Crystal Opal. The play of color is
caused by the interference and diffraction of light between silica
spheres (150–300 nm in diameter).
Blue hue of a species of tarantula (450 nm ± 20 nm)
Types
Nano-materials are often categorized as to how many of their dimensions fall in the nanoscale. A nanoparticle
is defined a nano-object with all three external dimensions in the
nanoscale, whose longest and the shortest axes do not differ
significantly. A nanofiber has two external dimensions in the nanoscale, with nanotubes being hollow nanofibers and nanorods being solid nanofibers. A nanoplate/nanosheet has one external dimension in the nanoscale, and if the two larger dimensions are significantly different it is called a nanoribbon.
For nanofibers and nanoplates, the other dimensions may or may not be
in the nanoscale, but must be significantly larger. In all of these
cases, a significant difference is noted to typically be at least a
factor of 3.
Nanostructured materials are often categorized by what phases of matter they contain. A nanocomposite
is a solid containing at least one physically or chemically distinct
region or collection of regions, having at least one dimension in the
nanoscale. A nanofoam has a liquid or solid matrix, filled with a gaseous phase, where one of the two phases has dimensions on the nanoscale. A nanoporous material is a solid material containing nanopores, voids in the form of open or closed pores of sub-micron lengthscales. A nanocrystalline material has a significant fraction of crystal grains in the nanoscale.
The term nanoporous materials contain subsets of microporous
and mesoporous materials. Microporous materials are porous materials
with a mean pore size smaller than 2 nm, while mesoporous materials are
those with pores sizes in the region 2–50 nm.
Microporous materials exhibit pore sizes with comparable length-scale
to small molecules. For this reason such materials may serve valuable
applications including separation membranes. Mesoporous materials are
interesting towards applications that require high specific surface
areas, while enabling penetration for molecules that may be too large to
enter the pores of a microporous material. In some sources, nanoporous
materials and nanofoam are sometimes considered nanostructures but not
nanomaterials because only the voids and not the materials themselves
are nanoscale. Although the ISO definition only considers round nano-objects to be nanoparticles, other sources use the term nanoparticle for all shapes.
The fullerenes are a class of allotropes of carbon which conceptually are graphene sheets rolled into tubes or spheres. These include the carbon nanotubes (or silicon nanotubes) which are of interest both because of their mechanical strength and also because of their electrical properties.
For the past decade, the chemical and physical properties of
fullerenes have been a hot topic in the field of research and
development, and are likely to continue to be for a long time. In
April 2003, fullerenes were under study for potential medicinal use: binding specific antibiotics to the structure of resistant bacteria and even target certain types of cancer cells such as melanoma. The October 2005 issue of Chemistry and Biology contains an article describing the use of fullerenes as light-activated antimicrobial agents. In the field of nanotechnology, heat resistance and superconductivity are among the
properties attracting intense research.
A common method used to produce fullerenes is to send a large
current between two nearby graphite electrodes in an inert atmosphere.
The resulting carbonplasma arc between the electrodes cools into sooty residue from which many fullerenes can be isolated.
There are many calculations that have been done using ab-initio Quantum Methods applied to fullerenes. By DFT and TDDFT methods one can obtain IR, Raman, and UV spectra. Results of such calculations can be compared with experimental results.
Metal-based nanoparticles
Inorganic nanomaterials, (e.g. quantum dots, nanowires, and nanorods) because of their interesting optical and electrical properties, could be used in optoelectronics.
Furthermore, the optical and electronic properties of nanomaterials
which depend on their size and shape can be tuned via synthetic
techniques. There are the possibilities to use those materials in
organic material based optoelectronic devices such as organic solar cells, OLEDs etc. The operating principles of such devices are governed by photoinduced processes like electron transfer
and energy transfer. The performance of the devices depends on the
efficiency of the photoinduced process responsible for their
functioning. Therefore, better understanding of those photoinduced
processes in organic/inorganic nanomaterial composite systems is
necessary in order to use them in optoelectronic devices.
Nanoparticles or nanocrystals made of metals, semiconductors, or
oxides are of particular interest for their mechanical, electrical,
magnetic, optical, chemical and other properties.Nanoparticles have been used as quantum dots and as chemical catalysts such as nanomaterial-based catalysts. Recently, a range of nanoparticles are extensively investigated for biomedical applications including tissue engineering, drug delivery, biosensor.
Nanoparticles are of great scientific interest as they are effectively a bridge between bulk materials and atomic or molecular
structures. A bulk material should have constant physical properties
regardless of its size, but at the nano-scale this is often not the
case. Size-dependent properties are observed such as quantum confinement in semiconductor particles, surface plasmon resonance in some metal particles, and superparamagnetism in magnetic materials.
Nanoparticles exhibit a number of special properties relative to bulk material. For example, the bending of bulk copper (wire, ribbon, etc.) occurs with movement of copper atoms/clusters at about the 50 nm scale. Copper nanoparticles smaller than 50 nm are considered super hard materials that do not exhibit the same malleability and ductility
as bulk copper. The change in properties is not always desirable.
Ferroelectric materials smaller than 10 nm can switch their polarization
direction using room temperature thermal energy, thus making them
useless for memory storage. Suspensions of nanoparticles are possible because the interaction of the particle surface with the solvent is strong enough to overcome differences in density,
which usually result in a material either sinking or floating in a
liquid. Nanoparticles often have unexpected visual properties because
they are small enough to confine their electrons and produce quantum
effects. For example, gold nanoparticles appear deep red to black in solution.
The often very high surface area to volume ratio of nanoparticles provides a tremendous driving force for diffusion, especially at elevated temperatures. Sintering
is possible at lower temperatures and over shorter durations than for
larger particles. This theoretically does not affect the density of the
final product, though flow difficulties and the tendency of
nanoparticles to agglomerate do complicate matters. The surface effects
of nanoparticles also reduces the incipient melting temperature.
One-dimensional nanostructures
The
smallest possible crystalline wires with cross-section as small as a
single atom can be engineered in cylindrical confinement. Carbon nanotubes,
a natural semi-1D nanostructure, can be used as a template for
synthesis. Confinement provides mechanical stabilization and prevents
linear atomic chains from disintegration; other structures of 1D nanowires are predicted to be mechanically stable even upon isolation from the templates.
Two-dimensional nanostructures
2D materials are crystalline materials consisting of a two-dimensional single layer of atoms. The most important representative graphene was discovered in 2004.
Thin films with nanoscale thicknesses (nanofilms)
are considered nanostructures, but are sometimes not considered
nanomaterials because they do not exist separately from the substrate.
Box-shaped graphene (BSG) nanostructure is an example of 3D nanomaterial. BSG nanostructure has appeared after mechanical cleavage of pyrolytic graphite.
This nanostructure is a multilayer system of parallel hollow
nanochannels located along the surface and having quadrangular
cross-section. The thickness of the channel walls is approximately equal
to 1 nm. The typical width of channel facets makes about 25 nm.
Nano materials are used in a variety of, manufacturing processes, products and healthcare including paints, filters, insulation and lubricant additives. In healthcare Nanozymes are nanomaterials with enzyme-like characteristics. They are an emerging type of artificial enzyme, which have been used for wide applications in such as biosensing, bioimaging, tumor diagnosis,
antibiofouling and more. High quality filters may be produced using
nanostructures, these filters are capable of removing particulate as
small as a virus as seen in a water filter created by Seldon Technologies. Nanomaterials membrane bioreactor (NMs-MBR), the next generation of conventional MBR, are recently proposed for the advanced treatment of wastewater. In the air purification field, nano technology was used to combat the spread of MERS in Saudi Arabian hospitals in 2012. Nanomaterials are being used in modern and human-safe insulation technologies; in the past they were found in Asbestos-based insulation.
As a lubricant additive, nano materials have the ability to reduce
friction in moving parts. Worn and corroded parts can also be repaired
with self-assembling anisotropic nanoparticles called TriboTEX. Nanomaterials have also been applied in a range of industries and consumer products. Mineral nanoparticles such as titanium-oxide have been used to improve UV protection in sunscreen.
In the sports industry, lighter bats to have been produced with carbon
nanotubes to improve performance. Another application is in the
military, where mobile pigment nanoparticles have been used to create
more effective camouflage. Nanomaterials can also be used in
three-way-catalyst applications, which have the advantage of controlling
the emission of nitrogen oxides (NOx), which are precursors to acid rain and smog.
In core-shell structure, nanomaterials form shell as the catalyst
support to protect the noble metals such as palladium and rhodium.
The primary function is that the supports can be used for carrying
catalysts active components, making them highly dispersed, reducing the
use of noble metals, enhancing catalysts activity, and potentially
improving the stability.
Synthesis
The
goal of any synthetic method for nanomaterials is to yield a material
that exhibits properties that are a result of their characteristic
length scale being in the nanometer range (1 – 100 nm). Accordingly, the
synthetic method should exhibit control of size in this range so that
one property or another can be attained. Often the methods are divided
into two main types, "bottom up" and "top down".
Bottom-up methods
Bottom-up
methods involve the assembly of atoms or molecules into nanostructured
arrays. In these methods the raw material sources can be in the form of
gases, liquids, or solids. The latter require some sort of disassembly
prior to their incorporation onto a nanostructure. Bottom up methods
generally fall into two categories: chaotic and controlled.
Chaotic processes involve elevating the constituent atoms or
molecules to a chaotic state and then suddenly changing the conditions
so as to make that state unstable. Through the clever manipulation of
any number of parameters, products form largely as a result of the
insuring kinetics. The collapse from the chaotic state can be difficult
or impossible to control and so ensemble statistics often govern the
resulting size distribution and average size. Accordingly, nanoparticle
formation is controlled through manipulation of the end state of the
products. Examples of chaotic processes are laser ablation, exploding wire, arc, flame pyrolysis, combustion, and precipitation synthesis techniques.
Controlled processes involve the controlled delivery of the
constituent atoms or molecules to the site(s) of nanoparticle formation
such that the nanoparticle can grow to a prescribed sizes in a
controlled manner. Generally the state of the constituent atoms or
molecules are never far from that needed for nanoparticle formation.
Accordingly, nanoparticle formation is controlled through the control of
the state of the reactants. Examples of controlled processes are
self-limiting growth solution, self-limited chemical vapor deposition, shaped pulse femtosecond laser techniques, plant and microbial approaches and molecular beam epitaxy.
Top-down methods
Top-down
methods adopt some 'force' (e. g. mechanical force, laser) to break
bulk materials into nanoparticles. A popular method involves mechanical
break apart bulk materials into nanomaterials is 'ball milling'. Besides
that, nanoparticles can also be made by laser ablation which apply
short pulse lasers (e. g. femtosecond laser) to ablate a target (solid).
Novel effects can occur in materials when structures are formed with sizes comparable to any one of many possible length scales, such as the de Broglie wavelength of electrons, or the optical wavelengths of high energy photons. In these cases quantum mechanical effects can dominate material properties. One example is quantum confinement
where the electronic properties of solids are altered with great
reductions in particle size. The optical properties of nanoparticles,
e.g. fluorescence,
also become a function of the particle diameter. This effect does not
come into play by going from macrosocopic to micrometer dimensions, but
becomes pronounced when the nanometer scale is reached.
In addition to optical and electronic properties, the novel mechanical properties of many nanomaterials is the subject of nanomechanics
research. When added to a bulk material, nanoparticles can strongly
influence the mechanical properties of the material, such as the
stiffness or elasticity. For example, traditional polymers can be reinforced by nanoparticles (such as carbon nanotubes) resulting in novel materials which can be used as lightweight replacements for metals. Such composite materials may enable a weight reduction accompanied by an increase in stability and improved functionality.
Finally, nanostructured materials with small particle size, such as zeolites and asbestos, are used as catalysts
in a wide range of critical industrial chemical reactions. The further
development of such catalysts can form the basis of more efficient,
environmentally friendly chemical processes.
The first observations and size measurements of nano-particles
were made during the first decade of the 20th century. Zsigmondy made
detailed studies of gold sols and other nanomaterials with sizes down to
10 nm and less. He published a book in 1914. He used an ultramicroscope that employs a dark field method for seeing particles with sizes much less than lightwavelength.
There are traditional techniques developed during the 20th century in interface and colloid science for characterizing nanomaterials. These are widely used for first generation passive nanomaterials specified in the next section.
These methods include several different techniques for characterizing particle size distribution.
This characterization is imperative because many materials that are
expected to be nano-sized are actually aggregated in solutions. Some of
methods are based on light scattering. Others apply ultrasound, such as ultrasound attenuation spectroscopy for testing concentrated nano-dispersions and microemulsions.
The
ongoing research has shown that mechanical properties can vary
significantly in nanomaterials compared to bulk material. Nanomaterials
have substantial mechanical properties due to the volume, surface, and
quantum effects of nanoparticles. This is observed when the
nanoparticles are added to common bulk material, the nanomaterial
refines the grain and forms intergranular and intragranular structures
which improve the grain boundaries and therefore the mechanical
properties of the materials.
Grain boundary refinements provide strengthening by increasing the
stress required to cause intergranular or transgranular fractures. A
common example where this can be observed is the addition of nano Silica
to cement, which improves the tensile strength, compressive strength,
and bending strength by the mechanisms just mentioned. The understanding
of these properties will enhance the use of nanoparticles in novel
applications in various fields such as surface engineering, tribology,
nanomanufacturing, and nanofabrication.
Techniques used:
Steinitz in 1943 used the micro-indentation technique to test the
hardness of microparticles, and now nanoindentation has been employed
to measure elastic properties of particles at about 5-micron level.
These protocols are frequently used to calculate the mechanical
characteristics of nanoparticles via atomic force microscopy (AFM)
techniques. To measure the elastic modulus; indentation data is obtained
via AFM force-displacement curves being converted to force-indentation
curves. Hooke's law
is used to determine the cantilever deformation and depth of the tip,
and in conclusion, the pressure equation can be written as:
P=k (ẟc - ẟc0)
ẟc : cantilever deformation
ẟc0 : deflection ofset
AFM allows us to obtain a high-resolution image of multiple types
of surfaces while the tip of the cantilever can be used to obtain
information about mechanical properties. Computer simulations are also
being progressively used to test theories and complement experimental
studies. The most used computer method is molecular dynamics simulation,
which uses newton's equations of motion for the atoms or molecules in
the system. Other techniques such direct probe method are used to
determine the adhesive properties of nanomaterials. Both the technique
and simulation are coupled with transmission electron microscope (TEM)
and AFM techniques to provide results.
Mechanical properties of common nanomaterials classes:
Crystalline metal nanomaterials: Dislocations are one of
the major contributors toward elastic properties within nanomaterials
similar to bulk crystalline materials. Despite the traditional view of
there being no dislocations in nanomaterials. Ramos,
experimental work has shown that the hardness of gold nanoparticles is
much higher than their bulk counterparts, as there are stacking faults
and dislocations forming that activate multiple strengthening mechanisms
in the material. Through these experiments, more research has shown
that via nanoindentation techniques,
material strength; compressive stress, increases under compression with
decreasing particle size, because of nucleating dislocations. These
dislocations have been observed using TEM techniques, coupled with
nanoindentation. Silicon nanoparticles strength and hardness are four
times more than the value of the bulk material.
The resistance to pressure applied can be attributed to the line
defects inside the particles as well as a dislocation that provides
strengthening of the mechanical properties of the nanomaterial.
Furthermore, the addition of nanoparticles strengthens a matrix because
the pinning of particles inhibits grain growth. This refines the grain,
and hence improves the mechanical properties.
However, not all additions of nanomaterials lead to an increase in
properties for example nano-Cu. But this is attributed to the inherent
properties of the material being weaker than the matrix.
Nonmetallic nanoparticles and nanomaterials:
Size-dependent behavior of mechanical properties is still not clear in
the case of polymer nanomaterials however, in one research by Lahouij
they found that the compressive moduli of polystyrene nanoparticles were
found to be less than that of the bulk counterparts. This can be
associated with the functional groups being hydrated.
Furthermore, nonmetallic nanomaterials can lead to agglomerates forming
inside the matrix they are being added to and hence decrease the
mechanical properties by leading to fracture under even low mechanical
loads, such as the addition of CNTs. The agglomerates will act as slip
planes as well as planes in which cracks can easily propagate (9).
However, most organic nanomaterials are flexible and these and the
mechanical properties such as hardness etc. are not dominant.
Nanowires and nanotubes: The elastic moduli of some
nanowires namely lead and silver, decrease with increasing diameter.
This has been associated with surface stress, oxidation layer, and
surface roughness.
However, the elastic behavior of ZnO nanowires does not get affected by
surface effects but their fracture properties do. So, it is generally
dependent on material behavior and their bonding as well.
The reason why mechanical properties of nanomaterials are still a
hot topic for research is that measuring the mechanical properties of
individual nanoparticles is a complicated method, involving multiple
control factors. Nonetheless, Atomic force microscopy has been widely
used to measure the mechanical properties of nanomaterials.
Adhesion and friction of nanoparticles
When talking about the application of a material adhesion and
friction play a critical role in determining the outcome of the
application. Therefore, it is critical to see how these properties also
get affected by the size of a material. Again, AFM is a technique most
used to measure these properties and to determine the adhesive strength
of nanoparticles to any solid surface, along with the colloidal probe
technique and other chemical properties.
Furthermore, the forces playing a role in providing these adhesive
properties to nanomaterials are either the electrostatic forces, VdW,
capillary forces, solvation forces, structure force, etc. It has been
found that the addition of nanomaterials in bulk materials substantially
increases their adhesive capabilities by increasing their strength
through various bonding mechanisms. Nanomaterials dimension approaches zero, which means that the fraction of the particle's surface to overall atoms increases.
Along with surface effects, the movement of nanoparticles also
plays a role in dictating their mechanical properties such as shearing
capabilities. The movement of particles can be observed under TEM. For
example, the movement behavior of MoS2
nanoparticles dynamic contact was directly observed in situ which led
to the conclusion that fullerenes can shear via rolling or sliding.
However, observing these properties is again a very complicated process
due to multiple contributing factors.
Applications specific to Mechanical Properties:
Lubrication
Nano-manufacturing
Coatings
Uniformity
The
chemical processing and synthesis of high performance technological
components for the private, industrial and military sectors requires the
use of high purity ceramics, polymera, glass-ceramics, and composite materials. In condensed bodies formed from fine powders, the irregular sizes and shapes of nanoparticles
in a typical powder often lead to non-uniform packing morphologies that
result in packing density variations in the powder compact.
Uncontrolled agglomeration of powders due to attractivevan der Waals forces
can also give rise to in microstructural inhomogeneities. Differential
stresses that develop as a result of non-uniform drying shrinkage are
directly related to the rate at which the solvent can be removed, and thus highly dependent upon the distribution of porosity. Such stresses have been associated with a plastic-to-brittle transition in consolidated bodies, and can yield to crack propagation in the unfired body if not relieved.
In addition, any fluctuations in packing density in the compact as it is prepared for the kiln are often amplified during the sintering process, yielding inhomogeneous densification. Some pores and other structural defects
associated with density variations have been shown to play a
detrimental role in the sintering process by growing and thus limiting
end-point densities. Differential stresses arising from inhomogeneous
densification have also been shown to result in the propagation of
internal cracks, thus becoming the strength-controlling flaws.
It would therefore appear desirable to process a material in such
a way that it is physically uniform with regard to the distribution of
components and porosity, rather than using particle size distributions
which will maximize the green density. The containment of a uniformly
dispersed assembly of strongly interacting particles in suspension
requires total control over particle-particle interactions. A number of
dispersants such as ammonium citrate (aqueous) and imidazoline or oleyl alcohol (nonaqueous) are promising solutions as possible additives for enhanced dispersion and deagglomeration. Monodisperse nanoparticles and colloids provide this potential.
Monodisperse powders of colloidal silica, for example, may therefore be stabilized sufficiently to ensure a high degree of order in the colloidal crystal or polycrystalline
colloidal solid which results from aggregation. The degree of order
appears to be limited by the time and space allowed for longer-range
correlations to be established. Such defective polycrystalline colloidal
structures would appear to be the basic elements of sub-micrometer
colloidal materials science, and, therefore, provide the first step in
developing a more rigorous understanding of the mechanisms involved in
microstructural evolution in high performance materials and components.
Nanomaterials in articles, patents, and products
The
quantitative analysis of nanomaterials showed that nanoparticles,
nanotubes, nanocrystalline materials, nanocomposites, and graphene have
been mentioned in 400,000, 181,000, 144,000, 140,000, and 119,000
ISI-indexed articles, respectively, by September 2018. As far as patents
are concerned, nanoparticles, nanotubes, nanocomposites, graphene, and
nanowires have been played a role in 45,600, 32,100, 12,700, 12,500, and
11,800 patents, respectively. Monitoring approximately 7,000 commercial
nano-based products available on global markets revealed that the
properties of around 2,330 products have been enabled or enhanced aided
by nanoparticles. Liposomes, nanofibers, nanocolloids, and aerogels were
also of the most common nanomaterials in consumer products.
This section needs to be updated. The reason given is:
Quote:
“... nanotechnology products classified (2019–2023) according with
industrial areas: electronics, medicine, construction,
cosmetics,etc...”. Please help update this article to reflect recent events or newly available information.(March 2024)
World Health Organization guidelines
The
World Health Organization (WHO) published a guideline on protecting
workers from potential risk of manufactured nanomaterials at the end of
2017.
WHO used a precautionary approach as one of its guiding principles.
This means that exposure has to be reduced, despite uncertainty about
the adverse health effects, when there are reasonable indications to do
so. This is highlighted by recent scientific studies that demonstrate a
capability of nanoparticles to cross cell barriers and interact with cellular structures.
In addition, the hierarchy of controls was an important guiding
principle. This means that when there is a choice between control
measures, those measures that are closer to the root of the problem
should always be preferred over measures that put a greater burden on
workers, such as the use of personal protective equipment (PPE). WHO
commissioned systematic reviews for all important issues to assess the
current state of the science and to inform the recommendations according
to the process set out in the WHO Handbook for guideline development.
The recommendations were rated as "strong" or "conditional" depending on
the quality of the scientific evidence, values and preferences, and
costs related to the recommendation.
The WHO guidelines contain the following recommendations for safe handling of manufactured nanomaterials (MNMs)
A. Assess health hazards of MNMs
WHO recommends assigning hazard classes to all MNMs according to
the Globally Harmonized System (GHS) of Classification and Labelling of
Chemicals for use in safety data sheets. For a limited number of MNMs
this information is made available in the guidelines (strong
recommendation, moderate-quality evidence).
WHO recommends updating safety data sheets with MNM-specific hazard
information or indicating which toxicological end-points did not have
adequate testing available (strong recommendation, moderate-quality
evidence).
For the respirable fibres and granular biopersistent particles'
groups, the GDG suggests using the available classification of MNMs for
provisional classification of nanomaterials of the same group
(conditional recommendation, low-quality evidence).
B. Assess exposure to MNMs
WHO suggests assessing workers' exposure in workplaces with
methods similar to those used for the proposed specific occupational
exposure limit (OEL) value of the MNM (conditional recommendation,
low-quality evidence).
Because there are no specific regulatory OEL values for MNMs in
workplaces, WHO suggests assessing whether workplace exposure exceeds a
proposed OEL value for the MNM. A list of proposed OEL values is
provided in an annex of the guidelines. The chosen OEL should be at
least as protective as a legally mandated OEL for the bulk form of the
material (conditional recommendation, low-quality evidence).
If specific OELs for MNMs are not available in workplaces, WHO
suggests a step-wise approach for inhalation exposure with, first an
assessment of the potential for exposure; second, conducting basic
exposure assessment and third, conducting a comprehensive exposure
assessment such as those proposed by the Organisation for Economic
Cooperation and Development (OECD) or Comité Européen de Normalisation
(the European Committee for Standardization, CEN) (conditional
recommendation, moderate quality evidence).
For dermal exposure assessment, WHO found that there was
insufficient evidence to recommend one method of dermal exposure
assessment over another.
C. Control exposure to MNMs
Based on a precautionary approach, WHO recommends focusing
control of exposure on preventing inhalation exposure with the aim of
reducing it as much as possible (strong recommendation, moderate-quality
evidence).
WHO recommends reduction of exposures to a range of MNMs that have
been consistently measured in workplaces especially during cleaning and
maintenance, collecting material from reaction vessels and feeding MNMs
into the production process. In the absence of toxicological
information, WHO recommends implementing the highest level of controls
to prevent workers from any exposure. When more information is
available, WHO recommends taking a more tailored approach (strong
recommendation, moderate-quality evidence).
WHO recommends taking control measures based on the principle of
hierarchy of controls, meaning that the first control measure should be
to eliminate the source of exposure before implementing control measures
that are more dependent on worker involvement, with PPE being used only
as a last resort. According to this principle, engineering controls
should be used when there is a high level of inhalation exposure or when
there is no, or very little, toxicological information available. In
the absence of appropriate engineering controls PPE should be used,
especially respiratory protection, as part of a respiratory protection
programme that includes fit-testing (strong recommendation,
moderate-quality evidence).
WHO suggests preventing dermal exposure by occupational hygiene
measures such as surface cleaning, and the use of appropriate gloves
(conditional recommendation, low quality evidence).
When assessment and measurement by a workplace safety expert is not
available, WHO suggests using control banding for nanomaterials to
select exposure control measures in the workplace. Owing to a lack of
studies, WHO cannot recommend one method of control banding over another
(conditional recommendation, very low-quality evidence).
For health surveillance WHO could not make a recommendation for
targeted MNM-specific health surveillance programmes over existing
health surveillance programmes that are already in use owing to the lack
of evidence. WHO considers training of workers and worker involvement
in health and safety issues to be best practice but could not recommend
one form of training of workers over another, or one form of worker
involvement over another, owing to the lack of studies available. It is
expected that there will be considerable progress in validated
measurement methods and risk assessment and WHO expects to update these
guidelines in five years' time, in 2022.
Other guidance
Because
nanotechnology is a recent development, the health and safety effects
of exposures to nanomaterials, and what levels of exposure may be
acceptable, are subjects of ongoing research. Of the possible hazards, inhalation exposure appears to present the most concern. Animal studies indicate that carbon nanotubes and carbon nanofibers can cause pulmonary effects including inflammation, granulomas, and pulmonary fibrosis, which were of similar or greater potency when compared with other known fibrogenic materials such as silica, asbestos, and ultrafine carbon black.
Acute inhalation exposure of healthy animals to biodegradable inorganic
nanomaterials have not demonstrated significant toxicity effects.
Although the extent to which animal data may predict clinically
significant lung effects in workers is not known, the toxicity seen in
the short-term animal studies indicate a need for protective action for
workers exposed to these nanomaterials, although no reports of actual
adverse health effects in workers using or producing these nanomaterials
were known as of 2013. Additional concerns include skin contact and ingestion exposure, and dust explosion hazards.
Elimination and substitution are the most desirable approaches to hazard control. While the nanomaterials themselves often cannot be eliminated or substituted with conventional materials, it may be possible to choose properties of the nanoparticle such as size, shape, functionalization, surface charge, solubility, agglomeration, and aggregation state to improve their toxicological properties while retaining the desired functionality.[84] Handling procedures can also be improved, for example, using a nanomaterial slurry or suspension in a liquid solvent instead of a dry powder will reduce dust exposure. Engineering controls are physical changes to the workplace that isolate workers from hazards, mainly ventilation systems such as fume hoods, gloveboxes, biosafety cabinets, and vented balance enclosures. Administrative controls are changes to workers' behavior to mitigate a hazard, including training on best practices
for safe handling, storage, and disposal of nanomaterials, proper
awareness of hazards through labeling and warning signage, and
encouraging a general safety culture. Personal protective equipment must be worn on the worker's body and is the least desirable option for controlling hazards.
Personal protective equipment normally used for typical chemicals are
also appropriate for nanomaterials, including long pants, long-sleeve
shirts, and closed-toed shoes, and the use of safety gloves, goggles, and impervious laboratory coats. In some circumstances respirators may be used.
Nanotechnology has been making headlines in the medical field,
being responsible for biomedical imaging. The unique optical, magnetic
and chemical properties of materials on the Nano scale has allowed the
development of imaging probes with multi-functionality such as better
contrast enhancement, better spatial information, controlled bio
distribution, and multi-modal imaging across various scanning devices.
These developments have had advantages such as being able to detect the
location of tumors and inflammations, accurate assessment of disease
progression, and personalized medicine.
Silica nanoparticles- Silica nanoparticles
can be classified into solid, non-porous, and mesoporous. They have
large surface are, hydrophilic surface, and chemical and physical
stabilities. Silica nanoparticles are made by the use of the Stöber
process. Which is the hydrolysis of silyl ethers such as tetraethyl
silicate into silanols (Si-OH) using ammonia in a mixture of water and
alcohol followed by the condensation of silanols into 50–2000 nm silica
particles. The size of the particle can be controlled by varying the
concentration of silyl ether and alcohol or the micro emulsion method.
Mesoporous silica nanoparticles are synthesized by the sol-gel process.
They have pores that range in diameter from 2 nm to 50 nm. They are
synthesized in a water-based solution in the presence of a base catalyst
and a pore forming agent known as a surfactant. Surfactants are
molecules that present the particularity to have a hydrophobic tail
(alkyl chain) and a hydrophilic head (charged group, such as a
quaternary amine for example). As these surfactants are added to a
water-based solution, they will coordinate to form micelles with
increasing concentration in order to stabilize the hydrophobic tails.
Varying the pH of the solution and composition of the solvents, and the
addition of certain swelling agents can control the pore size. Their
hydrophilic surface is what makes silica nanoparticles so important and
allows them to carry out functions such as drug and gene delivery, bio
imaging and therapy. In order for this application to be successful,
assorted surface functional groups are necessary and can be added either
by the co-condensation process during preparation or by post surface
modification. The high surface area of silica nanoparticles allows them
to carry much larger amounts of the desired drug than through
conventional methods like polymers and liposomes. It allows for site
specific targeting, especially in the treatment of cancer. Once the
particles have reached their destination, they can act as a reporter,
release a compound, or be remotely heated to damage biological
structures in close proximity. Targeting is typically accomplished by
modifying the surface of the nanoparticle with a chemical or biological
compound. They accumulate at tumor sites through Enhanced Permeability
Retention (EPR), where the tumor vessels accelerate the delivery of the
nanoparticles directly into the tumor. The porous shell of the silica
allows control over the rate at which the drug diffuses out of the
nanoparticle. The shell can be modified to have an affinity for the
drug, or even to be triggered by pH, heat, light, salts, or other
signaling molecules. Silica nanoparticles are also used in bio imaging
because they can accommodate fluorescent/MRI/PET/ SPECT contrast agents
and drug/DNA molecules to their adaptable surface and pores. This is
made possible by using the silica nanoparticle as a vector for the
expression of fluorescent proteins. Several different types of
fluorescent probes, like cyanine dyes, methyl violegen, or semiconductor
quantum dots can be conjugated to silica nanoparticles and delivered
into specific cells or injected in vivo. Carrier molecule RGD peptide
has been very useful of targeted in vivo imaging.
Topically applied surface-enhanced resonance Raman ratiometric spectroscopy (TAS3RS)-
TAS3RS is another technique that is starting to make advancement in the
medical field. It is an imaging technique that uses Folate Receptors
(FR) to detect tumor lesions as small as 370 micrometers. Folate
Receptors are membrane bound surface proteins that bind folates and
folate conjugates with high affinity. FR is frequently overexpressed in a
number of human malignancies including cancer of the ovary, lung,
kidney, breast, bladder, brain, and endometrium. Raman imaging is a type
of spectroscopy that is used in chemistry to provide structural
fingerprint by which molecules can be identified. It relies upon
inelastic scattering of photons, which result in ultra high sensitivity.
There was a study that was done where two different surface enhanced
resonance Raman scattering were synthesized (SERRS). One of the SERRS
was a "targeted nanoprobe functionalized with an anti-folate-receptor
antibody (αFR-Ab) via a PEG-maleimide-succinimide and using the infrared
dye IR780 as the Raman reporter, henceforth referred to as αFR-NP, and a
nontargeted probe (nt-NP) coated with PEG5000-maleimide and featuring
the IR140 infrared dye as the Raman reporter." These two different
mixtures were injected into tumor bearing mice and healthy controlled
mice. The mice were imaged with Bioluminescence (BLI) signal that
produces light energy within an organism's body. They were also scanned
with the Raman microscope in order to be able to see the correlation
between the TAS3RS and the BLI map. TAS3RS did not show anything in the
healthy mice, but was able to locate the tumor lesions in the infected
mice and also able to create a TAS3RS map that could be used as guidance
during surgery. TAS3RS shows to be promising in being able to combat
ovarian and peritoneal cancer as it allows early detection with high
accuracy. This technique can be administered locally, which is an
advantage as it does not have to enter the bloodstream and therefore
bypassing the toxicity concerns circulating nanoprobes. This technique
is also more photostable than fluorochromes because SERRS nanoparticles
cannot form from biomolecules and therefore there would not be any false
positives in TAS3RS as there is in fluorescence imaging.
