Nanotechnology is a known field of research since last century. Since ‘‘nanotechnology” was presented by Nobel laureate Richard P. Feynman during his well famous 1959 lecture ‘‘There’s Plenty of Room at the Bottom, there have been made various revolu-tionary developments in the field of nanotechnology. Nanotechnology produced materials of various types at nanoscale level. Nanoparticles(NPs) are wide class of materials that include particulate substances, which have one dimension less than 100 nm at least (Laurent et al.,2010). Depending on the overall shape these materials can be 0D,1D, 2D or 3D. The importance of these materials realized when researchers found that size can influence the physiochemical properties of a substance e.g. the optical properties. A 20-nm gold (Au), platinum (Pt), silver (Ag), and palladium (Pd) NPs have characteristic wine red color, yellowish gray, black and dark black colors, respectively. Fig. 1shows an example of this illustration, in which Au NPs synthesized with different sizes. These NPs showed characteristic colors and properties with the variation of size and shape, which can be utilized in bio imaging applications. As Fig. 1indicates, the color of the solution changes due to variation in aspect ratio, nano shell thickness and % gold concentration. The alteration of any of the above discussed factor influences the absorption properties of the NPs and hence different absorption colors are observed. NPs are not simple molecules itself and therefore composed of three layers i.e. (a) The surface layer, which may be functionalized with a variety of small molecules, metal ions, surfactants and polymers. (b)The shell layer, which is chemically different material from the core in all aspects, and (c) The core, which is essentially the central portion of the NP and usually refers the NP itself. Owing to such exceptional characteristics, these materials got immense interest of researchers in multidisciplinary fields. Fig. 2 shows scanning electron microscopy (SEM) and transmittance electron microscope(TEM) images of mesoporous and nonporous methacrylate functionalized silica (MA-SiO2). Mesoporousity imparts additional characteristics in NPs. The NPs can be employed for drug delivery, chemical and biological sensing, gas sensing, CO2capturing and other related applications. In this review article, we provide a general overview on the different types, synthesis methods, characterizations, properties and applications of NPs. The last section is also provided with the future aspect sand recommendations
As shown in Fig. 2, viruses are small enough to be inhabitants of the nano world whereas bacteria are much larger, being typically over 10 μm (10,000 nm) in size, though they are packed with “machinery” that falls into the size range of the nano world (see Chapter 6, Section 6.1.3). Going down in size, the figure shows typical sizes of metal particles, containing ∼۱۰۰۰ atoms that can be used to produce advanced materials. The properties of these (per atom) deviate significantly from the bulk material, and so assembling these into macroscopic chunks produces materials with novel behavior. Finally, the lower edge of the nanoworld is defined by the size of single atoms, whose diameters vary from 0.1 nm (hydrogen atom) to about 0.4 nm (uranium atom). We cannot build materials or devices with building blocks smaller than atoms, and so these represent the smallest structures that can be used in nanotechnology
Fig2. The size range of interest in nanotechnology and some representative objects.
A nanoparticle, as one could guess, is a particle that is so small that it must be measured on the nanoscale. It is an exciting development in biotechnology, as it has only been recently achievable due to advances in equipment and supporting research that allow for its precise synthesis. These particles are multifaceted, applicable, to many aspects of healthcare, such as combating diseases like cancer. Even though nanoparticles can vary in their specificity and purpose, the general idea behind the development of nanoparticles is simple. By making such a small particle, transport throughout the body is made easier, thereby allowing it to address the target health issue faster and better. That type of reach would advance healthcare monumentally and could even be the new standard form medicine will take. Nanoparticle development is an effort to truly optimize medicine and its delivery, and has already been demonstrated to be a promising alternative to conventional oral or injection-based medicinal techniques, which have issues like low potency and high solubility(Scherrmann, J. 2002)
There are many types of NP platforms with differing size, shape, compositions, and functionalities. Furthermore, each type of NPs can potentially be fabricated using different techniques, such as both nanoprecipitation and lithography for polymeric NPs. While it is not within this manuscript’s scope to discuss the differences in NP platforms and their fabrication in detail, we will discuss the major characteristics and functionalities of each NP that are relevant for biomedical research.
The first NP platform was the liposomes. Liposomes were first described in 1965 as a model of cellular membranes. Since then, liposomes have moved from a model in biophysical research to one of the first NP platforms to be applied for gene and drug delivery. Liposomes are spherical vesicles that contain a single or multiple bilayered structure of lipids that self-assemble in aqueous systems. Unique advantages imparted by liposomes are their diverse range of compositions, abilities to carry and protect many types of bio molecules, as well as their biocompatibility and biodegradability. These advantages have led to the well-characterized and wide use of liposomes as transfection agents of genetic material into cells (lipofection) in biology research. Lipofection generally uses a cationic lipid to form an aggregate with the anionic genetic material. Another major application of liposomes is their use as therapeutic carriers since their design can allow for entrapment of hydrophilic compounds within the core and hydrophobic drugs in the lipid bilayer itself. To enhance their circulation half-life and stability in vivo, liposomes have been conjugated with biocompatible polymers such as polyethylene glycol (PEG). Liposomes can also be functionalized with targeting ligands to increase the accumulation of diagnostic and therapeutic agents within desired cells. Today, there are twelve clinically approved liposome-based therapeutic drugs.
Albumin-bound NPs (nab) uses the endogenous albumin pathways to carry hydrophobic molecules in the bloodstream. Albumin naturally binds to the hydrophobic molecules with non-covalent reversible binding, avoiding solvent-based toxicities for therapeutics. As a result, this platform has been successfully adapted as drug delivery vehicle. Abraxane, a 130-nm nab paclitaxel was approved by the FDA in 2005 for the treatment of metastatic breast cancer. Abraxane concentrates in cells through albumin receptor (gp60)-mediated transport in endothelial cells. It may also target the albumin-binding protein SPARC (secreted protein acidic and rich in cysteine), which is overexpressed in certain tumors. Further understanding of the mechanism of action may lead to better targeting and development of novel therapeutics using the nab platform.
Polymeric NPs formed from biocompatible and biodegradable polymers have been extensively investigated as therapeutic carriers. Polymeric NPs are formulated through block-copolymers of different hydrophobicity. These copolymers spontaneously assemble into a core-shell micelle formation in an aqueous environment. Polymeric NPs have been formulated to encapsulate hydrophilic and/or hydrophobic small drug molecules, as well proteins and nucleic acid macromolecules. The NP design can allow for slow and controlled release of drug at target sites. Polymeric NPs are usually able to improve the safety and efficacy of the drugs they carry. Functionalizing polymeric NPs with targeting ligands for improved drug delivery has been an important area of investigation since polymeric NPs are unique in their ability to be tailored prior to particle assembly. The incorporation of targeting ligands on the NPs can lead to their increased uptake along with their cargo, leading to enhanced therapeutic outcomes.
Another type of polymeric NP is dendrimers. Dendrimers are regularly branched macromolecules made from synthetic or natural elements including amino acids, sugars, and nucleotides. They have a central core, interior layers of branches, and an exterior surface. The varied combination of these components can yield dendrimers of well-defined size, shape, and branching length/density. As a result of their unique design, dendrimers can be developed as sensors as well as drug and gene delivery carriers. Dendrimers can be loaded with small molecules in the cavities of the cores through chemical linkage, hydrogen bond, and or hydrophobic interaction. The exterior surface can also be readily modified to produce chemical functional groups for molecular targeting groups, detecting and imaging agents, and therapeutic attachment sites.
Iron oxide NPs are widely studied as a passive and active targeting imaging agent as they are mainly super paramagnetic. The super paramagnetic iron oxide NP (SPION) generally have an iron oxide core with a hydrophilic coat of dextran or other biocompatible compound to increase their stability. The most widely used SPIONs consist of a magnetite (Fe3O4) and/or maghemite (γFe2O3) core. These NPs exhibit size-dependent super paramagnetism, which allows them to become magnetized with the application of an external magnetic field and exhibit zero net magnetization upon removal of the magnetic field. SPIONs have been successfully used as T2-weighted magnetic resonance (MR) contrast agents to track and monitor cells. SPIONs have several advantages over conventional gadolinium-chelate contrast agents including decreased toxicity and increased imaging sensitivity and specificity. SPIONS can also be degraded to iron and iron oxide molecules that are metabolized, stored in cells as ferritin, and incorporated into hemoglobin. Currently, two SPIO agents, ferumoxides (120–۱۸۰ nm) and ferucarbotran (60 nm) are clinically approved for MRI. SPIONs have also been used in molecular imaging applications such as the detection of apoptosis and gene expression. SPIONs can be functionalized with magnetic, optical, radionuclide and specific targeting ligands for multimodal imaging. They can also potentially be used as non-invasive diagnostic tools and as drug delivery vehicles.
First discovered in 1980, quantum dots (QDs) are semiconductor particles that are less than 10 nm in diameter. QDs display unique size-dependent electronic and optical properties. Most QDs studied consist of a cadmium selenide (CdSe) core and a zinc selenide (ZnS) cap. The absorption spectra of these particles are very broad and emission is confined to a narrow band. QDs can also emit bright colors, have long lifetimes, high efficiencies and are stable against photobleaching. They can be generated to have different biochemical specificities and can be simultaneously excited and detected. As a result, QDs have several significant advantages over many organic fluorophore dyes for optical applications. They are widely used in biological research as fluorescence imaging tools for applications such as cell labeling and biomolecule tracking. The small size of quantum dots also enables them to be suitable for biomedical applications such as medical imaging and diagnostics.
Gold NPs offer many size-and-shape dependent optical and chemical properties, biocompatibility, and facile surface modification. Gold NPs can strongly enhance optical processes such as light absorption, scattering, fluorescence, and surface-enhanced Raman scattering (SERS) due to the unique interaction of the free electrons in the NP with light. These properties have enabled the realization of gold NPs in many applications such as biochemical sensing and detection, biological imaging, diagnostics, and therapeutic applications. Sensing techniques include the use of gold NPs in colorimetric arrays and the use of gold NPs as substrates in SERS to significantly enhance Raman scattering, allowing for spectroscopic detection and identification of proteins and single molecules at the NP surface. Gold NP probes have also been used to detect heart disease and cancer biomarkers. They can also transform absorbed light into heat and therefore, have high potential for infrared phototherapy.