On considering the developments and achievements of nanotechnology in the past few years, scientists and researchers believe that it is the most significant, promising technology of the twenty-first century. Nanotechnology can be defined as the science of fabricating materials or devices at the atomic or molecular level ranging from 1 nm to 100 nm in at least one of the three dimensions. This technology mainly focuses on characterisation, fabrication, and manipulation of biological and non-biological structures smaller than 100 nanometres . Generally, biological and non-biological structures on such a small scale (nanoscale) have been studied to have unique and novel functional properties .
Nanotechnology is a multidisciplinary field which encompasses a wide range of applications using bio-nanomaterials in engineering or engineered nanomaterials in biology and medicine. The prospective outcomes of this nanoscale technology have been recognized by many industries, and commercial products are already being manufactured, such as in the microelectronics, aviation, health and personal care industries . Human health-related medical technology will most likely be the first beneficiary of the fruits of nanotechnology. In medical field, simple structures can be made custom-designed to meet a very specific purpose. Nanotechnology when applied to medical field forms the core for an entirely new branch of science called nanomedicine. As per the Institute of Nanotechnology based at Scotland, nanomedicine is the application of nanotechnology in medical imaging, lab-on-a-chop, quantum dots and other novel diagnostic tools, biosensors, regenerative medicine, advanced and smart medical materials, drug targeting and delivery systems, nano-bio-electronic interfaces and novel devices.
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To get a perspective of the scale used in nanotechnology, the size of selected nanotechnology materials is estimated and given in table 1.1.
1 - 100 nm
Quantum Dot (CdSe)
Table 1.1. Nanomaterials and relevant sizes.
In comparison, representative structures and materials found in nature are typically referenced to have the respective dimensions as given in table 1.2.
Structures & Materials
5 - 5- nm
75 - 100 nm
Materials internalized by cell
< 100 nm
1,000 - 10,000 nm
Table 1.2. Naturally found materials and relevant sizes.
The size domains of components involved with nanotechnology are similar to that of biological structures. For example, a quantum dot is about the same size as a small protein (< 10 nm) and drug-carrying nanostructures are the same size as some viruses (< 100 nm). Because of this similarity in scale and certain functional properties, nanotechnology is a natural progression of many areas of health-related research such as synthetic and hybrid nanostructures that can sense and repair biological lesions and damages just as biological nanostructures (e.g. WBC and wound-healing molecules).
Nano is the continued miniaturization beyond micro. However due to a number of scientific principles becoming dominant at the nanoscale, nanomaterials can have very different properties than bulk materials. This includes materials that are stronger, lighter, more electrically conductive, superparamagnetic, tunable optical emission, more porous, better thermal insulating, and less corrosive. Nanomaterials have the potential to solve unique biological challenges not currently possible, such as having inorganic materials detect electrical changes from biological molecules and react in a manner that detects or treats a disease.
As well, miniature devices and systems that operate at a smaller scale than micro can bring significant improvements in the way microscale devices work. This includes higher throughput DNA sequences that can reduce the time for drug discovery and diagnostics. Another example is tiny fluidic systems that more efficiently conduct chemical experiments since fluids move through micro and nanoscale pipes with laminar flow, which avoids turbulence and mixing.
Transforming materials from the micro level to the nano level is referred to as top-down. At the other extreme where atoms and molecules at the pico level are constructed or self-assembled to the nano level, this is referred to as bottom-up. As life itself creates and uses molecular materials and devices, nanotechnology will provide great insights in life science concepts, such as how molecular materials self-assemble, self-regulate, and self destroy. The scope of nanoscience and technology is enormous and overlaps with many traditional sciences. Although only a subset of nanoscience applies to life processes, the potential for breakthroughs is enormous and is being pursued on multiple fronts.
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Again when moving to nanomedicine, it has a big future because it is a way to design small devices such as sensors, particles, and nanobots that can go inside our body and do what we program them to do . Nanomedicine embraces five main sub-disciplines: analytical tools, nanoimaging, nanomaterials and nanodevices, new therapeutics and medicine delivery systems, and clinical, regulatory, and toxicological issues. It can be said that the potential of nanotechnologies raises great hopes . The systematic linkage of these five sub-disciplines in healthcare is given in figure 1.1. The short term potential benefits include therapies for cancer, antiviral and antifungal agents, arteriosclerosis, diabetes, and chronic lung diseases; while the long term benefits include gene therapy and cell repair .
Figure 1.1. Nanomedicine: towards healthcare.
In healthcare sector, nanoparticles are widely used for various purposes. A selection of few current and future applications using nanoparticles are given in table 1.3.
Ag-based antibacterial wound dressings
Au for biolabeling and detection
MRI contrast agents using superparamagnetic Fe2O3
Sunscreens using ZnO and TiO2
Molecular tagging using CdSe quantum dots
Drug carriers for drugs with low water solubility
Coatings for implants such as hydroxyapatite
Marker particles for use in assays
Nanocrystalline drugs for easier absorption
Nanospheres for inhaling drugs currently injected using bio-compatible Si
Bone growth promoters
Virus detection using quantum dots
Magnetic particles for the repair of the human body with prosthetics or artificial replacement parts
Fullerenes based anti-oxidant drugs
Table 1.3. Applications of nanoparticles in healthcare/medical sector .
In early 2000s, the global nanomedicine market was estimated at $53 billion and is forecast to increase at a compound annual growth rate of 13.5% to reach more than $100 billion in 2014 . In a recent report released on June 29, 2009, the nanomedicine market is expected to exceed $160 billion in the next five years .
The rest of this essay will discuss in detail about the basics of functional nanomaterials including classifications, concepts and techniques followed by evidence based review on their medical applications. Further, it will give a brief note on the upcoming new challenges and future research directions in the summary and outlook section.
Nanotechnology deals with new materials such as zero dimensional nanoparticles and one dimensional structures that are expected to revolutionize various fields including biology and medicine. Having a size of 1 nm to 100 nm and a high surface area to volume ratio, nanoscale materials can be combined with host materials to change dramatically the properties of the bulk material making them smart and applicable in many high-tech areas . Smart materials and devices with advantages of high performance, small size, and low cost may be developed on nanoscale particles .
2.1. Classification of Nanomaterials
There are many systems for classification of nanomaterials. The two most generally used systems are dimension of material-based system and characteristic of material-based system . Concerning dimension of material-based system, there are three groups of nanostructure materials. The first group is one-nano dimension. A good example is nanofilm. The second group is two-nano dimensions. This group has a common tubular fiber structure. Examples of nanostructure materials in this group are nanofilter, nanowire, and carbon nanotube. The third group is three-nano dimensions. Examples for this group are nanoparticles, nanopowder, nanocapsule, quantum dot, nanopore, nanostructure, dendrimer, and fullerene [3,9].
Concerning the characteristics of the material-based system, six main groups are organic nanoparticles, inorganic nanoparticles, organic/inorganic hybrids, carbon-based nanomaterials, liposome and biological nanoparticles [3,9]. Examples of nanomaterials classified by characteristic of material-based system are given in table 2.1. The structures of different nanomaterials are portrayed in figure 2.1.
Iron oxide nanoparticles
Protein and peptide-based nanoparticles with other biological components
Table 2.1. Nanomaterials classified by characteristic of material-based system [3,9].
Figure 2.1. Structures of different nanomaterials.
2.2. Nanomaterials made for Medicine
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Nanomaterials is a general term that includes; nanoscale materials where the material itself is at the nanoscale size; nanophase materials, which are hybrid materials that have a nanoscale phase or component; and nanostructured materials, where the material structure has nanoscale size or features. A characteristic of nanomaterials is their improved properties compared to their bulk states. The new properties and large surface areas per volume of material have been used to develop functional nanomaterials for cancer diagnosis and therapeutics ranging from delivering chemotherapy molecules in nano-sized capsules to functional nanomaterials that deliver thermal and radiotherapy at specific targeted sites. A review of various nanotechnologies in cancer therapy and diagnostics is given by Hede and Huilgol . Four subareas of functional nanomaterials that will be important to creating nanomedicine are discussed below. Several of these ideas come from National Science Foundation initiatives .
2.2.1. Artificial Biomaterials and Systems
Artificial nanobiomaterials and enhanced systems are of interest to regenerate tissue, bone, and organs. Also of interest are implants that can grow and adapt to the body for applications like paediatric orthopaedics .
2.2.2. Nanomaterials for Sustainability in the Body
Materials and biomanufacturing research should consider sustainability in the body in terms of wear, toxicity, and energy supply. Examples include fundamental research on synthesis, properties and mechanisms of biologically friendly nanocoatings, chemicals, and materials, materials for energy harvesting, thermo-electric conversion, new energy storage methods like biological fuel cells, biogalvanic batteries, and biodegradable metals for implants, sensors, and drug delivery vectors that can dissolve in the body without toxicity when they are no longer needed .
2.2.3. Smart Nanomaterials for Biology and Medicine
Smart nanostructured materials and biomedical devices have properties that can be changed by external stimuli. These stimuli include stress, temperature, moisture, pH, electric or magnetic fields, and biological stimuli for use in sensing and actuation. Applications of such adaptive materials and systems range from the ability to control artificial muscles to sense different physiological variables inside the body, possibly including temperature, pressure, acceleration, strain, chemicals, proteins, microbes, cells, axon potentials, and almost any physical variable. These smart or responsive materials might also have the potential to be self-heating and self-regenerating like the human body .
2.2.4. Nanoparticles for Cancer Therapy
Thermal, magnetic, chemical, and radioactive nanoparticles may be used to image and kill cancer cells. The most common nanoparticle used in cancer research is gold nanoshells, which have already entered clinical trials. Jennifer West and Naomi Halas at Rice University have constructed gold nanoshells that can absorb light or scatter it . The nanoshells are designed to absorb infrared light and image cancer cells or heat up. When they heat up, they will cauterize cancer cells. The nanoshells are injected into the patient's bloodstream and they pass through the leaky vascularate and collect in the tumor. An optical fiber inserted into the tumor illuminates the nanoshells with infrared light. The light heats the nanoshells and kills the tumor. Clinical trials are now being conducted at three medical centers in Texas on patients with head and neck cancers. An advantage of photothermal ablation is that no drug is used. Drug-free therapy lessens the potential for toxicity. But there may be chances for toxicity from the particle itself. Nanospectra Biosciences will be the market leader in commercializing the nanoshells .
Another type of thermal treatment of cancer is done using iron-oxide nanoparticles. These particles are injected directly into the tumor and are heated using alternating magnetic fields that are easily tolerated by patients. Clinical trials of the magnetic anticancer nanoparticles are conducted by MagForce Nanotechnologies in Berlin, Germany. This technique reportedly is not toxic and is promising for use against glioblastoma brain cancer and prostate cancer .
Thermal treatment may not be useful in all circumstances. An alternative is the use of nanoparticles that carry drugs. Multifunctional nanoparticles are also being investigated that can deliver drugs, radiation, and thermal treatment. The particle might also be used for imaging. The multifunctional mode may have the advantage that if one mode fails, another might succeed.
2.3. Medical Applications of Functional Nanomaterials
As the name suggests, the definition of functional nanomaterials reflects the ability of a nanomaterial to perform a certain 'function' under a determined stimulus . In medical field, the functional nanomaterials are widely used in diagnostics, sensing, imaging, therapeutics, etc..
2.3.1. Application of Functional Polymers
Polymer is a complex generated from a monomer. The polymer can be seen in multiple sizes. Almost everything we use in our daily life has a polymer nature. In nanoscience, polymers play a vital role. The polymers in nanolevel are called nanopolymers, which possesses the properties of nanomaterials: quantum effect, surface effect and interface effect . Polymers are applied in various biomedical fields such as tissue engineering, bone repair, prostheses, medical implants, dentistry, ophthalmology, etc.. Controlled release of drugs into the host can be successfully achieved by polymer-based drug delivery systems . Many different ways are employed in the preparation of polymer micro- and nanoparticles from monomers.
Emulsion polymerization brings particles of about 50-200 nm in diameter. This method produces regular, spherical particles.
Emulsifier Free Emulsion Polymerisation
Emulsifier free emulsion polymerization produces particles of about 100 nm - 1000 nm (0.1-1.0 micron). This method produces regular, spherical particles.
Dispersion polymerization produces particles in the region of 0.3-10 micron. This method produces regular, spherical particles.
Suspension polymerization brings about the formation of particles of about 20 micron to 2 mm. The gap in the 10-20 micron region may be filled by either seeded polymerization or by more elaborately performed suspension polymerization. This method produces regular, spherical particles.
Precipitation polymerization gives irregularly shaped particles in the range of 0.1-10 micron. It is useful only if low molecular weights of the polymer and polydispersity of the particles do not adversely impact the intended applied usage of the product.
Seed polymerization is the polymerization aiming at seeding of particles. This can result in a seeded polymer.
Anionic polymerization means polymerization in which the catalysts are Lewis bases, such as alkali metals.
Cationic polymerization means polymerization in which the catalysts are Lewis acids, such as acidic metals.
Free Radical Polymerization
Free radical polymerization means polymerization in which the catalysts are free radicals.
The nanopolymer can be a one-dimensionsal nanopolymer, a two-dimensional nanopolymer or a three-dimensional nanopolymer. The important nanopolymers are discussed further.
Nanofilm is a very thin film with a thickness of less than 100 nm. It plays an important part in the development of nanofilm-based disarmer. At present, the field of polypeptide multilayer nanofilm research flourishes where the study of protein structure and function shares a border with the development of polyelectrolyte multilayers . The nanofilm is accepted for its usefulness for the fabrication of process in the development of a biodevice.
In 2006, Yasuda et al. reported on biocompatibility of nanofilm-encapsulated silicone and silicone-hydrogel contact lenses. The study showed that the encapsulation of a highly oxygen-permeable contact lens by a nanofilm with an imperturbable surface state decreased the unwanted effects of the contact lens . In another study conducted in 2005, Srivastava et al. studied the stable encapsulation of an active enzyme by applied usage of multilayer nanofilm coatings to alginate microspherical objects. In this work, layer by layer self-assembly was explored as a potential way to bring a diffusion barrier to encapsulated glucose oxidase alginate microspherical objects, fabricated using an emulsification method . Four probe measurements of the in-plane thermoelectric properties of nanofilms were discussed in a work done by Mavrokefalos et al. in 2007. They reported a method based on a suspendedmicrowave for four-probe measurements of the Seebeck coefficient, thermal conductivity, electrical conductivity, and thermoelectric figure of merit of patterned indium arsenide nanofilms integrated on the microdevice .