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Nanostructured materials are single-phase or multiphase polycrystalline solids with a typical average grain size of a few nanometers, and usually less than 100nm. Such materials exhibit properties that are substantially different from, and often superior to those of conventional coarse-grained materials, due to their unique microstructure . Since the grain sizes are so small, a significant volume fraction of the atoms resides in grain boundaries. Thus, the material is characterized by a large number of interfaces in which the atomic arrangements are different from those of crystal lattice . At such small grain sizes, the surfaces start to dominate the bulk behavior of the material and, consequently, Nanostructured materials exhibit special and completely new and unexpected properties, often not observed in coarse-grained materials. Accordingly, Nanostructured materials have been shown to exhibit very unique functionalFigure 1. The classification of metal containing nanoparticles by the shape 
Nanostructured materials can be classified into different categories depending on the number of dimensions in which the material has nanometer modulations . Thus, they can be classified into zero, one, two and three dimensional structures as seen in Figure 1. Nanoparticles such as quantum dots are considered as zero dimensional structures. A layered or lamellar structure is a 1-dimensional nanostructure in which the magnitude of length and width are much greater than the thickness. On the other hand, a 2-dimensional rod-shaped is a nanostructure where the length is substantially larger than the width or diameter. The most common of the nanostructures, however is equiaxed 3-dimensional structures such as nanostructured bulk materials and nano composites .
The nanostructured materials may contain crystalline, quasicrystalline, or amorphous phases and can be metals, ceramics, polymers, or composites. If the grains are made up of crystals, the material is called nanocrystalline. On the other hand, if they are made up of a quasicrystalline or amorphous (glassy) phases, they are termed nano quasicrystals and nano glasses, respectively. Gleiter  has further classified the nanostructured materials according to the composition, morphology, and distribution of the nanocrystalline component.
This report will focus on the zero-dimensional structures known as Nanoparticles, particularly demonstrating magnetic functional behavior - leading them to be generally classified as Magnetic Nanoparticles. The next section will introduce the general characteristics and the behavior of such Nanoparticles.
1.2 Magnetic Nanoparticles
Among many of known nanomaterials, the special position belong to those, in which isolated magnetic nanoparticles are divided by dielectric nonmagnetic medium. These nanoparticles present giant magnetic psudoatoms with the huge overall magnetic moment and "collective spin" . In this regard nanoparticles fundamentally differ from the classic magnetic materials with their domain structure. As a result of recent investigations, the physics of magnetic phenomena - nanomagnetism was developed. Nanomagnetism advances include superparamagnetism, ultrahigh magnetic anisotropy and coercive force, and giant magnetic resistance.
Currently, unique physical properties of magnetic nanoparticles are under intensive research . A special place belongs to to the magnetic properties in which the difference between a massive (bulk) material and a nonmaterial is especially pronounced. In particular, it was shown that magnetization and the magnetic anisotropy of nanoparticles could be much greater than those of a bulk specimen, while differences in the Curie or Neel temperatures between nanoparticle and the corresponding microscopic phases reach hundred of degrees. The magnetic properties of nanoparticles are determined by many factors, the key of these including the chemical composition, the type and the degree of defectiveness of the crystal lattice, the particle size and shaper, the morphology, the interaction of the particle with the surrounding matrix and the neighboring particles . By changing the nanoparticle size, shape, composition and structure one can control to an extent the magnetic characteristics of the material based on them. However, these factors cannot always be controlled during the synthesis of nanoparticles nearly equal in size and chemical composition; therefore, the properties of nanomaterials of the same type can be markedly different.
2 Iron Oxide nanoparticles for biomedical applications
In the last decade, nanotechnology has developed to such an extent that it has become possible to fabricate, characterize and specially tailor the functional properties of nanoparticles for biomedical applications and diagnostics . As intermediates between the molecular and the solid states, inorganic nanoparticles combine chemical accessibility in solution with physical properties of the bulk phase . They are thus ideal elements for the construction of nanostructured materials and devices with adjustable physical and chemical properties . The application of small iron oxide particles in in-vitro diagnostics has been practiced for nearly 40 years  and in the last decade, increased investigations with several types of iron oxides have been carried out in the field of nanosized magnetic particles, among which magnetite is a very promising candidate since its biocompatibility has already been proven .
Magnetite, Fe3O4, is a common magnetic iron oxide that has a cubic inverse spinel structure with oxygen forming an FCC closed packing and Fe cation occupying interstitial tetrahedral and octahedral sites . With proper surface coating, these magnetic nanoparticles can be dispersed intro suitable solvents, forming homogeneous suspensions, called ferrofluids. Such a suspension can interact with an external magnetic field and be positioned to a specific area, facilitating magnetic resonance imaging for medical diagnosis and AC magnetic field-assisted cancer therapy .
For any biomedical application, the particles must have combined properties of high magnetic saturation, biocompatibility and interactive functions at the surface. The surfaces of these particles could be modified through the creation of few atomic layers of organic polymer or inorganic metallic or oxide surfaces, suitable for further functionalization by the attachment of various bioactive molecules . For magnetic nanoparticles to be used in in vitro and in vivo applications, should have suitable surface characteristics . In all cases, superparamagnetic particles are of interest because they do not retain any magnetism after removal of magnetic field .
2.2 Synthesis and Structure of magnetic Iron Oxide nanoparticles
Iron oxides (either Fe3O4 or Î³-Fe2O3) can be synthesized through the co-precipitation of Fe2+ and Fe3+ aqueous salt solutions by addition of a base . The type of salts used would be control the size, shape and composition of nanoparticles (e.g. chlorides, sulphates, nitrates, perchlorates, etc.), Fe2+ and Fe3+ ratio, pH and ionic strength of the media.
Conventionally, magnetite is prepared by adding a base to an aqueous mixture of Fe2+ and Fe3+ chloride at a 1:2 molar ratio. The overall reaction may be written as follows:
Fe2+ + 2Fe3+ +8OH- --> Fe3O4 + 4H2O (1)
The oxidation of Fe3O4 would critically affect the physical and chemical properties of the nanosized magnetic particles. In order to prevent them from possible oxidation in air as well as from agglomeration, Fe3O4 nanoparticles produced by reaction (1) are coated with organic or inorganic molecules during the precipitation process .
Gupta et.al.  have utilized water-in-oil microemulsions to synthesize superparamagnetic iron oxide nanoparticles in narrow size range with uniform chemical and physical properties. Highly mono dispersed ironFigure 2. Structure of reverse micelles formed by dissolving AOT, a surfactant, in n-hexane. The inner core of the reverse micelle is hydrophilic and can dissolve water-soluble compounds. The size of these inner aqueous droplets can be modulated by controlling the parameter Wo (Wo 1â„4 [water]/[surfactant]) .
oxide nanoparticles were synthesized by using the aqueous core of aerosol-OT (AOT)/n-hexane reverse micelles (w/o microemulsions) as can be seen in Figure 2.
The hydrophilic compounds, salts and etc can be dissolved by reverse micelles that has aqueous inner core. A deoxygenated aqueous solution of the Fe3+ and Fe2+ salts (molar ratio 2:1) was dissolved in the aqueous core of the reverse micelles formed by AOT in n-hexane. By using a deoxygenated solution of sodium hydroxide, chemical precipitation was achieved. Smaller and more uniform particles were then prepared by precipitation of magnetite at low temperature in the presence of nitrogen gas. This is shown in the schematics in Figure 3 below.
2.3 Surface modification of magnetic nanoparticles for biomedical applications and their effect on stability and magnetization
In the preparation and storage of nanoparticles in colloidal form, the stability is of utmost importance. Ferrofluids are colloidal suspensions of magnetic particles, forming magnetizable fluids that remain liquid in the most intense magnetic fields and find widespread applications. As a result of their composition, magnetic fluids possess a unique combination of fluidity and the capability to interact with a magnetic field . The lack of any surface coating results in the magnetic iron oxide particles to have hydrophobic surfaces with a large surface area to volume ratio. The hydrophobic interactions betweenFigure 3. Schematics of preparing highly monodispersed iron oxide nanoparticles inside the w/o microemulsions droplets. Iron salts were dissolved inside the aqueous cores of reverse micelles and precipitated using alkali solutions to get the particle of desired size .
the particles results in the particles agglomerating and forming large clusters, which leads to an increase in particle size. These clusters, then, exhibit strong magnetic dipole-dipole attractions between them and show ferromagnetic behavior . When two large-particle clusters approach one another, each of them comes into the magnetic field of the neighbor.
Besides the arousal of attractive forces between the particles, each particle is in the magnetic field of the neighbor and gets further magnetized . Increased aggregation in properties of the nanoparticles are caused by the adherence of remnant magnetic particles which results in a mutual magnetization.
Since particles are attracted magnetically, in addition to the usual fluctuation due to Van der Waals force, surface modification is often indispensable. Usually, a very high requirement of density for coating is desirable for effective stabilization of iron oxide nanoparticles. To prevent aggregation of the nanoscale particulate, stabilizers such as a surfactant or a polymer is usually added at the time of preparatFigure 4. Scheme showing different strategies for fabrication and surface modification of magnetic iron oxide nanoparticles. Smaller and more uniform nanoparticles can be prepared inside the aqueous droplets of reverse micelles .
ion. Most of these polymers adhere to surfaces in a substrate-specific manner . Scheme showing different strategies for fabrication and surface modification of magnetic iron oxide nanoparticles is shown in Figure 4 below. Although coating materials for nanoparticles include inorganic, organic and polymeric materials, this report will however only focus on non-polymeric organic stabilizers.
2.3.1 Surface modification with non-polymeric organic stabilizers
To stabilize the nanoparticles in organic solvents, Sahoo et al.  have reported the surface derivatization of magnetite by oleic acid, lauric acid, dodecylphosphonic acid, hexadecylphosphonic acid, dihexadecylphosphonic acid etc. They found that to obtain thermodynamically stable dispersions of magnetic nanoparticles, alkyl phosphonates and phosphates could be used. It has also been reported that these ligands form a quasi-bilayer structure with the primary layer strongly bonded to the surface of nanoparticles. This was based on the results obtained from the temperature and enthalpy desorption studies done by them . The ferro fluids, frequently dispersed in hexadecane (HD: C16H34) as the carrier medium, may be stabilized by various long-chain surfactants, the classic example being oleic acid (CH3(CH2)7CH=CH(CH2 7CO2H), which has a C18 (oleic) tail with a cis-double-bond in the middle, forming a kink . Since the use of polymers leads to thick surface layers, Portet et al.  have developed monomeric organic molecules as coating materials. Protein absorption by these small molecules is mainly prevented by this homogeneous coating of the entire iron oxide core. Phosphorylcholine (PC)-derived polymers are known to protect prosthesis against protein contamination, but pure PC coatings do not allow colloidal stability at physiological pH .
3 Biomedical application of magnetic nanoparticles
Magnetic nanoparticles offer some attractive possibilities in medicine and this report will briefly discuss four such application. Living organisms are built of cells that are typically 10Î¼m in diameter. However, the cell parts are much smaller and in the sub-micron size domain. First advantage in medicine is that the nanoparticles have controllable size ranging from a few nanometers up to tens of nanometers, which places them at dimensions that are smaller than those of a cell (10-100Î¼m), or comparable to size of a virus (20-450nm). This means that they can "get close" to a biological entity of interest. Moreover, they can be coated with biological molecules to make them interact with or bind to a biological entity, thereby providing a controllable means of "tagging" or addressing it .
Second, if nanoparticles are magnetic, they can be manipulated by an external magnetic field gradient. This "Action at a distance," combined with intrinsic penetrability of magnetic fields into human tissue, opens up many applications involving the transport and immobilization of magnetic nanoparticles, or of magnetically tagged biological entities. In this way, they can be made to deliver a package, such as anticancer drug, to a targeted region of the body such as a tumor .
Third, the magnetic nanoparticles can be made to resonantly respond to a time-varying magnetic field, with advantageous results related to the transfer of energy from the exciting field to the nanoparticle. For example, the particle can be made to heat up, which leads to their use as hyperthermia agents, delivering toxic amounts of thermal energy to targeted bodies such as tumors.
Lastly, cell labeling with ferro substances is an increasingly common method for in vivo cell separation  as the labelled cells can be detected by MRI. Gupta et.al  have discovered a route to deriving superparamagnetic nanoparticles with various targeting proteins such as lactoferrin, transferrin, ceruloplasmin,Figure 5. Scheme of derivation of superparamagnetic iron oxide nanoparticles either with targeting ligands such as lactoferrin (Lf) or ceruloplasmin (Cp) and their targeting to human fibroblasts. The derived nanoparticles act as cellular markers that are targeted at the surface receptors expressed on human fibroblasts surface without being internalized 
etc., that bind strongly to surface receptors such that phagocytosis is inhibited as illustrated in Figure 5 below.
The concept of drug delivery using magnetic nanoparticles greatly benefit from the fact that nanotechnology has developed to a stage that it makes possible not only to produce magnetic nanoparticles in a very narrow size distribution with superparamagnetic properties but also to engineer particles surfaces to provide site-specific delivery of drugs. Due to its strong magnetic properties, Magnetite was used first in biology and then in medicine for the magnetic guidance of particle systems for site-specific drug delivery. Moreover, It is used for magnetic separation of biological products and cells as well as. The size, charge, and surface chemistry of magnetic particles could strongly influence their bio-distribution . Moreover, magnetic properties depend strongly on the size of magnetite particles and in the last decade, the activities in the clinical applications of magnetic carriers and magnetic particles have been very high, because the needs of better diagnostic procedures on one side and better treatment modalities are, on the other hand, strongly increasing . Particles can target specific cell types when it is attached by a specific antibody i.e. macrophages having receptors expressed on their surfaces. Where appropriate, magnetic field can be used to focus the macrophages or divert them away from tissue in bid to modify inflammation. This also includes other biological applications, such as cell separation, in which the improvement of the success rate is of great importance for the classification and handling of cells. The growth of the biomedical industry and the improvement in the quality of life in the population can be realized with the successful development in this area.