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# A Review on Nanoferrites in Biomedical Applications

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Introduction In recent years, Nanotechnology has become an intense area of scientific research due to its potential applications in the field of biology & biomedicines, optics and electronics, catalysis and many others. Nanotechnology deals with the study nanoparticles having at least one dimension roughly between 1 to 100 nm. Nanoparticles are usually distinguished from microparticles (1-1000μm), fine particles (sized between 100 and 2500nm), and coarse particles (ranging from 2500 to 10,000nm), because their smaller size drives very different physical or chemical properties, like colloidal properties and optical or electrical properties. Being more subject to Brownian movement, they usually do not sediment, like colloidal particles. Nanoparticles have a number of properties that distinguish them from bulk materials simply by virtue of their size, such as chemical reactivity, energy absorption and biological mobility. Nanoparticles occur widely in nature and are object of study in many sciences such as chemistry, physics, geology and biology. Being at the transition between bulk materials and atomic or molecular structures, they often exhibit phenomena that are not observed at either scale. The production of nanoparticles with specific properties is an important branch of nanotechnology. Nanoscience and Nanotechnology are the two terms related with nanoparticles. Nanoscience is study of phenomenon and the manipulation of material at atomic, molecular scales. At nanoscale, materials exhibit strikingly different chemical and physical properties. It's not that new laws of nature are being exposed, but a reduction in size brings about differences in how familiar laws of physics play out at a small scale. Nanoscience is also known as the study of structures with at least one of their dimensions measuring between 1 and 100 nm. Nanotechnology is considered as an allowing technology by which existing materials, can obtain different properties making them appropriate for several novel applications. It is believed that, nanotechnology has the potential to increase the efficiency of energy consumption and increasing the manufacturing of products at reduces cost. Materials act differently with enhanced properties, when the size is reduces
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Review Paper
A Review on Nanoferrites in Biomedical Applications
Indu Sharma* and Eden Garg
Centre for Nano-Science and Technology, Career Point University-Hamirpur, India.
ARTICLE INFORMATION ABSTRACT
Introduction
In recent years, Nanotechnology has become an intense area of scientific research due to its potential applications in the field
of biology & biomedicines, optics and electronics, catalysis and many others. Nanotechnology deals with the study
nanoparticles having at least one dimension roughly between 1 to 100 nm. Nanoparticles are usually distinguished from
microparticles (1-1000μm), fine particles (sized between 100 and 2500nm), and coarse particles (ranging from 2500 to
10,000nm), because their smaller size drives very different physical or chemical properties, like colloidal properties and
optical or electrical properties. Being more subject to Brownian movement, they usually do not sediment, like colloidal
particles. Nanoparticles have a number of properties that distinguish them from bulk materials simply by virtue of their size,
such as chemical reactivity, energy absorption and biological mobility.
Nanoparticles occur widely in nature and are object of study in many sciences such as chemistry, physics, geology and
biology. Being at the transition between bulk materials and atomic or molecular structures, they often exhibit phenomena that
are not observed at either scale. The production of nanoparticles with specific properties is an important branch of
nanotechnology. Nanoscience and Nanotechnology are the two terms related with nanoparticles. Nanoscience is study of
phenomenon and the manipulation of material at atomic, molecular scales. At nanoscale, materials exhibit strikingly different
chemical and physical properties. It’s not that new laws of nature are being exp osed, but a reduction in size brings about
differences in how familiar laws of physics play out at a small scale. Nanoscience is also known as the study of structures
with at least one of their dimensions measuring between 1 and 100 nm. Nanotechnology is considered as an allowing
technology by which existing materials, can obtain different properties making them appropriate for several novel
applications.
It is believed that, nanotechnology has the potential to increase the efficiency of energy consumption and increasing the
manufacturing of products at reduces cost. Materials act differently with enhanced properties, when the size is reduces
Vol. 11. No.2. 2022
Contents available at:
http://www.crdeepjournal.org
International Journal of Basic and Applied Sciences (ISSN: 2277-1921) (CIF:3.658 ; SJIF: 6.823)
(A Peer Reviewed Quarterly Journal)
Corresponding Author:
Indu Sharma
Article history:
Revised: 25-05-2022
Accepted: 05-06-2022
Published: 07-06-2022
Key words:
nanoferrites,
superparamagnetism, toxicity,
MRI, targeted drug delivery
and magnetic hyperthermia.
Magnetic nanoferrites have shown immense potential in the biomedical applications
owing to their ability to precisely control the behavior by external magnetic field.
Superior magnetic properties of ferrites make them promising nanoagents in various
applications like targeted drug delivery magnetic separation, biosensors, MRI,
antimicrobial agents and magnetic hyperthermia (MHT).The challenge is to maintain the
high magnetization which decline when size is reduced to nanoscale, so the engineering
of these nanoferrites is of prime importance where selection of appropriate synthesis
method plays very important role. Hence the parameters like morphology, chemical and
physical properties and biocompatibility affect the efficiency of nanoferrites in
biomedical applications.
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typically from 100nm down to atomic level. As the size decreases, quantum effects begin to play a significant role, these can
change a material’s magnetic, electrical or optical properties. Most material processing techniques are based on breaking up
large chunk of materials into desired shape and size, inducing strain, lattice defects and other deformations in the processed
materials. Recent developments in nanotechnology and the demonstrations of various quantum size effects in nanoscale
particles, implies that most of the novel devices of the future will be based on properties of nanomaterials. Each nanoparticle
contains only about 3- atom/molecules. Alternative synthetic technique for nanoparticles involves controlled
precipitation of nanoparticles from precursor dissolved in a solution. The last few decades saw substantial development in the
field of nanotechnology, particularly in physical sciences. The synthesis of nano crystalline spinel ferrites plays an important
role in determining their physical properties at nano and sub nano levels. Ferrites have established their potential in several
applications due to their remarkable electrical and magnetic properties and also in magnetic resonance imaging (MRI).
Ferrites
Ferrite, a ceramic like material with magnetic properties that are useful in many types of electronic devices. These are a
unique class of compounds comprising lanthanides and fast transition metals. Ferrites are hard, brittle, iron containing and
generally gray or black and are polycrystalline. They are electrically non-conductive. They are composed of iron oxide and
one or more other metals in their chemical combination.
A ferrite is formed by the reaction of ferric oxide with any other metals including magnesium, aluminum, barium,
manganese, copper, nickel, cobalt or even iron itself.A ferrite is usually described by the formula M (Fe xOy), where M
represents any metal that form divalent bonds, such as any of the elements mentioned earlier. Ferrites belong to a group of
magnetic materials extensively used in many applications such as microwave devices, computer memory chip, magnetic
recording media, transformer cores, rod antennas and many branches of telecommunication and electronic engineering [1].
Ferrites Beads and cores are used in equipment design to suppress and dissipate high frequency noise levels caused by
electromagnetic devices.
Fig 1. Structure of ferrite)
- High resistivity
- Wide frequency range
- Low cost
- Large selection material
- Economical assembly
- Temperature and time stability
Ferrites have a paramount advantage over other types of magnetic materials: high electrical resistivity and resultant low eddy
current losses over a wide frequency range. Additional characteristics such as high permeability and time/temperature
stability have expanded the use of ferrites into quality filter circuits, high frequency transformers, wide-band transformers,
adjustable inductors, and other high-frequency electronic circuitry. As the high frequency performance of other circuit
components continues to improve, ferrites are routinely designed into magnetic circuits for both low-level and power
applications [2].
Structure of ferrite material
The crystal structure of ferrite is spinel. Ferrites are a class of spinel material that adopt a crystal motif consisting of cubic
close-packed or face centered cubic structure. They have a general formulation , where A and B are metallic
cations positioned at two different crystallographic sites, tetrahedral (A sites) and octahedral (B sites), composed of Fe as one
of the main elements in their structure. Here, A is divalent cation A2+, is occupying one eighth of the tetrahedral holes and B
is a trivalent cation B3+, is occupying half of the octahedral holes [3,4].
Spinel ferrites maybe colorless but have shades of red, green, yellow, and brown. The structure of spinel ferrites is complex,
which consist of a closed-cubic packed array of 32 oxides ions, which forms 64 tetrahedral and 32 octahedral sites in one unit
cell [containing eight formula units (M2+Fe23+O4)8]. The distribution of cations among the tetrahedral and octahedral site
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plays an important role in deciding the electrical, dielectric, magnetic and structural properties of spinel
ferrites[5,6].Depending on how cations occupy different positions, spinel structure can be of two types: Normal spinel and
Inverse spinel.
Normal Spinel: These are having chemical formula, . In this structure, all the ions
occupy the tetrahedral sites and the ions occupy the octahedral sites as shown in fig.1. E.g.: MgAl2O4.Inverse
Spinel: These Spinel having chemical formula . In this structure, ½ of the ions occupy
the tetrahedral sites and remaining ½ and all ions occupy the octahedral sites as shown in fig 2.
E.g.: .
Fig. 2. AB2O4 Spinel
Nickel ferrites
Nickel Ferrite is an important magnetic material with a variety of applications, such as fabrication of ferrofluids, catalysis,
and magnetic refrigeration and is one of the most important soft ferrites with low conductivity, low eddy current losses and
high electrochemical stability, good mechanical hardness, and chemical stability [7]. Furthermore, the bulk phase of nickel
ferrite is fully composed of inverse spinel structures. Researchers revealed that the structure and morphology (shape, size and
surface topology) of ferrite nanostructures can be controlled accurately by adjusting the composition as well as the methods
of syntheses. Over the years, diverse techniques have been developed to prepare ferrite nanostructures such as solid state, sol-
gel, thermal decomposition, co-precipitation, hydrothermal and mechanical milling. Despite many dedicated efforts, a highly
efficient and accurate method for the synthesis of ferrite nanostructures is far from being achieved. On top, the correlation
among the compositions, cationic distributions in the structure in the structure, electric and magnetic properties of ferrite
nanostructures have not been established yet. This ferrite is an inverse spinel ferrite in which eight units of NiFe2O4 go into
the cell of the spinel structure. Half of the ferric ions preferentially fill the tetrahedral sites and the others occupy the
octahedral sites. Thus, the compound can be represented by the formula (Fe3+)A [Ni2+Fe3+]BO42-.
Nickel Ferrite presents similar magnetic properties to magnetite and maghemite. The properties of synthesized materials are
influenced by the composition and microstructure, which are sensitive to the preparation methodology used in synthesis.
Additionally, the magnetic behaviors of nanoscale NiFe2O4nanoparticles are extremely sensitive to size. There is already a
significant interest in synthesizing NiFe2O4 nanoparticles for achieving optimal magnetic properties. Various methods such as
sol-gel method, organic gel-thermal decomposition method, hydrothermal method, co-precipitation method, gel assistant
hydrothermal route, thermolysis, wet chemical co precipitation technique, microemulsion and microwave synthesis have been
developed to prepare nanocrystalline nickel ferrite [8].Modern saturation magnetization and wide band gap of nickel ferrite
nanoparticles makes them appropriate for photocatalytic and waste water applications. The large tuning ability of nickel
ferrite makes it possible to implement the performances of devices used in sensing and biomedical applications as contrast
agent for magnetic resonance imaging and heat mediator for magnetic fluid hyperthermia [9]. The key application of nickel
iron oxide nanoparticles are as follow:
- Repulsive suspension for levitated railway systems
- In preparation of nickel cermet for the anode layer of solid oxide fuel cells
- High-density magnetic recording media
- Magnetic refrigeration
- As a catalyst, magnetic liquid, and microwave absorbers
- In lithium nickel iron oxide cathodes for lithium micro batteries
- In electrochromic coating, plastics and textiles
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- In nanowires, nanofibers and specific alloy and catalyst applications
Literature review
Nickel ferrite nanoparticles were synthesized using co-precipitation method. X-ray diffraction pattern was used to determine
the structure of NiFe2O4 nanoparticles. The presence of NiFe2O4 nanoparticles was confirmed by FT-IR spectrum. The details
of surface morphology of NiFe2O4 nanoparticles were obtained by Scanning Electron Microscopic analysis. The particle size
of nickel ferrites nanoparticles could be determined by means of Transmission Electron Microscopy. The work aimed at the
investigation of the dielectric properties such as the dielectric loss and the dielectric constant of nickel ferrite nanoparticles at
varied frequencies and temperatures. In addition, the magnetic properties of nickel ferrites were studied. The fact that
NiFe2O4 nanoparticles belonged to cubic spinel structure established by XRD. The average particle size of NiFe2O4
nanoparticles was found to be 28nm. From the dielectric studies it become evident that the frequency negatively impacted
both the dielectric constant and the dielectric loss decreased with increase in the frequency [10].
The NiFe2O4 nanoparticles were synthesized by the hydrothermal method and the inhibition of surfactant on the particle
growth is investigated. It showed that the products were pure NiFe2O4 and also nanoparticles grow with increasing the
temperature, while surfactant prevents the particle growth under the same condition. The average particle size was
determined by the TEM micrographs and found to be in the range of 50-60 nm that decreased up to 10-15 nm in the presence
of surfactant. Nano sized nickel ferrite particles were synthesized with or without surfactant assisted hydrothermal methods.
The result showed that with increasing in the temperature, the crystallinity of nanoparticles is increased. In the presence of
surfactants, the crystallinity of NiFe2O4 nanoparticles decreased in comparison with surfactant - free prepared samples. All of
the nickel ferrite nanoparticles were superparamagnetic at room temperature [11].
Neodymium (Nd3+) doped NiFe2O4 materials was prepared by solid state reaction. The properties of the obtained material
were investigated by X-ray diffraction (XRD), Scanning Electron Microscope (SEM), Fourier-Transform Infrared
Spectroscopy (FT-IR). The Phase analysis of the samples of NiFe2O4 doped by various content of Nd showed that they
consist of two different phases: Nd3+ doped NiFe2O4 and NdFeO3. NdFeO3 phase occurred in the sample where 5% Nd
doping was applied. From the spectra analysis, it can be concluded the Nd atoms (Nd3+ ions) substitute Ni Atoms (Ni2+ ions)
in the octahedral sites probably due to its ionic radius which is close to the limiting size of the octahedral sites. The
concentration of Nd atoms is so high that it is not possible to substitute all Ni2+ ions in the octahedral sites by Nd atoms
available in the reaction system. Thus, the excess of Nd atom favors the formation of the NdFeO3. All NiFe2O4 materials
have well defined crystals with different shapes, the new NdFeO3 phase could be identified in the SEM images as well. The
NdFeO3 phase occurrence increases with the ratio of Nd [12]. Nickel zinc nanoferrites (Ni1-x Zn x Fe2O4) was synthesized via
chemical co precipitation method having stoichiometric proportion (x) altering from 0.00 to 1.00 in steps of 0.25. The
synthesized nanoparticles were sintered at 800 degree Celsius for 12h. The experimental results demonstrate that precipitated
particles size was in the range of 20-60nm. Scanning Electron Microscopy is used to investigate the elemental configuration
and morphological characterizations of prepared samples. FTIR spectroscopy data for respective sites were examined in the
range of 300-1000cm-1[13].
Ni0.5M0.5Fe2O4nanoparticles was synthesized by using citrate precursor method. The citrate precursor was annealed at
temperature 400 degree Celsius. The annealed powders were characterized using X-ray diffractometer. Observed XRD data
was further analyzed which showed that particles annealed at temperature up to450 Degree Celsius display cubic spinel
structure while the particles formed at temperature higher that 450degree Celsius display a tetragonal spinel structure. Sharp
changes were observed in particle size, lattice constant, magnetization and retentivity in the range 450-500degree Celsius
temperature suggesting that growth s different at temperature above and below a critical temperature in this range. The
properties of nano size ferrite samples crucially depend on the synthesis temperature [14].
NiFe2O4 nanoparticles were synthesized using co-precipitation method. The X-Ray diffraction was used to determine the
structure of nickel ferrite nanoparticles. The fact that NiFe2O4nanoparticles belonged to cubic spinal structure was established
by XRD. The presence of nickel ferrite nanoparticles was confirmed by FT-IR spectrum. The details of surface morphology
of NiFe2O4 nanoparticles were obtained by scanning electron microscopic analysis. SEM analysis showed that nanoparticles
agglomerated to form spherical-shaped particles. The particle size was determined by Transmission electron microscopy. The
average particle size of NiFe2O4 nanoparticles was found to be 28 nm. The work aimed at investigation of the dielectric
properties such as dielectric loss and dielectric constant of NiFe2O4 nanoparticles at varied frequencies and temperature.
From the dielectric studies it became evident that the frequency negatively impacted both the dielectric constant and the
dielectric loss as decreased with increase in the frequency [15].
NiFe2O4was synthesized by two methods chemical sol gel method and the high frequency plasma chemical synthesis and
magnetic properties, crystalline size, specific surface area of synthesized products was characterized. The average particle
size of nano powders obtained by the sol-gel method self-combustion method is in the range of (25-40) nm and ferrites
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synthesized in plasma have wider particle size distribution range (10-100) nm with some particles of 200 nm. The magnetic
properties of sample obtained by the sol gel self-combustion method differ from those of the plasma products. Dense material
from the plasma nano powders forms at 1000 degree Celsius but from the sol gel self-combustion nano powders at
1200degree Celsius [16].
Mono-dispersed NiFe2O4 nanoparticles were synthesized using a stable ferric salt of FeCl3 with co-precipitation technique for
study of their structural, morphological and magnetic properties. The XRD confirms the FCC structure. The crystal size is
found to be ranging from 33 to 54 nm. Morphological studies have been done using AFM. The images so obtained shows that
well mono-dispersed disc shaped and uniform particles are obtained. The grain size was found to increase while thickness of
the grain decreases with increase in bath temperature. Magnetic studies on above sample were carried out by using sample
magnetometer at 80k with maximum applied of 1025Oe. It has been observed that coercivity increases with the increase in
grain size. The saturation magnetization was found to increases with the grain thickness. The resistivity measurements
suggest that the metal to semiconductor transition occurs, and decreases in T min, suggest the transition depend on particle size
[17].
Synthesis methods
Sol-gel method
Sol-gel is a method, for material preparation under mild condition, of solidifying a compound containing a highly chemically
active component through a solution, sol, or gel and then heat- treating an oxide or other compound. Sol is a colloidal system
with liquid characteristics. The disperse particles are small or macro-molecules. The particles size is between 1 and 100 nm,
and the particles are evenly distributed in the dispersion medium whereas Gel is the colloidal particles or polymers in the sol
or solution that are connected to each other under certain conditions to form a spatial network structure [18]. Sol-gel method
involves several steps in order as- hydrolysis and polycondensation, gelation, aging, drying, densification and crystallization.
It is a bottom-up approach. The Sol-gel method is to use a compound containing a high chemically active compound as a
precursor, uniformly mixed with these raw materials in the liquid phase, and perform hydrolysis and condensation chemical
reactions to form a stable transparent sol system in solution. The sol slowly polymerizes between the aged colloidal particles
to form a gel with a three- dimensional network structure. The gel is dried, sintered and solidified to prepare molecular and
even nano-substructure materials. The primary difference between a sol and a solution is that the solution is a single-phase
system, while sol is a suspension made up of small particles mixed in a solution media.
A typically sol-gel process comprises of hydrolysis and condensation of precursor materials in solution media. The
conventionally preferred precursor materials include metal alkoxides or inorganic and inorganic salts. In sol-gel method, the
size of nanoscale clusters and the morphology and microstructure of the ultimate product are tailored through controlled
hydrolysis and condensation reactions. The size of these particles is also tuned as a function of concentration of the reacting
species and aging time. Sol-gel method is a cost effective, simple and facile method. The obtained final products are
relatively homogeneous in nature with high purity. Figure 3.1.0shown below shows the outline of sol-gel process.
Fig 3. Sol-gel technique
Sol-gel synthesis parameters
There are many parameters for the sol gel synthesis processes, such as precursor selection, reaction time, reaction ratio,
solution pH, reaction temperature, drying methods etc. We will choose a few of them to illustrate.
a) Precursor selection
Generally, metal alkoxide or metal inorganic salts are selected as precursors. The metal alkoxide is easy to hydrolyze, the
technology is mature, and the reaction process can be controlled by adjusting the pH value. However, alkoxides that are
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expensive and have a large metal atomic radius have great reactivity, are easily hydrolyzed in the air, and are difficult to
produce on a large scale. The metal inorganic salts are cheap and easy to industrialized, nit it is not easy to precisely control
the reaction process. Therefore, metal inorganic salts are suitable for industrial production, and metalalkoxide are suitable for
precise research.
b) Reaction temperature
The reaction temperature has a directly relationship with the gel time and whether it is gel. Increasing the temperature can
shorten the gel time of the system and is beneficial to the hydrolysis of the alkoxide. When the temperature of the system
increases, the average kinetic energy of the molecules in the system increases, and the rate of molecular movement increases,
thus increasing the number of reactive groups. The probability of collision between the two, and can make more precursor
raw materials become activated molecules, which is equivalent to improving thehydrolysis activity of alkoxide, thereby
promoting the progress of the hydrolysis reaction, and ultimately shortening the gel time.
Solid-state method
The solid-state method is commonly used for the synthesis of the single crystal and polycrystalline powders of phosphates
and arsenates of transition metals and monovalent cations [19]. This synthesis is a common method to obtain polycrystalline
material from solid reagents. This method is used to cause a chemical reaction from solid starting materials to form a new
solid with a well-defined structure. Fine grain metal compounds are combined, pelletized, and heated at a controlled
temperature for a specific time period. Some metal compounds such as metal oxides or salts, require extreme conditions, such
as high temperature and pressure, to initiate reactions in a molten flux or a rapidly condensing vapor phase. This process is
often referred to as “shake and bake” or heat and beat” chemistry. The reaction rate in solid state synthesis is particularly
important to characterize. Solid-state reactions must go to completion, as techniques for purification of formed solids are
severely limited. The rate of the solid-state reaction depends on the reaction conditions, including the structural properties,
shape and surface areas of the reactants, the diffusion rate, and the thermodynamic properties associated with the reaction.
The chemical and physical properties of the final materials are determined by the chemical precursors and preparation
techniques. In this method, reactions of metal compounds are initiated by an energy source and propagated by the heat
released during the formations of products and byproducts.
The disadvantages of this method are that it is very slow and needs a lot of energy. In fact, the reaction occurs at high
temperatures (500-2000 degree Celsius) for several hours and for same time for several days. The heating at these
temperatures may decompose the desired compound.[19]
Hydrothermal method
Hydrothermal method is a non-conventional method to obtain nano crystalline inorganic materials. It is defined as a
homogeneous or heterogeneous reaction that takes place in the presence of aqueous solvents under high temperature and
pressure, to result with the formation of solid products that are relatively insoluble under ordinary conditions. It is a cost
effective and environment friendly technique. Temperature, water, pressure and the time of reaction are therefore the three
necessary physical parameters in hydrothermal processing. Generally, this synthesis method is also known as solvothermal
process, which means that apart from water other solvents are also used.
In a typical experiment, the precursor material is dissolved in a suitable solvent and transferred into a stainless-steel vessel
called as autoclave. Water is usually preferred as the solvent in such experiment. Once, the transfer process is completed, the
vessel is sealed tightly and subjected to thermal treatments. The temperature is fixed over 80 degree to 250 degree Celsius for
the synthesis of simple nanostructures. At these, elevated temperature the supercritical solvent reacts one the precursor
material which result in the formation of products. Surfactants are also involved in such reactions, along with the precursor
materials to procure a nanostructure with a desired morphology. In addition, the simplicity and elegance process is getting
lost [20]. Alumino phosphate nanosheets were procured by hydrothermal method [21].
Application of nanoferrites in biomedical sciences
Iron oxide nanoparticles specially ferrites have gained a lot of attention in recent years due to their applications in diverse
field and particularly in biomedical field where there enhanced magnetic properties offer diversity in imaging diagnosis and
treatment. There are numerous types of ferrites that have been synthesized and presented for different applications but ferrite
based on cobalt, nickel, and zinc has shown potential for biomedical applications due to high magnetic anisotropy and
biocompatibility [22]. With the aim of improving the response in magnetic hyperthermia treatments and other biomedical
applications, a nanoparticle system based on nickel ferrites has been investigated.
Monodispersed ferrites nanoparticles with different proportions of Ni2+ ions and sizes have been produced by an optimized
synthesis based on the thermal decomposition method and the seed-growth technique. All samples were chemically and
structurally characterized by different methods, and the magnetic behavior has been analyzed by means of field and
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temperature dependent magnetization measurements and electronic magnetic resonance. It has been proved that low
proportions of Ni2+cation in the structure favors have saturation magnetization values and a reduction of the magnetic
anisotropy constant [23].Magnetic Nanoparticles (MNPs) have recently shown great potential in biomedical applications.
MNPs can be used in drug delivery, heat generation, magnetic resonance imaging (MRI) contrast agents, protein separators,
among other applications. Because of their wide range of applications, MNPs can be used for simultaneous diagnosis and
therapy. However, the properties and characteristics of the magnetic material should be tailored to have a good performance
for both uses (diagnosis and treatment). Several reports on the use of MNPs for diagnosis as contrast agents for MRI or for
the treatment of cancer as heat generators in magnetic fluid hyperthermia are available in the scientific literature. Although
both applications are the result of magnetic fields interacting with each other [24].
In Hyperthermia
Hyperthermia, a moderate increase in temperature to 40-43 degree Celsius, can cause the death of cancer cells and enhance
the effects of radiation and chemotherapy. However, the achievement of its full potential as a clinically significant treatment
method was limited due to its inability to heat malignant cells efficiently and locally. This problem can be circumvented by
the intravenous administration of magnetic nanoparticles aimed at cancer cells that accumulate in the tumor, followed by the
use of an alternating magnetic field to increase the temperature of nanoparticles located in the tumor tissue. This targeted
approach allows locally heating cancer cells, at the same time, without damaging surrounding normal tissue, which
potentially increases the effectiveness and safety of hyperthermia. The most used materials for magnetic hyperthermia are
magnetite or maghemite nanoparticles. Magnetic nanoparticles can be delivered to the tumor via intra-tumoral, intra-arterial,
intra-cavitary, intravenous administration. There oral administration is not possible as most of the nanoparticles will be
excreted from the body. Intra-tumoral and intra-cavitary administration localizes magnetic particles in the tumor and can lead
to effective heating of primary tumors. Although the above methods of administration are well suited for specific cases,
intravenous administration is the most versatile delivery method for a wide range of oncological diseases. When magnetic
particles of iron oxide are delivered in this way, the accumulation of nanoparticles of tumor partially depends on the effect of
increase permeability and retention [25]. This effect refers to the tendency of nanoparticles to predominately accumulate in
tumors due to the permeability of their vasculature and poor lymphatic drainage. Target ligands (antibodies and their
fragments, ligands of specific receptors localized on the surface of tumor cells, peptides, and aptamers) associated with the
magnetic particles can enhance the absorption of nanoparticles by malignant cells [26]. Their predominate accumulation in
malignantneoplasms leads to targeted local heating of tumors and the preservation of neighboring normal tissues under the
influence of an alternating magnetic field.
Despite the promising results of preclinical trials of magnetic hyperthermia, there are many unsolved problems in this area.
This includes the establishment of optimal limits of magnetic field strength and frequency, their correlation with the duration
of treatment, the toxicity of, magnetic nanoparticles (including the dependence of toxicity on the presence of specific ligands
that improve the accumulation of magnetic particles in tumor cells), and determining their optimal concentration in the
affected organ.
In cancer diagnosis and MRI
As early diagnosis is associated with positive outcome, using any type of therapy, there are many incentives for developing
technologies that can detect cancer at its earliest stages [27]. In most cases, detection of stage 1 cancer is associated with a
higher that 90% 5-year survival rate [28,29] due to availability of curative treatment. Currently cancer is detected using
various medical tests such as blood, urine or imaging techniques. Conventional imaging techniques typically detect cancer
when they are few millimeters (e.g., MRI) or centimeters (e.g., PET) in diameter, at which time they already consist of more
than a million cells. Recently proposed molecular imaging aims at rectifying this disadvantage. The development of this new
imaging modality became possible due to recent progress in nanotechnology, molecular cell biology, and imaging
technologies. While molecular imaging imaging applies to various imaging techniques such as Positron Emission
Tomography (PET), computed tomography, or ultrasound, of particular interest is magnetic resonance imaging (MRI) that
provides the best spatial resolution when compared to other techniques and is noninvasive or at least minimally invasive.
Unfortunately, MRI has not been applied to its full potential for the diagnosis of cancer mostly because of its low specificity
(false-positivity rate of 10% for breast cancer. The lack of MRI specificity can be, however, rectified using cell markers and
unique properties of paramagnetic and superparamagnetic nanoparticles (NP), which can be utilized to be detected with MRI
in small quantities.
Super(paramagnetic) nanoparticles when placed in the magnetic field disturb the field disturb the field causing faster water
proton relaxation, thus enabling detection with MRI. Nanoparticles, typically smaller than 100nm, have been applied to
medicine due to their unique magnetic properties and sizes, comparable to the largest biological molecules, such as enzymes,
receptors, or antibodies, that enable diagnostic, therapy as well as combined therapy and diagnosis [30,31]. Nanoparticles
with potential MRI-related medical applications comprise various materials such as metals (gold, silver, and cobalt) or metal
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oxides (Fe3O4, TiO2, and SiO2).The most common and the first to be applied in MRI nanoparticle is the so small and
ultrasmall superparamagnetic iron oxide (SPIO and USPIO). Magnetic iron oxide particles have been used clinically since
1987, when they were applied for the detection of focal liver and spleen lesions with MRI.
Applications of iron-based nanoparticles improved MRI sensitivity due to accumulation of iron in the liver caused by
selective action of the hepatobiliary system. Nanoparticles have been recently utilized by biologists, pharmacologists,
physicists, physician as well as pharmaceutical industry. There are about 20 clinically approved nanomedicines used for the
treatment. Some examples are Abraxane, an albumin-bound form of paclitaxel with cobalt of mean particle size of
approximately 130nm that is used to treat breast cancer and Doxil, also based on Cobalt, is used for the treatment of
refractory ovarian cancer and AIDS-related Kaposi’s sarcoma and it consist of nanoparticles with a polyethylene glycol
coating. A primary attribute of nanoparticles delivery systems is their potential to enhance delivery systems is their potential
to enhance the accumulation of anticancer agents in tumor cells as some nanoparticles passively accumulate in tumors after
their intravenous administration. Nanoparticles can penetrate through small capillaries and are taken up by cells, which allow
efficient drug accumulation at target sites enabling also sustained and controlled release of drugs at target sites over a period
of days and weak [27].
In drug delivery
Because of their simplicity, efficacy, ease of preparation, and ability to adapt their properties for particular biological
applications, the use of spinel ferrites nanoparticles as a drug delivery agent under the control of am external magnetic field
has got a lot of attention [32-35]. About a century ago, German scientist Paul Ehrlich (1854-1915), proposed the concept of a
“magic bullet” that would destroy only diseased tissue [36]. In 1950s the modern history of drug delivery can work on micro-
encapsulated drug particles [37]. Since then, the number of publications in this biomedical area has increased dramatically.
Many analyses and research paper involving nanoparticles derived from silica [38-40], gold, polymers, and other materials
are currently available in literature. As a result, it’s easy to see the magnetism isn’t a necessary feature when designing a drug
delivery nano system since a wide range of nanomaterials can be used. However, in recent decades, the use of magnetic
nanoparticles in drug delivery has got a lot of attention [41]. The traditional method of drug delivery from non-specific cell
and tissue distributions with metabolic instability resulting in whole body toxicity and reduced therapeutic efficacy [42].
Another intriguing feature of spinel ferrite nano particle is their ability to encapsulate cytotoxic drugs within the polymers
matrix and deliver them to cells [43-46]. Spinel ferrite nanoparticles can hold drugs and circulate without spilling, and with
the help of an external magnetic field they can easily travel to the target tumor site and assist in delivering successful
therapeutic care of cancer cells by by-passing normal cells [47]. The medication will be released and have therapeutic effects
until it reaches the sites of action. Multifunctional Nano particles, which are made up of spinel ferrite nanoparticles, anti-
cancer drugs, semiconductors (for cell imaging), and biocompatible coating agents, are particularly valuable for cancer
therapy. It has been documented that lauric acid capped CoFe2O4 nanoparticles could be used as a promising drug delivery
agent with pH sensitive release [48]. Furthermore, capping or coating spinel ferrite nanoparticles with biocompatible
materials may help to improve their stability and reduce their toxicity in cells. To be used for magnetically driven drug
delivery, spinel ferrite nanoparticles must have no residual magnetization after the external magnetic field has been removed.
This also allows them to preserve colloidal stability and prevent aggregation, allowing them to be used in biomedical
applications [49]. Magnetic attraction between the particles is one of the predicted reasons for spinel ferrite nanoparticles
agglomeration [50].
Conclusion
In this chapter role of nanoferrite in MRI, targeted drug delivery and magnetic hyperthermia application was briefly
described. The tunable magnetic behavior and magnificent properties of nanoferrites makes them promising candidate for all
these biomedical applications. Stability and biocompatibility are the major concerns which require attention while using
various nanoferrites for biomedical applications to improve the efficacy. Although nanoferrites have been extensively studied
in vitro studies but there is still the scarcity of clinical studies of nanoferrites.
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