Chapter-1 Introduction

D. Y. Patil University, Kolhapur 1

1.1. Introduction to nanoparticles

In nanotechnology, a nanoparticle (NPs) is defined as a small object that

behaves as a whole unit in terms of its transport and properties. It can be

categorized according to their size and diameters. Mainly they are classified into

compact materials and nanodispersions. A NP is a quasi-zero-dimensional (0D)

nanoobject in which all characteristic linear dimensions are of the same order of

magnitude (not more than 100 nm) [1-3]. Nanodispersions, unlike nanostructured

materials, include a homogeneous dispersion medium (vacuum/gas, liquid, or

solid) and nanosized inclusions dispersed in this medium and isolated from each

other. The distance between the nano-objects in these dispersions can vary over

broad limits from tens of nanometers to fractions of a nanometer. Such

nanostructured systems constitute a bridge between single molecules and infinite

bulk systems. Nanomaterials can be differentiated based on the shapes as zero

dimensional (quantum dots, spherical, elliptical NPs), one dimensional

(nanowires) and two dimensional nanostructures (nanoplates, nanocubes). The

chemical and physical properties of NPs can significantly differ from those of

bulk materials of same chemical composition. The experimental and conceptual

background for the field of nanoscience is constituted by the energetics; the

uniqueness of structural characteristics, response, dynamics and chemistry of

nanostructures. The underlying themes of nanoscience and nanotechnology are

as follows: first, the bottom-up approach of the self assembly of molecular

components where each molecular or nanostructured component plugs itself into

a superstructure [2]; and second, the top-down approach of miniaturization of the

components [3]. Some of the size dependant properties of NPs are: Change in

Thermal properties – melting temperature, Electrical properties – tunneling

current, Magnetic properties – superparamagnetic effect (Ex. Iron oxide is

ferromagnetic in bulk while below 14 nm it shows superparamagnetic

properties), Optical properties – absorption and scattering of light, surface

plasmon resonance effect; Chemical properties–reactivity, catalysis (Ex. Bulk

gold is noble while nanoparticles of gold are catalysts); Mechanical properties –

adhesion, capillary forces.

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 2

The use of nanoparticles in biotechnology and medicine merges the fields

of material science, chemistry, physics and biology. Nanostructured materials,

such as NPs, nanowires, nanotubes and thin films, provide a particularly useful

platform for successful development of wide-ranging therapeutic and diagnostic

applications in the biomedical area [4]. Due to the tremendous development of

this field of research worldwide, the term “nanomedicine” was recently coined

[5], long after nanomaterials started to impact biomedical research. (The size

variation is shown in figure 1.1. In nanomedicine, nanoparticles play a vital role

depending upon their characteristics. The types of nanoparticles extensively

explored especially for biomedical applications are shown in Figure 1.2.

Figure 1.1. Sense of Nano Scale

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 3

Figure 1.2.Type of Nanoparticles for biomedical applications

1.2. Magnetic nanoparticles (MNPs)

MNPs are a class of nanoparticles that can be manipulated under the

influence of an external magnetic field. MNPs are composed of magnetic

elements, such as, cobalt, nickel, iron and their oxides. Engineered magnetic NPs

(MNPs) represent a cutting-edge tool in medicine because they can be

simultaneously functionalized and guided by a magnetic field. Magnetic NPs

have become important imaging tools for the prevalent diseases like cancer,

atherosclerosis, diabetes, and others. The unique ability of MNPs to resonantly

response to an external magnetic field has been utilized for magnetic resonance

imaging (MRI), cell tracking, bioseparation, tissue engineering, targeted gene

and drug delivery, and magnetic induction heating hyperthermia [6].

Nanoscale magnetic materials have attracted widespread interest because

of novel effects arising due to the reduction of their spatial extension. This has a

major impact on modern magnetic storage technology [7] as well as on the basic

comprehension of magnetism on the mesoscopic scale [8-9]. As first predicted

by Frenkel and Dorfman [10,11] a particle of a ferromagnetic material is

expected to consist of a single magnetic domain below a critical particle size.

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 4

The rough estimates of this critical particle sizes, have first been made by Kittel

[12]. An approximate radius of 15 nm is estimated for a spherical sample of a

common ferromagnetic material. The magnitude of magnetic moment ‘M’ of a

particle is proportional to its volume. These monodomain ferromagnetic particles

can be viewed as large magnetic units, each having a magnetic moment of about

thousands of Bohr magnetons.

Usually an ellipsoidal shape of the particles is assumed, where the

magnetic moments have the tendency to align along the longest axis, which

defines the direction of largest “shape” anisotropy energy [12]. The remarkable

new phenomena observed in nanomaterials arise from the subtle interplay

between the intrinsic properties, size distribution of the NPs, finite-size effects

and the interparticle interactions. Finite-size effects dominate the magnetic

behaviour of individual NPs, increasing their relevance as the particle size

decreases. Superparamagnetism is the most studied finite-size effect in small

particle systems, which is a finite-size effect since the particle anisotropy is

generally proportional to its volume.

The magnetic behaviour of particle at the surface differs from that

corresponding to core, because of the compositional gradients, distinct atomic

coordination, concentration, and nature of defects present in both the regions.

Therefore, whereas the core usually displays a spin arrangement similar to that of

the bulk material; a much higher magnetic disorder is present at the surface

giving rise to magnetic behaviours covering from that of a dead magnetic layer

to that of a spin glass- like. The competition between both magnetic orders—

surface and core—determines the ground state of the particle, which can be very

far from the simple assumption of a single domain with the perfect magnetic

ordering corresponding to the bulk material. And this is another important finite-

size effect that largely influences the magnetic response of the NPs [4, 13].

Challenges arise each day as these NPs find their way to emerging technologies

where a thorough understanding of their chemical stability, dispersion in

different media, particle-particle interactions, surface chemistry, and magnetic

response are fundamental for successful implementation.

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 5

1.2.1. Types of magnetic NPs

The random and competing interparticle interactions present in

concentrated nanostructured materials may strongly modify the dynamic

response of these systems. Firstly, by affecting the height of the energy barrier

which determines the relaxation time of each individual particle, and secondly,

by producing a collective state which shares most of the phenomenology

attributed to the magnetic glass behaviour. In some cases, where interparticle

interactions have some degree of coherence, the formation of long-range domain

like structures have been observed well below the percolation threshold, for

example, in textured thin films of Co-based granular alloys. These phenomena

can be controlled by varying the particle size and interparticle distance, whose

values are a consequence of the finite-size effects. Surface disorder and

roughness influence the spin dependent electron scattering at the magnetic/non-

magnetic interfaces in giant magneto resistive granular heterogeneous alloys and

magnetic multilayers. Besides, insulating granular solids, constituted by the

dispersion of ferromagnetic particles in an insulating matrix, display a wide

richness of transport phenomena related to finite-size and proximity effects, in

particular, the so-called Coulomb blockade and spin-polarized tunnelling

conduction. Based on the magnetic response, MNPs are classified as diamagnetic

(No response to external magnetic field, negative susceptibility), paramagnetic

(weak response, low positive susceptibility) and ferromagnetic (high positive

susceptibility). Depending on the size, magnetic nanoparticles even represent

special class of magnetism known as superparamagnetism (zero coercivity, zero

remenance).

1.2.2. Important properties of MNPs

Several forms of magnetism exist in nature, with superparamagnetism

(SPM) seeming to be preferred for MNPs applied to biomedical problems. SPM

occurs when particles are small enough for thermal fluctuations to cause random

flipping of magnetic moments. Randomization of the orientation of these

magnetic moments results in an average magnetization of zero in the absence of

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 6

an applied magnetic field. The characteristic time from one moment flip to the

next is called the Neel relaxation time and is approximated by Neel-Arrhenius

relation [16]:

where τ0 is the time between flip attempts and is typically in the range 10-9

to 10-

12 s depending on the material, K is the magnetic anisotropy energy, V is the

particle volume, kB is the Boltzmann constant, and T is temperature. From

equation, it is observed that the relaxation time decreases or flipping frequency

increases as the particle size decreases. The size limit required to achieve

superparamagnetism can vary with core material composition, but is typically

<30 nm for iron oxide crystals. Considering this threshold, MNPs with a core

larger than 20-30 nm typically consist of clusters of multiple smaller iron oxide

domains rather than a single large crystal. SPMNPs are ideal for in vivo use as

the presence of attractive forces between neighbouring MNPs (from permanent

or remnant magnetization) could lead to the formation large aggregates, which

are more easily cleared from the circulation and pose greater risks for vascular

embolism. Greater magnetic susceptibility and magnetic saturation are the

additional attractive properties of superparamagnetic MNPs compared to

paramagnetic materials when exposed to an external magnetic field [14-15]. This

high magnetic susceptibility is the result of reorientation of individual. High

magnetization iron oxide crystals responding to applied field are illustrated in

figure 1.3.

Because of their, interesting properties magnetic nanoparticles with

especially iron oxide based spinel ferrites became a first choice for biomedical

applications. The spinel structure and hence iron oxide based system is discussed

in detail below.

0 expB

KV

k T

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 7

Figure 1.3. Illustration of superparamagnetic NP response to applied magnetic

field. The dashed circle denotes the randomization of moments in the absence of

external Magnetic field

1.3. Introduction to spinel ferrites

The spinels are class of minerals of general formulation A2+

B23+

O42-

which crystallise in the cubic (isometric) crystal system where the oxide anions

arranged in a cubic close-packed lattice whereas the cations A and B occupying

some or all of the octahedral and tetrahedral sites in the lattice. A and B can be

di-, tri- or quadrivalent cations, including iron, magnesium, manganese, zinc,

chromium, silicon, aluminium, and titanium . Though the anion is normally

oxide, the analogous thiospinel structure includes the rest of chalcogenides. A-

and B- can also be the same metals under different charges, such as the case in

Fe3O4 (as Fe2+

Fe23+

O42-

). Usually Spinel crystallizes in the isometric system and

common crystal forms are octahedral and twinned. It has an imperfect octahedral

cleavage and a conchoidal fracture. Its specific gravity is 3.5-4. 1, its hardness is

8, and it is transparent to opaque with a vitreous to dull cluster. It may be

colourless, but is usually of various shades of colours such as red, blue,

green, yellow, brown or black.

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 8

The crystal structure of spinel was determined independently by Bragg

and Grimes [16 and 17]. The majority of spinel compounds belong to space

group Fd3m. Figure 1.4 shows the primitive tetrahedral unit cell of spinel. This

cell consists of two molecular AB2X4 units and is represented by two octants in

Figure, with atomic positions indicated in diagram. Four primitive cells, arranged

as shown in Fig, combine to form cubic unit cell of spinel. There are Z=8

formula units per cubic unit cell, each of which consists of 32 anions and 24

cations, for a total 56 atoms. The Bravais lattice of conventional unit cell is face

centered cubic (fcc); the basis consists of two components. The anionic sublattice

is arranged in a pseudo-cubic close packed (ccp) spatial arrangement, although

some spinels possesses almost ideal ccp anionic sublattice. As a consequence the

spinel lattice parameters are large, in natural MgAl2O4, a= 0.8089 nm. There are

96 interstices between the anions in the unit cell; however, in AB2X4 compounds

only 24 are occupied by cations. Out of 64 interstices that exist between anions;

8 are occupied by cations and remaining 16 cations occupy half of the 32

octahedral interstices. The tetrahedrally co-ordinated cations form a diamond

cubic sublattice with repeat units equal to lattice parameter. Description of

atomic positions in spinel is dependent on the choice of setting of origin in Fd3m

space group. Normal spinel structures are usually cubic closed-packed (ccp)

oxides with one octahedral and two tetrahedral sites per oxide. Tetrahedral points

are smaller than the octahedral points. B3+

ions occupy the octahedral holes due

to the charge factor, but only can occupy half of the octahedral holes. A2+

ions

occupy 1/8 of the tetrahedral holes. If the ions are similar in size; this maximises

the lattice energy. A common example of a normal spinel is MgAl2O4.

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 9

Fig 1.4. Primitive tetragonal and conventional cubic unit cells of spinel. The

primitive cell consists of two octants of the cubic unit cell. Atom positions are

shown for the primitive cell only; however the atomic positions denoted in the

primitive cell repeat with the pattern indicated by shading in the other octants.

One A-site in the primitive cell is not visible in the drawing; it is on the center of

the base of the cubic unit cell. The lattice parameter range (a=0.8-0.9nm) is

approximately the range corresponding to oxide spinels

Inverse spinel structures however are slightly different where one must

take into account the crystal field stabilization energies (CFSE) of the transition

metals present. Some of the ions may have a distinct preference on the octahedral

site which is dependent on the d-electron count. If the A2+

ions have a strong

preference to the octahedral site then they will force their way into it and

displace half of the B3+

ions from the octahedral sites to the tetrahedral sites. If

the B3+

ions have a low or zero octahedral site stabilization energy (OSSE), then

they have no preference and will adopt the tetrahedral site. The example of an

inverse spinel is Fe3O4, if the Fe2+

(A2+

) ions are d6 high-spin and the Fe

3+ (B

3+)

ions are d5 high-spin.

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 10

1.3.1. Ferrite nanoparticles

Ceramic-like ferromagnetic materials, which are mainly composed of

ferric oxide, a-Fe2O3, are called “ferrites”. As the saturation magnetization of

ferrites is less than half that of ferromagnetic alloys, they have several

advantages as applicability at higher corrosion resistance, greater heat resistance,

lower price and higher frequency. Several practical applications of ferrites have

been expanded by completely utilizing these advantages.

Magnetite, (Fe3O4) which is a natural mineral, a genuine ferrite, and it is

said that ancient people had recognized its magnetism and that it was used as a

mariner’s compass in China more than two millennia ago. The first attempt to

prepare various types of ferrites and to industrialize ferrites was not made until

the beginning of this century. Rapidly development of radio, television, carrier

telephony, and computer circuitry and microwave devices arouse attention of

people to the importance of these ferrite materials. Since then the science

evidenced the tremendous advancement in the field of manufacturing and

processing of ferrite materials.

Crystal structure of ferrite

The crystal structure of a ferrite can be regarded as an interlocking

network of positively-charged metal ions (Fe3+

, M2+

) and negatively charged

divalent oxygen ions (O2-

). [8,9]

Like to the mineral spinel, magnetic spinels have the general formula

MOFe2O3 or MFe2O4 where M is the divalent metal ion. The trivalent Al is

usually replaced by Fe3+

or by Fe3+

in combination with other trivalent ions.

Although the majority of ferrites contain iron oxide as the name might imply

there are some "ferrites" based on Cr, Mn, and other elements. Although Mn and

Cr are not ferromagnetic elements, in combination with other elements such as

oxygen and different metal ions, they can behave as magnetic ions. Thus,

chromites and manganites are possible but not important commercially. In the

magnetic spinels, the divalent M2+

can be replaced by Mn2+

, Ni2+

, Cu2+

, Co2+

,

Fe2+

, Li2+

, Zn2+

, Mg2+

or more often, combinations of these. The presence of

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 11

Fe3+

, Fe2+

, Ni2+

, Co2+

and Mn2+

can be used to provide the unpaired electron

spins and therefore part of the magnetic moment of a spinel. Other divalent ions

such as Mg2+

or Zn2+

(or monovalent Li) are not paramagnetic but are used to

disproportionate the Fe3+

ions on the crystal lattice sites to provide or increase

the magnetic moment.

1.3.2. MgFe2O4

Magnesium ferrite, MgO.Fe2O3 or MgFe2O4, can be made partially

normal at high temperatures and this normal structure can also be quenched in a

manner similar to copper ferrite. Slow cooling gives inverse structure and rapid

cooling gives normal structure. When M in the chemical formula of spinel ferrite

is a metal carrying no magnetic moment such as Mg2+

, the magnetic couplings

purely originate from the magnetic moment of Fe cations and may be relatively

weaker. Magnetic anisotropy in MgFe2O4 is lower than that of other spinel

ferrites in which all the metal cations have large magnetic moments.

MgFe2O4 is used as a catalyst in dehydrogenation of butene, humidity

sensor and recently is more applicable in achieving local hyperthermia when

compared with other ferrites. MgFe2O4 nanoparticles exhibit high resistivity~107

Ohm (low conductivity). Therefore it is the material of choice for microwave

applications, and yolk cables. Recently the use of magnetic nanoparticles in

cancer therapy emerges as a one of the important cancer modality either alone or

in combination with existing modalities. As the heat loss by magnetic

nanoparticle governed by relaxation losses, eddy current losses and hysteresis

losses, it is difficult to differentiate one loss from another. One of the approaches

is to use magnetic nanoparticles with high electrical resistivity. Eddy currents are

negligible in case of high electrical resistivity. Also the heat loss is slow in case

of high resistive material as compared conductive particles. Therefore ferrite

nanoparticles with resistivity over ~107 Ohm are preferred for magnetic

hyperthermia over other metal nanoparticles to avoid excess heating due to eddy

current losses.

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 12

Some important properties of MgFe2O4 are given in Table 1.1 [20-22].

Numerous methods have been discussed in literature for the synthesis of

MgFe2O4 magnetic nanoparticles. MgFe2O4 NPs were preferred as a potential

heating agent in magnetic particle hyperthermia. The key challenge is to produce

quantity and quality MgFe2O4 NPs with required properties such as high

chemical stability, high crystallinity, high saturation magnetization and with

good colloidal stability with or without surfactant/polymer in water. Because of

its low anisotropy and high resistivity MgFe2O4 nanoparticles are important

materials in technological applications. The magnetic properties of MgFe2O4 NPs

can be tuned by substitution of divalent metal cations (Mn2+

or Zn2+

).

Chemical formula MgFe2O4 or MgO.Fe2O3

Lattice constant ~ 8.36 Å

Oxygen parameter ~ 0.381±0.001

Density ~ 4.52 g/cm3

Magnetic moment 0 μB (Theor.) and ~1.1 μB (Expt.)

Curie temperature ~ 440 °C

Crystal anisotropy (at 20 °C) ~ ˗ 25 x 103 erg/cm

3

Linear magnetization magneto striction ~ - 6x 106

(20 °C)

Resistivity ~ 107 ohm

Tetrahedral radius 0.58 Å

Octahedral radius 0.78 Å

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 13

1.4. Literature survey

The use of magnetic NPs for magnetic induction heating in magnetic

particle hyperthermia has gained lot of attention since last decade. Though the

use of magnetic NPs for hyperthermia was not new, the appliances to medical

field were forbidden due to improper instrumentation, inexact thermotherapy and

lack of core knowledge. Synthesis of monodispersed, highly water dispersible

single domain (ferri- or superpara-) magnetic NPs is the prime challenge to the

researchers in this field. Similarly, heating due to magnetic losses depend on

sample composition and field parameters. In the present section, the synthesis

and major biomedical applications of MFe2O4 NPs have been reviewed.

Chen et al have shown that the co-precipitated MgFe2O4 nanoparticles

exhibit superparamagnetic properties for particle sizes 6 and 12 nm. They also

anticipated that the nanoparticles of MgFe2O4 may possess superparamagnetic

properties even at relatively large sizes [22]. Though the MgFe2O4 nanoparticles

have proven to be a technological important material, its potentiality in

biomedical applications was not fully explored.

Spinel ferrite, MFe2O4 (M = Co, Fe, Cd, Zn, Mn, or Mg) is a particularly

important magnetic material system [23, 24]. These NPs may possess novel

magnetic properties, particularly superparamagnetic behavior. At

superparamagnetic state; the collective behavior of the magnetic NPs is the same

as that of paramagnetic atoms. Each particle behaves like a paramagnetic atom

but with a giant magnetic moment. There is a well-defined magnetic order within

each NP. Furthermore, spinel ferrite NPs provide great experimental systems in

which one can study the correlation between the crystal chemistry and

superparamagnetic properties of magnetic NPs. When M in the chemical formula

of spinel ferrite is a metal carrying no magnetic moment such as Mg2+,

the

magnetic couplings purely originate from the magnetic moment of Fe cations

and may be relatively weaker. Magnetic anisotropy in MgFe2O4 could be lower

than that of other spinel ferrites in which all the metal cations have large

magnetic moments. Therefore, it is logical to anticipate that the NPs of MgFe2O4

may possess superparamagnetic properties even at relatively large sizes [25].

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 14

Heat generation ability of nano-MgFe2O4 based ferrite in AC magnetic

field is studied by Hirazawa et al [26]. They prepared NPs by bead milling. The

highest heat ability (ΔT=34°C) in the AC magnetic field (370 kHz,1.77kA/m)

was obtained for fine MgFe2O4 powder having about 6 nm crystal size (the

samples were milled for 6 to 8 h using 0.1 mm beads).

Giri et al [27] have explored the potentiality of different ferrite NP

(MnFe2O4 system) for hyperthermia therapy applications. The specific

absorption rate (SAR) was measured by calorimetric measurement at a frequency

of 300 kHz and a field of 10–45 kA/m. The variation of SAR and magnetization

of Fe1−xMnxFe2O4 with Mn concentration was studied and suggested that the

biocompatibility and higher SAR may make these materials useful for

hyperthermia applications. Wetzel et al [28] investigated the induction heating

behavior of NiFe2O4 soft ferrites in AC field with 5.85 MHz and 50–500 Oe.

Franco et al [29] prepared MgFe2O4 nanoparticles by combustion method and

studied their magnetic properties with respect to varying temperature. The results

were promising as compared to conventional methods to prepare MgFe2O4NPs

and combustion method was proposed to be quick and efficient method to

synthesized industrial scale MgFe2O4 NPs with enhanced magnetic properties.

Kim et al [30] have investigated various ferrite (Fe-, Li-, Ni/Zn/Cu-, Co-,

Co/Ni, Ba- and Sr-ferrites) NPs for their application in magnetic particle

hyperthermia. Temperature variation under an alternating magnetic field was

observed. Their results shown that Co-ferrite exhibited the most applicable

temperature change ΔT =19.25K (29.62 W/g), in distilled water when the field

was 110 A/m. The synthesis method was coprecipitation and sol gel. The applied

frequency was above 7 MHz.

Bae et al [31] studied cytotoxicity, AC magnetic field induced heating and

bio-related physical properties of two kinds of spinel ferrite NPs. Soft (NiFe2O4)

and hard (CoFe2O4) with variable mean particle sizes were investigated to

confirm their effectiveness as an in vivo magnetic NP hyperthermia agent in

biomedicine. Magnetically induced heating temperature of the NPs measured

both in a solid and an agar state at different applied magnetic fields and

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 15

frequencies clarified that the maximum heating temperature of NiFe2O4 NPs is

much higher than that of CoFe2O4 NPs. In particular, the sufficiently high

heating temperature of the solid-state NiFe2O4 NPs readily controlled in the

range of 21.5°C–45°C at the physiologically tolerable and biological safe range

of the applied magnetic field and frequency below 50 kHz allowed that NiFe2O4

NPs can be considered as a promising candidate for an in vivo hyperthermia

agent.

Lee et al [32] studied the self-heating temperature rising characteristics of

CoFe2O4 hard spinel ferrite NPs and compared to those of soft spinel ferrite in

order to explore the effects of magnetic anisotropy and magnetic susceptibility

on the behavior of self heating temperature rising characteristics for

hyperthermia application. The maximum temperature elevated by using specially

designed RF-MRI modified LC circuit in a solid state, was 4.6 °C. The extremely

low elevated temperature and small specific absorption rate (SAR) relevant to

the gentle slope from the time vs temperature rising curve were found to be

primarily due to a stronger anisotropy (or a smaller magnetic susceptibility) of

CoFe2O4 hard spinel ferrite NPs compared to the soft spinel ferrite NPs. They

conclude that the CoFe2O4 NPs with 165 nm in size are not suitable for

hyperthermia therapy applications.

Maehara et al [33] and Nomura et al [34] have studied selective ferrite

nanoparticles for thermal coagulation therapy. They found that magnesium

ferrite (MgFe2O4) showed the largest increase in temperature (ΔT) under an

alternating magnetic field in all the ferrites examined. For all the samples they

found, ΔT value under alternating magnetic field was increased with an increase

in frequency (200 to 500 kHz). The heating ability for the Magnesium ferrite was

1.4 W/g under AC magnetic field of 4.0 kA/m (200 W, 370 kHz). The heating

ability in alternating magnetic field was clearly depended on the magnitude of

the hysteresis loss for the ferrite powder. They showed that Mg-ferrite can

replace the usual powder “magnetite” although it should be carefully investigated

to establish the safety for putting and keeping them in a human body.

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 16

Jeun et al [35] have studied the effect of particle-particle interaction on

self heating temperature rise properties of the selective ferrites viz. NiFe2O4,

MgFe2O4 and CoFe2O4. The study depicts that the interparticle interactions play

vital role in determining the magnetic properties of MNPs when the distribution

of MNPs is broad. The superior properties of induction heating were obtained in

case of MgFe2O4 NPs compared to other spinel ferrites. The increase in

“magnetic hysteresis loss” that resulted from the particle dipole interaction was

the main physical reason for the significant improvement of ac heating

characteristics. The heating due to magnetic NPs is also strongly affected by

particle size distribution. The study of effect of particle size distribution on

heating characteristics of selective ferrite NPs is systematically presented. All the

experimental results in their work clearly demonstrate that the particle dipole

interaction formed among the NPs should be considered as one of the most

crucial physical parameters in optimizing the magnetic and ac magnetically

induced heating characteristics of NPs for a hyperthermia agent application. The

study further shows that the heat generation and SAR value for MgFe2O4 NPs is

high as compared to other ferrites CoFe2O4 and NiFe2O4.

1.5. Statement of problem

The merging of biotechnology with materials science will allow us to

apply today’s advanced materials and physiochemical techniques to solve

biological problems. Though there is tremendous advancement in the field of

medicine in recent years cancer still remains as a leading cause of death in the

world. Improper diagnosis and detection at early stages are the some of the

reasons behind it. Also the treatment now followed for treating cancer including

radiation therapy, immunotherapy, chemotherapy are comprised of side effects

such as hair loss, eye irritation etc. Thus to diagnose the cancer at the early stage

and to cure it without much side effects remains a challenge to scientific

community. The new tool, magnetic NPs are playing vital role in diagnosis and

therapy of cancer. The magnetic hyperthermia therapy in which the magnetic

NPs used to heat specific organ or whole body (depending upon the tumor) has

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 17

emerged as one the promising cancer modality either alone or in combination

with other existing cancer modalities.

The main emphasis of the present work is to develop tailored magnetic

material at the nanoscale for advanced bio-application such as magnetic particle

hyperthermia (MPH) for treatment of cancer. With this aim an attempt has been

made to prepare the magnesium ferrite NPs with suitable heating characteristics

in AC magnetic field for their use as potential heating mediators in MPH

therapy. The promising combustion method was used to synthesize the

nanoferrites with desirable characteristics. The present work is subjected to five

objectives as follows:

1. To study the effect of preparative parameters on to the microstructural and

magnetic properties of MgFe2O4 NPs synthesized by combustion method

2. To study the effect of divalent magnetic manganese substitution on the

structural and magnetic properties of MgFe2O4 NPs

3. To study the effect of dextran coating on magnetic and suspension

stability properties of MgFe2O4 NPs

4. To study the magnetic induction heating properties of MgFe2O4,

manganese substituted MgFe2O4 and dextran coated MgFe2O4 NPs

synthesized by combustion method

5. To study the biocompatible properties and to study the effectiveness of

NPs for hyperthermia therapy applications

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 18

References:

[1] V. Shubayev, T. Pisanic, S. Jin, Adv. Drug Deliv. Rev. 61 (2009) 467.

[2] E. Duguet, E Duguet, S Vasseur, S Mornet, JM Devoisselle, Nanomed.

1(2006) 157.

[3] A. Nel, T. Xia, L. Madler, N. Li, Science 311 (2006) 622.

[4] E. C. Stoner, E. P. Wohlfarth, IEEE Trans. Mag. 27(1947) 3475.

[5] X. Gao, Y. Cui, R. M. Levenson, L. W. K. Ching, S. Nie, Nat. Biotechnol.

22 (2004) 969.

[6] G. M. Whitesides, Nat. Biotechnol. 21 (2003) 1161.

[7] (a) G. A. Prinz and J. H. Hathaway, Phys. Today 48 (1995) 24.

(b) P. Grünberg, Phys. Today 54 (2001) 31.

[8] G. A. Prinz, Science 282 (1998)1660.

[9] J. L. Dormann, D. Fiorani, and E. Tronc, Adv. Chem. Phys. 98 (1997) 283.

[10] F. J. Himpsel, J. E. Ortega, G. J. Mankey, and R. F. Willis, Adv. Phys 47

(1998) 511.

[11] J. Frenkel and J. Dorfman, Nature 126 (1930) 274.

[12] C. Kittel, Phys. Rev. 70 (1946) 965.

[13] J. L. Corchero and A. Villaverde, Trends in Biotechnology.27 (2009) 468.

[14] C. D. Walkey, J. B. Olsen, H. Guo, A. Emili, W. Chan, J. Am. Chem.

Soc., 134 (2012) 2139.

[15] A. Zelenkova, J. Kováč, and V. Zeleňák, J. Appl. Phys. 108 (2010) 034323.

[16] N. W. Grimes, Phys. Technol. 6 (1975) 22..

[17] W. H. Bragg, “The structure of spinel group of crystals”, Philos. Magn. 30

(1915) 305.

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 19

[18] M. Sugimoto, J. Am. Ceram. Soc., 82 (1999) 269.

[19] J. R. Oleson, IEEE Trans. Biomedical Engg. 31 (1984) 1.

[20] A. Goldman, Modern ferrite technology, 2nd

edition, Springer, 2006

[21] J. Smit, H. Wijn, Ferrites, Philips technical library, 1959.

[22] Q. Chen, A. Rondinone, B.. Chakoumakos, Z. Zhang, J. Magn. Magn.

Mater. 194 (1999) 1-7.

[23] D. G. Fink, D. Christiansen, Electronics engineers' handbook, McGraw-

Hill, 1989.

[24] F. Fiorillo, Measurement and characterisation of magnetic materials,

Elsevier Academic Press, 2004.

[25] G Bertotti, Hysteresis in Magnetism, London: Academic Press. 1998

[26] H. Hirazawa, H. Aono, T. Naohara, T. Maehara, M. Sato, Y. Watanabe, J.

Magn. Magn. Mater. 323 (2011) 675.

[27] J. Giri, P. Pradhan, T. Sriharsha and D. Bahadurar, J. Appl. Phys. 97

(2005) 10Q916.

[28] E. D. Wetzel, B. K. Fink, Y. F. Li, and J. Q. Xiao, Army Sci. Conference,

Baltimore, MD (2000).

[29] A. Franco, Jr., T. E. P. Alves, E. C. D. Lima, E. S. Nunes, and V. Zapf,

Appl. Phys. A 94 (2009) 131.

[30] D. Kim, S. Lee, K. Kim, I. Shim, Y. Lee, J. Magn. Magn. Mater. 293

(2005) 320.

[31] S. Bae, S.Lee, A. Hirukawa, Y. Takemura, Y. Haeng Jo, and S. G. Lee,

IEEE Trans. Nanotechnology, 8 (2009)1.

Chapter-1 Introduction

D. Y. Patil University, Kolhapur 20

[32] S. Lee, S. Bae, Y. Takemura, I. Shim, T. Kim, J. Kim, H. Lee, S. Zurn, C.

Kim, J. Magn. Magn. Mater. 310 (2007) 2868.

[33] T. Maehara, K. Konishi, T. Kamimori, H. Aono, H. Hirazawa, T. Naohara,

S. Nomura, H. Kikkawa, Y. Watanabe, K. Kawachi, J. Mater. Sci. 40

(2005) 135.

[34] S. Nomura, S. Mukasa, T. Miyoshi, N. Okabe, T. Maehara, H. Aono H.

Kikkawa, K. Satou, S. Yumi, Y. Watanabe , J. Mater. Sci. 41 (2006) 2989.

[35] M. Jeun, S. Bae, A. Tomitaka, Y. Takemura, K.H. Park, S. H. Paek, K. W.

Chung, Appl. Phys. Lett. 95 (2009) 082501.