Magnetic Hyperthermia and its Applications in Cancer and
Malignant Tumors
Cindy Tatiana Rodríguez Marín, crodriguezm16@ucentral.edu.co
Electronic Engineering, Central University
Resumen — La Hipertermia Magnética es el uso del campo de
temperatura controlada dentro de tejidos dañinos, como el cáncer y
tumores malignos, actuando como elevador de temperatura a las
células dañinas por medio de nanopartículas magnéticas (MNP). Estas
nanopartículas son utilizadas entre el tamaño de los 10nm y 100nm
para que no llegue a presentarse daños en tejidos sanos en el cuerpo
humano y los rangos de temperatura donde se logra eliminar el cáncer
y tumores esta entre 42°C y 47°C, es por esto que existen diversos
componentes químicos que pueden ser utilizados para la eliminación
de las células cancerígenas tales como ferritas de zinc-calcio
(𝑍𝑛0.50 𝐶𝑎0.50 𝐹𝑒2 𝑂4 𝑦 𝑍𝑛0.25 𝐶𝑎0.75 𝐹𝑒2 𝑂4 ), sistema de partículas
(magnetita y maghemita) y el método de Hipertermia Magnética de
fluidos (MFH).
Palabras Claves: Hipertermia Magnética, Nanopartículas
Magnéticas (NMP), Cáncer, Tumores Malignos, Hipertermia
Magnética de Fluidos (MFH).
Abstract — Magnetic Hyperthermia is the use of controlled
temperature field within harmful tissues, such as cancer and malignant
tumors, acting as a temperature riser to the harmful cells by means of
magnetic nanoparticles, these nanoparticles are used between the size
of 10nm and 100nm so that there is no damage to healthy tissues in the
human body and the temperature ranges where cancer and tumors are
eliminated is between 42 ° C and 47 ° C, that is why there are several
chemical components that can be used to the elimination of cancer
cells such as zinc-calcium ferrites
(𝑍𝑛0.50 𝐶𝑎0.50 𝐹𝑒2 𝑂4 𝑎𝑛𝑑 𝑍𝑛0.25 𝐶𝑎0.75 𝐹𝑒2 𝑂4 ), (magnetite and
maghemite) particle system and the Magnetic Fluid Hyperthermia
method.
Key Words: Magnetic Hyperthermia, Magnetic Nanoparticles
(NMP), Cancer, Malignant Tumors, Magnetic Fluid Hyperthermia
(MFH).
I. INTRODUCCIÓN
Cancer is the second disease with the highest mortality rates
and from it more than derived 100 different types, according to
the World Health Organization (WHO), only in America there
are approximately 3 million new cases registered annually.
Therefore, alternative treatments are sought that can help fight
this disease. The development of new materials has kept to an
improvement in existing treatments, an example, it's the
treatment of hyperthermia, that, initially, was to raise the
temperature of the whole body between 42 and 47 ° C to
eliminate cancer and this happened at the end of 1800 [1]. In
Magnetic Hyperthermia, Magnetic Nanoparticles (MNPs)
convert their magnetic energy in thermal energy when a
variable external magnetic field is applied over time. In
controlled combustion processes of malignant tissues, the
dosage that is supplied is strongly influenced as long as the
particles are distributed inside the volume of the tumor. The
optimization of the therapeutic temperature field begins with
the control of the distribution of MNPs inside the body tissues
[2].
The importance of Magnetic Fluid Hyperthermia (MFH) will
also be known, this being one of the most promising approaches
for the innovative treatment against cancer and malignant
tumors. Its operation is basically to accumulate biocompatible
magnetic nanoparticles (MNPs) in tumor site by magnetic
orientation, and expose them to an Alternating Magnetic Field
(AMF) to generate heat inside the tumor, in the aforementioned
temperature ranges, where death is induced harmful cells [3].
In this article, different types of materials and methods of
magnetic hyperthermia will be known and how they have
evolved into positive answer for the possible solution of cancer
and tumors that happen in humans, through experimentation
and mathematical methods, further to the physical and chemical
properties of some elements that include the components that
throughout this article will be mention in more detail.
II. MATERIALS AND METHODS
A. Magnetic hyperthermia based on zinc-calcium ferrites
The application of Magnetic Hyperthermia based on zinc-
calcium ferrites, the chemical reagents that were used were:
𝑍𝑛(𝑁𝑂3 )2 . 6𝐻2 𝑂 (98%), 𝐶𝑎(𝑁𝑂3 )2 .4𝐻2 𝑂 (99%),
𝐹𝑒(𝑁𝑂3 )2 .9𝐻2 𝑂 (99.99%) y ethylene glycol (𝐶2 𝐻6 𝑂2 , 99%).
Stoichiometric quantities of which appropriate chemical
reagents were mixed with ethylene glycol ( 𝐶2 𝐻6 𝑂2 ) under
magnetic stirring for 2 hours at 40 ° C, the temperature was then
raised to 80 ° C until a dark brown shade gel was obtained. The
gel was aged for 2 hours and then dried in a heating oven for 72
hours at 95 ° C. Finally, the precursor gel was subjected to a
thermal treatment at 400 ° C for 30 minutes, with the aim of
obtaining the proposed mixed ferrites. The materials obtained
were analyzed by X-Ray Diffraction (XRD, Philips 3040),
vibrating sample magnetometry at room temperature (MMV,
Princeton Measurements Corporation, MicroMagTM 2900),
Scanning Electron Microscopy (SEM, JSM 6300, Jeol), Energy
Dispersive Spectroscopy (EDS) and Transmission Electron
Microscopy (TEM, FEI Titan 80-300) [1].
The main objective of this research is to validate that the
nanoparticles are able to raise their temperature by means of an
oscillating magnetic field, where a magnetic state induction
equipment operated at 0.2 kA / m and a frequency of 362 kHz
was used to evaluate its heating capacity.
B. Magnetic Hyperthermia based on Magnetic Nanoparticles
(MNPs).
The control of Magnetic Nanoparticles (MNPs) by means of a
magnetic field is where an important step of magnetic
hyperthermia is evidenced, but here it is important the size of
the nanoparticles for the conversion of magnetic energy to the
thermal energy that is transferred to malignant tissues. The
optimization of this parameter it can be done using a
temperature analytical model that accurately predicts the
temperature values within the tissues. The temperature field
was calculated for a geometric configuration composed of the
spherical tumoral structure surrounded by a healthy tissue,
Therefore a lognormal distribution was defined by the
following distribution function [2], as look in equation 1:
2 (𝐹𝑒3 𝑂4 ) MNP coated with lauric (dodecanoic) acid (LA) were
1 [𝑙𝑛(𝑅⁄𝑅 )] ∝ synthesized by co-precipitation and the resulting ferrofluid was
𝑔[𝑅] = 𝑒𝑥𝑝 [− 0
] 𝑎𝑛𝑑 ∫0 𝑔[𝑅]𝑑𝑅 = 1
𝜎𝑅√2𝜋 2𝜎 2
Where, R is the radius of the particle, ln [𝑅0 ] is the median and
σ is the standard deviation of R, as seen in Figure 1
Figure 1. The geometric configuration of a tumor structure surrounded by the healthy
tissue.
The heat transport in the living tissues involves the thermal
conduction, convection, perfusion of blood (delivery of the
arterial blood to the capillaries in tissues) and metabolic heat
generation. The space-time temperature distribution within
malignant and healthy tissues is described by the solution:
Ti=Ti(x,y,z,t),(i=1,2) of the bioheat transfer equation in the
living tissues [2], as look in equation 2:
𝜕𝑇𝑖
𝑝𝑖 𝑐𝑖 𝑖
= ∇[𝑘𝑖 ∇𝑇𝑖 ] + 𝑝𝑏 𝑤𝑏 𝑐𝑏 [𝑇𝑎𝑟𝑡 − 𝑇𝑖 ] + 𝑄𝑚𝑒𝑡 + 𝑃̅(𝑟) (2)
𝜕𝑡
As result of the spatial distribution of the particles after their
injection within tumor, the total volumetric heating rate has a
radial dependence in the tissues. The equation (2) can be written
using the spherical symmetry and the radial variable r as [2], as
look in equation 3:
𝑘𝑖 𝜕 𝜕𝑇𝑖 𝜕𝑇𝑖
[𝑟 2 ] + 𝑀𝑖 [𝑇] = 𝑝𝑖 𝑐𝑖 (3)
𝑟 2 𝜕𝑟 𝜕𝑟 𝜕𝑡
Based on this mathematical model, the length of the
nanoparticles are those that define the distance of the insertion
site where they are diffused, therefore, it plays an essential role
in the analysis of the temperature field, where the hyperthermic
temperature range can controlled by a proper choice.
C. Magnetic Fluids Hyperthermia (MFH)
Chemical reagents that were used were Iron-oxide magnetite
(1)
centrifuged twice and only the supernatant was retrieved to
remove large aggregates of MNP and ensure monodispersity.
By adding sodium chloride (NaCl) to the ferrofluid, the ionic
strength of the solution was increased leading to a decreased
solubility for LA. This process resulted in crystallization and
precipitation of LA and, in this way, a partial LA removal from
the MNP surface was caused inducing MNP agglomeration.
Four different samples were prepared by adding NaCl dissolved
in 𝐷𝐼 − 𝐻2 𝑂 with concentrations of 0 M, 0.1 M, 0.25 M and 0.5
M NaCl to the ferrofluid. Reference samples for each NaCl
concentration containing no MNP were prepared as well. [3].
MNP samples were investigated via transmission electron
microscopy (TEM) at 60 kV using a Zeiss LEO 906 device
(Carl Zeiss GmbH, Oberkochen, Germany). Each sample was
diluted to 300 μg (Fe)/mL and vortexed after one hour rest.
Then, 1 μL sample was pipetted carefully on 3 mm diameter
Cu/Rh-150 maxtaform-grids and dried under ambient
conditions for one hour. Three different iron concentrations of
(150, 225, 300) μg (Fe)/mL were measured. The lowest
concentration corresponds approx. to the iron concentration in
the whole extracellular space after an injection of 42 ml
Resovist to the human body. Each sample was prepared and
measured in triplicate, from which an average SLP value was
calculated. [3].
 III. RESULTS
A. Magnetic hyperthermia based on zinc-calcium ferrites

In Figure 3, the obtained results of the diffraction patterns of

the ferrites 𝑍𝑛0.50 𝐶𝑎0.50 𝐹𝑒2 𝑂4 (ID: ZCF050-400) and
𝑍𝑛0.25 𝐶𝑎0.75 𝐹𝑒2 𝑂4 (ID: ZCF075-400) are presented; this
figure also contains the diffraction patterns of ferrites 𝑍𝑛𝐹𝑒2 𝑂4
(JCPDS 22-1012) and 𝐶𝑎𝐹𝑒2 𝑂4 (JCPDS32-0168). The dotted
lines in black correspond to the zinc ferrite, and the dotted lines
in gray, to the calcium ferrite [1].

Figure 3. Diffraction patterns of ferrites ZCF050-400 and ZCF075-400.

The TEM images of the ferrites ZCF050-400 and ZCF075-400

are presented, with their respective diffraction patterns, as
shown in Figure 4. It can then be seen that the MNPs have an
irregular morphology, and that they are agglomerated due to its
high magnetization since the material is polycrystalline. It is
also possible to show that ferrite has a mostly spherical
morphology, and as in Figure 4a, the diffraction pattern
obtained indicates that the material is polycrystalline and the
average particle size was 12 nm [1], as can be seen in Figure
4b.

Figure 2. TEM images of either pure lauric acid (left row) or lauric acid coated MNP
(right row) dispersed in solutions with increasing NaCl concentrations: A,B: no NaCl;
C,D: 0.1 M NaCl; E,F: 0.25 M NaCl. G,H: 0.5 M NaCl. Images E to H show lauric acid
as gray filaments.

The main objective of this research method is to observe the

behavior of the MNP agglomeration of iron dioxide under
controlled conditions in its heating properties, which was
achieved by applying the aforementioned experimental method
and validating how it affects the heating in cellular Figura 4. Imágenes de MET (a) ferrita ZCF050-400 y (b) ferrita ZFC075-
400.
environments.
The results obtained from the Magnetic Hyperthermia tests
where this analysis turns out to be of great importance, because
it is expected that the nanoparticles have the capacity to
generate heating when subjected to an oscillating magnetic
field. For this analysis, five suspensions were used: 12, 14, 16,
18 and 20 mg in 2 ml of deionized water, with a test duration of
15 min. It is important to mention that the concentrations used
in this analysis are within the allowed range for in vitro
applications, this according to the literature [1].
B. Magnetic Hyperthermia based on Magnetic Nanoparticles
(MNPs).
The evolution of the temperature field with exponential
distribution of the particles was analyzed. The temperature
within malignant and healthy tissue was computed using the
solution of the bioheat transport equation. The following
values of the magnetic field parameters were used in the
simulations: frequency: 100 - 650 kHz and the magnetic field
amplitude: 5 - 16 kA/m. The spatial distributions of the particles
were analyzed for the values of the diffusion length - the
parameter 𝑟0 - in the range 1 ÷ 8 mm. as can be seen in Figure
5.
Figure 5. The radial distribution of the volume fraction of the particles.
The maximum value of the temperature corresponding to a
specific value of the particle diameter 𝑑𝑝 , varies with the
frequency of the applied magnetic field for both materials. For
example, at the frequency of the magnetic field: f = 100 kHz,
the maximum value of temperature corresponds to the specific
value of the mean particle diameter of 25 nm for maghemite
and 20 nm for the magnetite systems. In addition, the maximum
temperature decreases with the increase of the standard
deviation of the particle size distribution. [2].
C. Magnetic Fluids Hyperthermia (MFH)
The results of the TEM measurements are shown in the left row
where pure LA is observed, while the right row shows with
MNPs coated with LA. When NaCl was not added, MNPs were
distributed monodispersally without showing agglomerates.
However, large agglomerates of several hundred nanometers in
diameter were formed by adding 0.1 M NaCl. They also
indicate agglomerated MNPs aligned along chains that were
more pronounced for samples with higher concentrations of
NaCl [2], as seen in figures 6.
Figure 6. Mean hydrodynamic diameter (Z-Average) versus NaCl concentration and
Mean SLP values versus MNP sample iron concentration for non-agglomerated particles
(0.0 M NaCl) up to fully agglomerated MNP samples.
IV. CONCLUSIONES
In the 3 methods studied of magnetic hyperthermia, each one
presents evidence that it is possible to fight cancer with one of
these techniques, although it is still in development and
experimentation tests so that in the end it can be tested in
humans. a great advance to find materials such as zinc-calcium
ferrite, iron oxide magnetite (𝐹𝑒3 𝑂4 ), among others, and to find
analytical solutions possible to simulate them, taking into
account physical and chemical conditions and behaviors of both
the components that are being worked on magnetic
hyperthermia as of the malignant cells and without generating
any damage to healthy cells, besides being able to analyze these
laboratory results in the latest equipment such as: Transmission
Electron Microscopy (TEM), X-ray Diffraction (XRD),
Scanning Electron Microscopy (SEM) and Energy Dispersion
Spectroscopy (EDS), among other devices.
REFERENCES
[1] Rosario Argentina Jasso-Terán, Dora Alicia Cortés-Hernández,
Héctor Javier Sánchez-Fuentes, Pamela Yajaira Reyes-
Rodríguez, Laura Elena de León-Prado “Nanopartículas
magnéticas de zinc y calcio para aplicaciones en hipertermia
magnética” Facultad de Ingeniería (Fac. Ing.) Vol. 25 (42), pp.
89-98. Mayo-Agosto, 2016.
[2] Iordana Astefanoaei and Alexandru Stancu, "A Temperature
Analysis in Magnetic Hyperthermia," AIP Conf. Proc. 1916,
040009-1–040009-7; https://doi.org/10.1063/1.5017448.
[3] Ulrich Engelmann, Eva Miriam Buhl, Martin Baumann, Thomas
Schmitz-Rode and Ioana Slabu, “Agglomeration of magnetic
nanoparticles and its effects on magnetic hyperthermia”. Current
Directions in Biomedical Engineering 2017; 3(2): 457–
460;https://doi.org/10.1515/cdbme-2017-0096.