Department of Physics and Astronomy, University of Texas at Brownsville, USA
*Corresponding author:
Karen S. Martirosyan
Department of Physics and
Astronomy
University of Texas at Brownsville
80 Fort Brown, SETB 2.258,
Brownsville
TX, 78520, USA E-mail: karen.martiroyan@utb.edu
Received July 10, 2012; Accepted July 10, 2012; Published July 12, 2012
Citation: Martirosyan KS (2012) Thermosensitive Magnetic Nanoparticles for
Self-Controlled Hyperthermia Cancer Treatment. J Nanomed Nanotechol 3:e112.
doi:10.4172/2157-7439.1000e112
Magnetic nanoparticles show remarkable phenomena such as
superparamagnetism, high field irreversibility and high saturation
magnetization [1]. The study of magnetic nanoparticles has been a
very active research field due to many important applications such
as drug delivery, imaging and hyperthermia cancer treatment [2].
Hyperthermia has been used for many years to treat a wide variety of
tumors in patients and used as well as an adjunct to cancer radiotherapy
or chemotherapy [3,4]. Its use is based on the fact that tumor cells are
more sensitive to temperature in the range of 42–45°C (which yields
necrosis, coagulation, or carbonization) than normal tissue cells.
This temperature range has become critical for cancer treatment due
to damaging the cancerous cells without altering the healthy cells by
selective heating (up to 45°C) and controlling heating rate and time.
Basically, hyperthermia increases perfusion and oxygenation
of neoplastic hypoxic cells, which are more resistant to ionizing
radiation than normal cells [5]. Moreover, increased tumor tissue
perfusion facilitates the absorption of chemotherapeutic drugs
through cell membrane without being more toxic [6-8]. As a result,
the action of combination of hyperthermia with radiotherapy or
chemotherapy becomes more efficient. Consequently, hyperthermia
allows reducing of tumors resistant to various chemotherapeutic
drugs such as doxorubicin, cisplatin, bleomycin, nitrosoureas, and
cyclophosphamide. It has been demonstrated that hyperthermia also
has an anti-angiogenic action and an immunotherapeutic role, due to
thermal shock proteins, which are produced by stressed tumor cells
[9,10]. This method has found clinical application mostly in Europe
and Asia [4,8]. While in the United States, microwave hyperthermia in
conjunction with radiation has received approval from the Food and
Drug Administration (FDA), it still remains mostly as an experimental
method due to possible overheating and necrosis of normal tissue
[11,12]. There is an urgent need for development of new hyperthermia
heating agents and treatment methodologies that will be more effective
than those currently available and help to unlock the full potential of
the technology that can have a significant impact on management of
cancer patients. Thus, it is of paramount importance to develop new
nanostructured media, which would enable selective heating of tumor
cells and vasculature avoiding excessive damage to healthy tissue
structures.
Magnetic fluids based on iron oxide (Fe3O4), stabilized by
biocompatible surfactants are typically used as heating agent in
magnetic hyperthermia [13,14]. In the presence of AC magnetic
field, magnetic nanoparticles show three different types of losses
- Hysteresis, Ne´el, and Brownian, which are responsible for heat
generation. However, significant limitations of using commercial
available magnetic nanoparticles are non-selectivity and overheating
of surrounding normal tissues. For most nanoparticles suggested so
far for cancer hyperthermia treatment, uniform controlled induction
heating and selectivity remain as major challenges.
There is increasing number of research articles for self-controlled
hyperthermia and development of nanoparticles with Curie
Temperature (Tc) in the range of 45-50°C that are not affected by alternating magnetic fields above 50°C in order to prevent overheating
of normal cells [15-26]. Various nanoparticles were synthesized using
physical as well as chemical methods. For example, ultrafine alumina
coated particles of substituted ferrite Co1−xZnxFe2O4 and yttrium–
iron garnet Y3Fe5−x AlxO12 have been proposed to tailor Tc at ~50°C
[16]. Copper nickel (CuNi) alloy nanoparticles with varying Tc from
40 to 60°C were synthesized by several techniques [17]. In vitro and
in vivo animal experiments have demonstrated the feasibility of the
temperature-controlled heating of the tissue, laden with the particles,
by an external alternating magnetic field. Nickel-Chromium (Ni1-
xCrx) particles with varying compositions have been investigated as
thermoseeds for use in localized self controlled hyperthermia treatment
of cancer [18]. A series of Ni-Cr alloys, have been prepared to find the
specific composition that has Curie temperature in range of 43-44°C.
The samples were cast by arc melting technique then annealed at 850°C
for 5 hours in sealed quartz tubes. The Curie temperatures of the alloys
decreased almost linearly with increasing Cr concentration from 4.54
to 5.9 wt%. The results showed that Ni1-xCrx alloys might be good
candidates for self controlled magnetic hyperthermia applications.
Structural and magnetic properties have been studied for Gd5(Si1−xGex)4 and (Gd1−xRx)5Si4 series, with R = Ce Nd, Er, and Ho, in the
context of their use as magnetic materials in the self-controlled
hyperthermia treatment of cancer [19]. The study shows that these
materials have high magnetization values and their magnetic ordering
temperatures can be varied linearly over a broad range by adjusting
the composition of the constituent elements. The high magnetization
and optimal Tc values of these composites meets self-controlled
hyperthermia requirements.
La-Ag and La-Na perovskite manganites were proposed [20] as
smart mediators for self-controlled isothermal heating in magnetic
hyperthermia. It shows that dissipation of the alternating magnetic
field energy causes heating of aqueous suspensions to terminate
at 42-48°C without external temperature control. Ferromagnetic
La0.73Sr0.27MnO3 nanoparticles (20–100 nm) showed saturation
magnetization ~38 emu/g at 20 kOe with TC value of 45°C [21].
Unaggregated La0.82Sr0.18MnO3+δ perovskite nanoparticles with a mean
crystallite size of 22 nm were successfully synthesized through an
aqueous combustion synthesis, which takes advantage of exothermic,
fast and self-sustaining chemical reactions between metal nitrates
and glycine [22]. Fast calcination and milling process were used to enhance crystallinity of the nanoparticles and their desaggregation. The
heating experiments of magnetic fluid suspended La0.82Sr0.18MnO3+δ
nanoparticles in AC magnetic field demonstrated that the particles can
be used for self-controlled hyperthermia application, considering their
maximum heating temperature ~43°C. Recently, it was shown that
complex ferrites nanoparticles with formula Mg1+xFe2-2xTixO4, (where
0≤x≤0.5) can be meet self-controlled hyperthermia requirements with
Tc in range of 45-50°C [23-24]. Furthermore, authors [25] confirmed
that Curie temperature for Zn doped Mn-ferrite, Mn1-xZnxO and
the Gd doped Zn-ferrite, ZnGdxFe2-xO4 nanoparticles can be tuned
to the optimum temperature of 43°C. The Mg-Fe-Ti compositions
are very promising, since all the elements biocompatible. Magnetic
nanocomposite Ni0.2Ca0.8Gd0.08Fe1.92O4 encapsulated by poly vinyl
alcohol and synthesized by a two steps chemical reaction including solgel
combustion and solvent casting technique also can be applicable for
self controlled hyperthermia [26].
Thus, the magnetic materials with Curie temperature ~45°C,
having sufficient biocompatibility are the best candidates for effective
cancer hyperthermia treatment to avoid overheating. Because of
unique capability of turning on and off the magnetic properties
depending on temperature, the tumors will be continuously heated
at a self-controlled temperature equal to the Curie temperature of
the magnetic nanoparticles. This approach will allow to heat the
tumor cells and vasculature selectively and to prevent overheating
with subsequent damage to neighboring healthy tissues. Additionally,
the self-controlled method might allow in situ MRI monitoring and
selective hyperthermic therapy.
OMICS Publishing Group is the member of / publishing partner of/source content provider to
OMICS Publishing Group, An Open Access Publisher and Scientific Events Organizer for the Advancement of Science & Technology. All Published content, except where otherwise noted, is licensed under a Creative Commons Attribution License
Please ensure that you are using the latest version of Adobe reader. If you do not have this software installed on your system, you can download the free Adobe Reader by simply clicking on the following link: http://www.adobe.com/products/acrobat/readstep2.html
