Nanohyperthermia of malignant tumors.i. lanthanum-strontium manganite magnetic fluid as potential inducer of tumor hyperthermia
Objectives: To synthesize magnetic particles of lanthanum-strontium manganite, prepare the magnetic fluid (MF), evaluate the generation of heat by particles and determine their common toxiсity. Methods: Nanoparticles based on the solid solutions of lanthanum-strontium manganite (La1-xSrxMnO3) have b...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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Solopan, S. Belous, A. Yelenich, A. Bubnovskaya, L. Kovelskaya, A. Podoltsev, A. Kondratenko, I. Osinsky, S. 2018-06-19T10:58:29Z 2018-06-19T10:58:29Z 2011 Nanohyperthermia of malignant tumors.i. lanthanum-strontium manganite magnetic fluid as potential inducer of tumor hyperthermia / S. Solopan, A. Belous, A. Yelenich, L. Bubnovskaya, A. Kovelskaya, A. Podoltsev, I. Kondtatenko, S. Osinsky // Experimental Oncology. — 2011. — Т. 33, № 3. — С. 130-135. — Бібліогр.: 37 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/138656 Objectives: To synthesize magnetic particles of lanthanum-strontium manganite, prepare the magnetic fluid (MF), evaluate the generation of heat by particles and determine their common toxiсity. Methods: Nanoparticles based on the solid solutions of lanthanum-strontium manganite (La1-xSrxMnO3) have been synthesized by a sol-gel method. Conventional methods of experimental oncology were used. Results: Nanoparticles of ferromagnetic materials on the basis of solid solutions of lanthanum strontium manganite by sol-gel method were synthesized. It was shown the possibility to regulate the aggregate form of particles that are formed during the synthesis. Magnetic fluid based on the synthesized nanoparticles and water solutions of agarose have been produced. It was shown the possibility to heat this magnetic fluid up to 42–45 °С in externally applied alternating magnetic field (AMF) operated at 100–400 kHz. It was determined that under long-term influence of AMF nanofluid is heated up to temperature which is not over that of magnetic phase transition. It was detected that magnetic powder as well as fluid have not displayed acute toxicity or side effects (intraperitoneal or intratumoral administration) in animals either intact or with transplanted tumors. Conclusions: Possibility of synthesized magnetic fluid to generate heat in externally applied AMF as well as lack of side effects allow to consider its as a potential mean for tumor hyperthermia (HT). This work was supported by STCU (grant #5213). en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Original contributions Nanohyperthermia of malignant tumors.i. lanthanum-strontium manganite magnetic fluid as potential inducer of tumor hyperthermia Article published earlier |
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Nanohyperthermia of malignant tumors.i. lanthanum-strontium manganite magnetic fluid as potential inducer of tumor hyperthermia |
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Nanohyperthermia of malignant tumors.i. lanthanum-strontium manganite magnetic fluid as potential inducer of tumor hyperthermia Solopan, S. Belous, A. Yelenich, A. Bubnovskaya, L. Kovelskaya, A. Podoltsev, A. Kondratenko, I. Osinsky, S. Original contributions |
| title_short |
Nanohyperthermia of malignant tumors.i. lanthanum-strontium manganite magnetic fluid as potential inducer of tumor hyperthermia |
| title_full |
Nanohyperthermia of malignant tumors.i. lanthanum-strontium manganite magnetic fluid as potential inducer of tumor hyperthermia |
| title_fullStr |
Nanohyperthermia of malignant tumors.i. lanthanum-strontium manganite magnetic fluid as potential inducer of tumor hyperthermia |
| title_full_unstemmed |
Nanohyperthermia of malignant tumors.i. lanthanum-strontium manganite magnetic fluid as potential inducer of tumor hyperthermia |
| title_sort |
nanohyperthermia of malignant tumors.i. lanthanum-strontium manganite magnetic fluid as potential inducer of tumor hyperthermia |
| author |
Solopan, S. Belous, A. Yelenich, A. Bubnovskaya, L. Kovelskaya, A. Podoltsev, A. Kondratenko, I. Osinsky, S. |
| author_facet |
Solopan, S. Belous, A. Yelenich, A. Bubnovskaya, L. Kovelskaya, A. Podoltsev, A. Kondratenko, I. Osinsky, S. |
| topic |
Original contributions |
| topic_facet |
Original contributions |
| publishDate |
2011 |
| language |
English |
| container_title |
Experimental Oncology |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| format |
Article |
| description |
Objectives: To synthesize magnetic particles of lanthanum-strontium manganite, prepare the magnetic fluid (MF), evaluate the generation of heat by particles and determine their common toxiсity. Methods: Nanoparticles based on the solid solutions of lanthanum-strontium manganite (La1-xSrxMnO3) have been synthesized by a sol-gel method. Conventional methods of experimental oncology were used. Results: Nanoparticles of ferromagnetic materials on the basis of solid solutions of lanthanum strontium manganite by sol-gel method were synthesized. It was shown the possibility to regulate the aggregate form of particles that are formed during the synthesis. Magnetic fluid based on the synthesized nanoparticles and water solutions of agarose have been produced. It was shown the possibility to heat this magnetic fluid up to 42–45 °С in externally applied alternating magnetic field (AMF) operated at 100–400 kHz. It was determined that under long-term influence of AMF nanofluid is heated up to temperature which is not over that of magnetic phase transition. It was detected that magnetic powder as well as fluid have not displayed acute toxicity or side effects (intraperitoneal or intratumoral administration) in animals either intact or with transplanted tumors. Conclusions: Possibility of synthesized magnetic fluid to generate heat in externally applied AMF as well as lack of side effects allow to consider its as a potential mean for tumor hyperthermia (HT).
|
| issn |
1812-9269 |
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https://nasplib.isofts.kiev.ua/handle/123456789/138656 |
| citation_txt |
Nanohyperthermia of malignant tumors.i. lanthanum-strontium manganite magnetic fluid as potential inducer of tumor hyperthermia / S. Solopan, A. Belous, A. Yelenich, L. Bubnovskaya, A. Kovelskaya, A. Podoltsev, I. Kondtatenko, S. Osinsky // Experimental Oncology. — 2011. — Т. 33, № 3. — С. 130-135. — Бібліогр.: 37 назв. — англ. |
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2025-11-27T02:26:03Z |
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2025-11-27T02:26:03Z |
| _version_ |
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| fulltext |
130 Experimental Oncology 33, 130–135, 2011 (September)
NANOHYPERTHERMIA OF MALIGNANT TUMORS.
I. LANTHANUM-STRONTIUM MANGANITE MAGNETIC FLUID
AS POTENTIAL INDUCER OF TUMOR HYPERTHERMIA
S. Solopan1,*, А. Belous1, A. Yelenich1, L. Bubnovskaya2,
A. Kovelskaya2, A. Podoltsev3, I. Kondratenko3, S. Osinsky2
1V.I. Vernadsky Insitute of General and Inorganic Chemistry, NAS of Ukraine, Palladin Ave. 32/34,
03680 Kiev, Ukraine;
2R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine,
Vasilkovskaya Str. 45, 03022, Kiev, Ukraine
3Institute of Electrodynamics, NAS of Ukraine, Peremoga Ave. 56, 03057, Kiev, Ukraine
Objectives: To synthesize magnetic particles of lanthanum-strontium manganite, prepare the magnetic fluid (MF), evaluate
the generation of heat by particles and determine their common toxiсity. Methods: Nanoparticles based on the solid solutions
of lanthanum-strontium manganite (La1-xSrxMnO3) have been synthesized by a sol-gel method. Conventional methods of experi-
mental oncology were used. Results: Nanoparticles of ferromagnetic materials on the basis of solid solutions of lanthanum stron-
tium manganite by sol-gel method were synthesized. It was shown the possibility to regulate the aggregate form of particles that
are formed during the synthesis. Magnetic fluid based on the synthesized nanoparticles and water solutions of agarose have been
produced. It was shown the possibility to heat this magnetic fluid up to 42–45 °С in externally applied alternating magnetic field
(AMF) operated at 100–400 kHz. It was determined that under long-term influence of AMF nanofluid is heated up to temperature
which is not over that of magnetic phase transition. It was detected that magnetic powder as well as fluid have not displayed acute
toxicity or side effects (intraperitoneal or intratumoral administration) in animals either intact or with transplanted tumors. Con-
clusions: Possibility of synthesized magnetic fluid to generate heat in externally applied AMF as well as lack of side effects allow
to consider its as a potential mean for tumor hyperthermia (HT).
Key Words: ferromagnetic materials, sol-gel synthesis, hyperthermia, magnetic fluid, nanosized particles.
Hyperthermia (HT) is applied in combination with
radiation and/or chemotherapy in the treatment of pa-
tients with severe malignant tumors more than 30 years
demonstrating significantly enhancement of therapy
outcome [1–5]. At the same time, some of the basic
problems of HT, in particular receiving the homoge-
neous distribution of temperature in tumor volume and
heating the deep-seated tumors are not resolved till
now despite of intensive efforts in the field of technical
arrangement of clinical HT.
Among the different approaches to overcome
above mentioned problems and enhance the HT ef-
ficacy the nanotechnology seems to be the most prom-
ising. At the present time the studies dedicated to the
synthesis of magnetic nanoparticles for the biomedical
applications are became the more and more intensive.
Organic and inorganic nanoparticles are widely used
in the diagnostics and treatment of various diseases,
in particular neoplastic one [6–8]. Special inter-
est is focused on the ferromagnetic nanoparticles
that can be heated by externally applied alternating
magnetic field resulting in the heating of tumor tissue
[9–11]. It was shown that the application of magnetic
nanoparticles in the combined cancer treatment allows
to enhance the therapy efficacy [12–17].
Up to date, the most common magnetic materials
for tumor hyperthermia as well as for drug delivery
are magnetite (Fe3O4) and maghemite (γ-Fe2O3) the
biocompatibility of which are well known [11, 18, 19].
It has to be mentioned that the highest achieve-
ments in the field of nanohyperthermia were received
by Jordan et al. [13, 15, 16]. They have elaborated the
method of local heating of tumor by means of magnetic
fluid (Fe3O4 particles with 15–20 nm in size) that was
injected into the tumor followed by exposition of tumor
to an alternating magnetic field (100 kHz frequency)
that resulted in the increase of tumor temperature
up to 44–45 °C. The coating of nanoparticles by amino-
sylane forms the preventive “sleeve” around the core
of iron oxide that helps to particles to be absorbed
by tumor cells in more significant amount and to avoid
the withdrawal from tumor [11, 17].
It has to be noted that one problem is discussed now
very actively, namely the possible negative influence
of ferromagnetic materials with high Curie temperature
on hyperthermic procedure, in particular excessive
heating of surrounding healthy tissues and other side
effects by the exploitation of the following nanopar-
ticles: Fe3O4 (585 °C), γ-Fe2O3 (447 °C), CoFe2O4 (518 °C),
ZnFe2O4 (545 °C) and BaFe12O19 (580 °C) [20, 21].
Nanoparticles with the phase transition in the
temperature range 42–45 °C that are optimal for the
destruction of malignant tumors, may be exploited
as safety alternative for tumor HT. The heterosub-
situte lanthanum-strontium manganites were con-
sidered as a very promising to achieve this aim:
La1-xAxMnO3 (where A = Ag, Ba, Ca, Na, Sr) [22–25].
Received: July 26, 2011.
*Correspondence: E-mail — solopan@ukr.net
Abbreviations: AMF — alternating magnetic field; HT — hyperthermia.
Exp Oncol 2011
33, 3, 130–135
Experimental Oncology 33, 130–135, 2011 (September) 131
These substances demonstrate the ferromagnetic
effect in the range of x=0.25–0.5 with Curie point =
0–95 °C.
On the current days there is a large number
of methods for nanosized ferromagnetic materials
preparation. One of the promising methods is a sol-
gel method, the use of which can produce crystal
nanoparticles and decrease the temperature of the
single-phase product synthesis.
Moreover, there is very important to create on the
basis of ferromagnetic nanoparticles the magnetic flu-
ids (MF) which could be heated by the exposition to AMF
and characterized by high level of biocompatibility.
The current study was aimed to synthesize magnet-
ic particles of lanthanum-strontium manganite, evalu-
ate structural and electrical properties of nanosized
particles, create the ferromagnetic fluid, determine
their heating by AMF, and assess of MF toxicity in vivo.
MATERIALS AND METHODS
Synthesis of nanoparticles. Samples of the solid
solution La1-xSrxMnO3 (xSr = 0.225–0.3), have been syn-
thesized by the sol-gel method [26, 27]. Water-soluble
salts La(NO3)3, Sr(NO3)2, Mn(NO3)2 were used as start-
ing reagents. Calculated amounts of reagents were
dissolved in distilled water. Citric acid and ethylene
glycol as gelling additives were added to the solution.
When the mixture is heated at 80 °C, polyesterifica-
tion occurs with the formation of polymeric gel. Then
the temperature increased up to 200 °C, and powder
of La1-xSrxMnO3 precursor was formed as a result
of pyrolysis. Heat treatment of obtained powders of
“precursor” was performed in the temperature range
400–1100 °C in a crucible from Al2O3 in the air for 2–4 h.
For comparison, the control samples have been also
synthesized by the method of solid state reactions and
by precipitation from solution. Synthesis of samples
by solid-state reactions were carried out as described
in [28]. Synthesis of the samples by precipitation from
solution was carried out as described in [29].
Physic-technical methods. X-ray diffraction
(XRD) measurements were carried out on a “DRON-
4–07” diffractometer (CuKα radiation) in the range
of 2θ = 10–150 °C.
Alternating magnetic field. A high frequency gen-
erator produced by Institute of Electrodynamics was
used to induce an alternating current of 70 A at a fre-
quency of 100–440 kHz. The equipment is shown
in Fig. 1. The current passes through a custom-made
five-turn water-cooled coil of 30 mm in internal di-
ameter and 30 mm in height to generate a magnetic
field inside the coil. The electromagnetic field within
this coil is not uniform. The sample with magnetic
fluid was placed on a platform in a center inside the
coil with maximum magnetic field strength above
7.7 kA/m (Fig. 2, a, 2, b, and 2, c). According to the
heating mechanisms of nanoparticle hyperthermia,
the induced energy generation rate is approximately
proportional to H2. But a characteristic size of the
sample was relatively small (8 mm in diameter and
15 mm in height), and a variation of the magnetic field
inside the whole sample can be considered negligible.
Fig. 1. Experimental setup consisting of a high frequency gen-
erator (a) and coil (b)
8000
7000
6000
5000
4000
3000
2000
1000
0
0 0.03
M
ag
ne
tic
fi
el
d,
n
or
m
, A
/m
0.040.02 0.06 0.080.01 0.05
Coil
0.07
1
0.8
0.6
0.4
0.2
0
-0.2
-0.4
0 0.015
M
ag
ne
tic
fi
el
d,
z
co
m
po
ne
nt
, A
/m
×
10
4
0.020.01 0.03 0.040.005 0.025
Coil
0.035
a
b
c
Fig. 2. Distribution of magnetic field |H| in the coil (a) and
magnetic field HZ on the vertical (b) and horizontal (c) axis
of symmetry
Temperature measurement. The temperature
monitored by fine thermocouple (copper-constantan)
were recorded every 60 s during the entire experiment.
At this moment the high frequency generator was turn
off at a small interval of time ~5 s.
132 Experimental Oncology 33, 130–135, 2011 (September)
Biological studies. In accordance with the meth-
odological instructions the normal animals have been
used in this study. The experiments were conducted
with intact С57Bl/6 mice (bred of Institute of Experi-
mental Pathology, Oncology and Radiobiology), males
with body weight of 20–22 g. There were 6 animals
in each experimental group. It was used 30 normal
mice to determine the acute toxicity, 8 Lewis lung
carcinoma-bearing mice (C57Bl/6, male, 20–22 g,
intramuscular transplantation) and 15 Guerin carcino-
ma-bearing rats (IEPOR bred, female, 170–200 g, sub-
cutaneous translpantation). All experiments had been
approved by the regional animal ethics committee.
RESULTS AND DISCUSSION
According to the method of sol-gel synthesis,
the addition of gel-forming substances to the salts
of metals and subsequent heating results in the series
of processes in solution, in particular the formation
of heteronuclear metal complexes with citric acid
as well as citric acid polymerization with ethylene
glycol described in the literature [27, 30, 31]. The
polymerization of the gel was carried out at different
pH. The solution of ammonia was added into obtained
gel to change pH with the following evaporation of so-
lutions to obtain a powder “precursor”. The powders
obtained at different pH and temperatures of heat-
treatment were investigated by X-ray and electron
microscopy (Fig. 3 and 4).
As shown in Fig. 3, a, the broad halo in the field
of 2θ = 20–25° is observed for the powder “precursor”
synthesized in acidic environment (pH = 1.5) at 400 °C,
that indicates its amorphous state. Further heat-treat-
ment leads to the crystallization of the sample that was
initiated in the temperature range of 500–600 °C. After
heat treatment at 800 °C the sample is a single phased
according to X-ray analysis, but a slight broadening
of the main peaks were observed on X-ray slides. At the
same time, according to electron microscopic studies
(Fig. 4, a), the investigated particles have amorphous
and crystalline regions, that is also confirmed by elec-
tron diffraction analysis. After analyzing the results
of electron diffraction of amorphous particles as well
as X-ray data it was concluded that the amorphous
regions, which are observed in the agglomerates are
carbon that is not oxidized during the pyrolysis of gel.
Detailed microstructural analysis of crystalline par-
ticles showed that their sizes are within 20–50 nm. The
particles form dense agglomerates with size ranged
500–2000 nm.
According to X-ray analysis for samples obtained
at a pH of the gel, equal to 6 (Fig. 3, b), after heat treat-
ment at 400 °C there is a somewhat different picture,
namely, the samples are partially amorphous and
partially crystalline, as evidenced by an amorphous
halo in the field of 2θ = 20–25 °C, as well as the pres-
ence of broad peaks, indicating the beginning of the
formation of crystalline compounds.
The micrographs and electron diffraction data for
solid solution La0.775Sr0,225MnO3, synthesized at pH
= 6 after heat treatment at 800 °C were presented
on Fig. 4, b. For this sample, the formation of agglomer-
ates consisting from smaller units, occurs which, in turn,
are formed from the nanoparticles. These agglomerates
are formed by the crystal particles and have not the
amorphous phase, unlike the previous model. As seen
from the microphotograhs, the size of the particles that
form the agglomerates is 50–70 nm.
The X-ray powder diffraction patterns of samples
obtained at gel pH=9 (Fig. 3, c) after heat treatment
contain only crystalline particles. X-ray peaks are nar-
row, indicating a high degree of sample crystallinity. For
a solid solution La0.775Sr0,225MnO3, synthesized at pH =
9, after heat treatment at 800 °C, the formation of “soft”
slightly-agglomerated powders with a loose structure
of the agglomerates, in which the particles have a size
of about 40–50 nm (Fig. 4, c) was observed. In this case,
as seen from the figure, the particles are fully crystal.
In accordance with Brinker and Scherer, and Kabi-
hana [31, 32], observed pH influence is associated with
10 25 30
3
2
1
20 40 2θ15 35 5045 55
10 25 30
3
2
1
20 40 2θ15 35 5045 55
10 25 30
3
2
1
20 40 2θ15 35 5045 55
a
b
c
Fig. 3. X-ray patterns of precursor for receiving of solid solution
La0.775Sr 0,225MnO3 after thermotreatment at different temperature:
400 °С (1); 600 °С (2); 800 °С (3). Gel pH ~ 1.5 (a), 6 (b), 9 (c)
Experimental Oncology 33, 130–135, 2011 (September) 133
the fact that the formation of metal complexes with citric
acid and their subsequent polymerization with ethylene
glycol under acidic environment (pH=1.5) was occurred.
Under alkaline environment (pH=9), the formation of hy-
droxides of metals and their interaction with the polymer
gel is caused by the formation of hydrogen bonds.
It should be noted that the formation of single-
phased crystal structure by using the method of solid
state reactions occurs in the temperature range
1000–1150 °C while the precipitation from solutions the
single-phase crystalline structure is formed at 1350 °C,
which is consistent with Belous et al. [29].
Our studies have shown that using the proposed
method of sol-gel synthesis of solid solutions of the
system La0.775Sr0.225MnO3 the single-phased crystal
structure begins to be formed at 500–600 °C, and
at 800 °C the samples are fully crystal (Table). The
particle size is about 40–50 nm. On the basis of syn-
thesized nanoparticles La0.775Sr0.225MnO3 the magnetic
fluid was obtained where the aqueous solutions of aga-
rose as gel-forming component was used.
The results of investigations of “agarose” aqueous
solution viscosity and the maximum permissible viscos-
ity of fluids in living organisms have shown in Fig. 5 [33].
It was concluded that the optimum concentration of base
material (agarose) should not exceed 0.06%. The mag-
netic particles of a solid solution of La0.775Sr0.225MnO3,
synthesized both by solid state reaction method and
sol-gel method with different temperatures of heat-
treatment (Tterm = 800, 900, 1000, 1100, 1150°C) were
used to evaluate the influence of magnetic properties
of the substance on magnetic fluid heating.
0,000 0,025 0,050 0,075 0,100 0,125 0,150
0
2
4
6
8
10
12
14
%
Maximum permissible viscosity of fluids
introduced into living organism
υ,
м
м2 /с
Fig. 5. Dependence of gel viscosity prepared by means of aga-
rose on the basic substance concentration
Table. Phase composition of manganites La0.775Sr0.225MnO3 powders according to conditions of synthesis and thermotreatment temperature*
Т, К Solid phase synthesis Synthesis by precipitation from solutions Sol-gel
synthesis
870 Mn2O3(100), La2O3(78), SrCO3(57), La(OH)3(32),** SrO(32), P(8),
SrMnO3(8)
P(100), La2O2CO3(44), Sr2MnO5(32), Sr2MnO4(16), Mn2O3(14),
SrCO3(3)
P(100)
970 Mn2O3(100), La2O3(78), SrCO3(57), La(OH)3(32),** SrO(32), P(8),
SrMnO3(8)
P(100), La2O2CO3(44), Sr2MnO5(32), Sr2MnO4(16), Mn2O3(14),
SrCO3(3)
P(100)
1070 La2O3(100), Mn2O3(97), P(72), a-SrMnO3(13) P(100), Sr2Mn2O5(12), La(OH)3(11), Mn2O3(9), (La1-ySry)2MnO4(7),
La2O2CO3(5)
P(100)
1170 P(100), Mn2O3(33), La(OH)3(14), a-SrMnO3(5), SrCO3(3), SrO(3) P(100), Sr2Mn2O5(7), La(OH)3(4), (La1-ySry)2MnO4(4), La2O2CO3(1) P(100)
1270 P(100), La2O3(11), a-SrMnO3(3), Mn3O4(1.5) P(100), Sr2Mn2O5(4), (La1-ySry)2MnO4(2), La2O2CO3(0.7) P(100)
1320 P(100), La2O3 (traces) – P(100)
1370 P(100) P(100), Sr2Mn2O5(4), (La1-ySry)2MnO4(1.7), La2O2CO3(0.6) P(100)
1570 P(100) P(100), (La1-ySry)2MnO4(1), La2O2CO3(traces) P(100)
1620 P(100) P(100) P(100)
*Numbers in parentheses — relative intensity of most reflexes in corresponding phases (%);
**Appearance of La(OH)3 is caused by La2O3 absorption of water from air under storage; P — perovskite.
b
c
Crystalline
particles
Amorphous
particles
a
Fig. 4. Microphotographs of particles of solid solution
La0.775Sr0,0225MnO3 synthesized at 800 °C during 2 h. Gel pH
~ 1,5 (a), 6 (b), 9(c)
134 Experimental Oncology 33, 130–135, 2011 (September)
AMF resting. The heating of magnetic fluids were
carried out in an alternating magnetic field in the
frequency range of 100–400 kHz. It was determined
that the heating of magnetic fluids of all prepared
samples to a constant temperature was observed
during 20 minutes (Fig. 6). It was also shown that the
temperature of the synthesis of magnetic particles
impact on the heating temperature of magnetic fluids.
This regularity can be explained by changes in the
ratio Mn3+/Mn4+ [34–36], which results in the change
of Curie tempe rature and conductivity as well as par-
ticle sizes [37]. The dependence of the magnetization
of La0.775Sr0.225MnO3, synthesized by sol-gel method
at pH = 9, from the magnetic field parameters was
evaluated. It was found that the coercitive force of this
powder (Hc) is 2834.39 A/m, and the magnetization
(Ms) is 4.79 Gc cm3/g, whereas the theoretical Ms for
its is 91.5 Gc cm3/g.
Toxicity of magnetic fluid. It was determined the
maximal tolerable dose (MTD) in accordance with in-
structions. Conventional indices of acute toxicity, such
as LD10, LD50, LD100 could not been determined be-
cause of low toxicity of tested substance that resulted
in the necessity to apply of overdoses of nanopowder.
МTD was determined as a dose that does not results
in the death of no one animal in the group and at the
same time does not provoke body weight loss not
more than 10%. The substance that results in the body
weight loss more than 10% is considered toxic. In order
to designate the toxicity of the substance each animal
was weighed before it administration and every day
after up to the end of experiment.
0 5 10 15 20 25
65
60
55
50
45
40
35
30
25
t, min
f = 300 kHz
T,
°C
Fig. 6. Time-dependent heating of MF, based on agarose
and La0.775Sr0.225MnO3, induced with AMF (300 kHz, strength
of 7.1 kA/m). 1, 2 — the samples were synthesized by the method
of solid-phase reaction at 1200 and 1150 0C, respectively; 3, 4,
5, 6 — the samples were synthesized by sol-gel method at 900,
800, 1000 and 1100 0C, respectively. The shaded area indicates
the optimal temperature for tumor hyperthermia
Magnetic fluid (sol-gel method, Tterm = 800 °C)
was administered into the mice at the doses of 100,
200, 300 and 400 mg of powder of nanoparticles/
kg of body weight. It was given intraperitoneally,
in a single dose. Duration of observation under every
group was 14 days.
Under the administration of this substance at the
doses of 50 and 100 mg/kg body weight loss was not
observed on the 1st day after. On the contrary it was
observed body weight increase gradually up to the end
of experiment and approximately on 26±3.0% more
that it was before substance administration.
Beginning from a dose of 200 mg/kg it was ob-
served inconsequential body weight loss on the 1st
day after injection — by 1.6±0.4% compare with
the initial ones and than body weight loss increased
with the increase of doses administered: at a dose
of 300 mg/kg — by 7.5±1.5%, at a dose of 400 mg/
kg — by 8.5±2.1%.
At a dose of 200 mg/kg as early as on the 4th day
after injection it was observed that body weight was
not only restored but it was going on gradual increasing
by 25±2.1% up to the end of experiment.
At a dose of 300 mg/kg rather substantial body
weight loss 7.5±1.5% was registered already on the
1st day after. On the 2nd and 3rd days animal body
weight started to restore gradually but not substan-
tial: by 2.45±0.9% and by 2.1±0.6%, respectively.
Beginning from the 4th day after injection body weight
of almost all mice returned to the initial level and then
started to be increased by 6.8±0.5% and 9.1±1.8%
on the 4th and 7th days, respectively.
Dose of 400 mg/kg of body weight caused the most
substantial body weight loss by 8.5 ±2.3% on the 1st
day after injection and continue to be observed on the
2nd, 3rd and 4th day: by 5.3±2.1%, 2.3 ±1.7% and
1.6 ±0.7%, respectively, in comparison with initial body
weight of the mice. In further it was observed that body
weight loss gradually started to delay and beginning
from the 7th day mice body weight was increased
by 3.3±1.1% and at the end of the experiment (at the
14th day) it was 5.6±2.8% higher.
On the grounds of the obtained results it was pos-
sible to make the conclusion that maximum tolerable
dose (MTD) is 300 mg/kg of body weight.
In conclusion, the nanoparticles of a solid solu-
tion La0.775Sr0.225MnO3 produced by sol-gel method
was synthesized and magnetic fluid on their basis
prepared. It was shown the possibility to control the
size and aggregate state of particles by changing the
synthesis conditions. The physical parameters of the
synthesized nanoparticles were evaluated, and it was
shown the change of the phase transition temperature
from ferromagnetic to paramagnetic state for the
synthesized nanoparticles. The possibility to heat the
magnetic fluid obtained on the basis of mentioned
nanoparticles up to 42–45 °C in an alternating mag-
netic field was demonstrated. It was also established
that the temperature of heated fluid was not exceeded
the temperature of magnetic phase transition under
prolonged exposure to AMF.
It was determined that synthesized nanoparticles
of lanthanum strontium manganite (La 0.775Sr0.225MnO3)
did not display the toxicity or provoked the side effects
being administered intraperitoneally into the experi-
mental animals neither intact nor with transplanted
tumors. Maximum tolerable dose (MTD) of nanopow-
der is 300 mg/kg of body weight.
Experimental Oncology 33, 130–135, 2011 (September) 135
ACKNOWLEDGEMENTS
This work was supported by STCU (grant #5213).
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