Nanohyperthermia of malignant tumors. II. In vivo tumor heating with manganese perovskite nanoparticles
Objectives: To evaluate the ability of manganese perovskite nanoparticles (lanthanum-strontium manganite) to heat the tumor tissue in vivo under action of external alternating magnetic field. Materials and Methods: The magnetic fluid on the basis of nanoparticles of perovskite manganite was tested i...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2012
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| Цитувати: | Nanohyperthermia of malignant tumors. II. In vivo tumor heating with manganese perovskite nanoparticles / L. Bubnovskaya, A. Belous, A. Solopan, A. Podoltsev, I. Kondratenko, A. Kovelskaya, T. Sergienko, S. Osinsky // Experimental Oncology. — 2012. — Т. 34, № 4. — С. 336-339. — Бібліогр.: 14 назв. — англ. |
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irk-123456789-1398762018-06-22T03:05:09Z Nanohyperthermia of malignant tumors. II. In vivo tumor heating with manganese perovskite nanoparticles Bubnovskaya, L. Belous, A. Solopan, A. Podoltsev, A. Kondratenko, I. Kovelskaya, A. Sergienko, T. Osinsky, S. Original contributions Objectives: To evaluate the ability of manganese perovskite nanoparticles (lanthanum-strontium manganite) to heat the tumor tissue in vivo under action of external alternating magnetic field. Materials and Methods: The magnetic fluid on the basis of nanoparticles of perovskite manganite was tested in the heating experiments using of alternating magnetic field of frequency 300 kHz and amplitude 7.7 kA/m. Guerin carcinoma was transplanted into the muscle of rat. Magnetic fluid was injected intramuscularly or intratumorally. Temperature was measured by copper-constantan thermocouple. Results: Temperature of magnetic fluid was increased by 56 °C for 10 min of alternating magnetic field action. Administration of magnetic fluid into the muscle followed by alternating magnetic field resulted in the elevation of muscle temperature by 8 °C after 30 min post injection. Temperature of the tumor injected with magnetic fluid and treated by alternating magnetic field was increased by 13.6 °C on the 30 min of combined influence. Conclusion: In vivo study with rat tissue has demonstrated that magnetic fluid of manganite perovskite injected in the tumor increases the tumor temperature under an alternating magnetic field. Obtained results emphasize that magnetic fluid of manganite perovskite can be considered as effective inducer of tumor hyperthermia. 2012 Article Nanohyperthermia of malignant tumors. II. In vivo tumor heating with manganese perovskite nanoparticles / L. Bubnovskaya, A. Belous, A. Solopan, A. Podoltsev, I. Kondratenko, A. Kovelskaya, T. Sergienko, S. Osinsky // Experimental Oncology. — 2012. — Т. 34, № 4. — С. 336-339. — Бібліогр.: 14 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/139876 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Original contributions Original contributions |
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Original contributions Original contributions Bubnovskaya, L. Belous, A. Solopan, A. Podoltsev, A. Kondratenko, I. Kovelskaya, A. Sergienko, T. Osinsky, S. Nanohyperthermia of malignant tumors. II. In vivo tumor heating with manganese perovskite nanoparticles Experimental Oncology |
| description |
Objectives: To evaluate the ability of manganese perovskite nanoparticles (lanthanum-strontium manganite) to heat the tumor tissue in vivo under action of external alternating magnetic field. Materials and Methods: The magnetic fluid on the basis of nanoparticles of perovskite manganite was tested in the heating experiments using of alternating magnetic field of frequency 300 kHz and amplitude 7.7 kA/m. Guerin carcinoma was transplanted into the muscle of rat. Magnetic fluid was injected intramuscularly or intratumorally. Temperature was measured by copper-constantan thermocouple. Results: Temperature of magnetic fluid was increased by 56 °C for 10 min of alternating magnetic field action. Administration of magnetic fluid into the muscle followed by alternating magnetic field resulted in the elevation of muscle temperature by 8 °C after 30 min post injection. Temperature of the tumor injected with magnetic fluid and treated by alternating magnetic field was increased by 13.6 °C on the 30 min of combined influence. Conclusion: In vivo study with rat tissue has demonstrated that magnetic fluid of manganite perovskite injected in the tumor increases the tumor temperature under an alternating magnetic field. Obtained results emphasize that magnetic fluid of manganite perovskite can be considered as effective inducer of tumor hyperthermia. |
| format |
Article |
| author |
Bubnovskaya, L. Belous, A. Solopan, A. Podoltsev, A. Kondratenko, I. Kovelskaya, A. Sergienko, T. Osinsky, S. |
| author_facet |
Bubnovskaya, L. Belous, A. Solopan, A. Podoltsev, A. Kondratenko, I. Kovelskaya, A. Sergienko, T. Osinsky, S. |
| author_sort |
Bubnovskaya, L. |
| title |
Nanohyperthermia of malignant tumors. II. In vivo tumor heating with manganese perovskite nanoparticles |
| title_short |
Nanohyperthermia of malignant tumors. II. In vivo tumor heating with manganese perovskite nanoparticles |
| title_full |
Nanohyperthermia of malignant tumors. II. In vivo tumor heating with manganese perovskite nanoparticles |
| title_fullStr |
Nanohyperthermia of malignant tumors. II. In vivo tumor heating with manganese perovskite nanoparticles |
| title_full_unstemmed |
Nanohyperthermia of malignant tumors. II. In vivo tumor heating with manganese perovskite nanoparticles |
| title_sort |
nanohyperthermia of malignant tumors. ii. in vivo tumor heating with manganese perovskite nanoparticles |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2012 |
| topic_facet |
Original contributions |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/139876 |
| citation_txt |
Nanohyperthermia of malignant tumors. II. In vivo tumor heating with manganese perovskite nanoparticles / L. Bubnovskaya, A. Belous, A. Solopan, A. Podoltsev, I. Kondratenko, A. Kovelskaya, T. Sergienko, S. Osinsky // Experimental Oncology. — 2012. — Т. 34, № 4. — С. 336-339. — Бібліогр.: 14 назв. — англ. |
| series |
Experimental Oncology |
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2025-07-10T09:17:32Z |
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2025-07-10T09:17:32Z |
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336 Experimental Oncology 34, 336–339, 2012 (December)
NANOHYPERTHERMIA OF MALIGNANT TUMORS.
II. IN VIVO TUMOR HEATING WITH MANGANESE PEROVSKITE
NANOPARTICLES
L. Bubnovskaya1, A. Belous2, A. Solopan2, A. Podoltsev3,
I. Kondratenko3, A. Kovelskaya1, T. Sergienko1, S. Osinsky1,*
1R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv
03022, Ukraine
2V.I. Vernadsky Institute of General and Inorganic Chemistry, NAS of Ukraine, Kyiv 03680, Ukraine
3Institute of Electrodynamics, NAS of Ukraine, Kyiv 03057, Ukraine
Objectives: To evaluate the ability of manganese perovskite nanoparticles (lanthanum-strontium manganite) to heat the tumor tis-
sue in vivo under action of external alternating magnetic field. Materials and Methods: The magnetic fluid on the basis of nanopar-
ticles of perovskite manganite was tested in the heating experiments using of alternating magnetic field of frequency 300 kHz and
amplitude 7.7 kA/m. Guerin carcinoma was transplanted into the muscle of rat. Magnetic fluid was injected intramuscularly
or intratumorally. Temperature was measured by copper-constantan thermocouple. Results: Temperature of magnetic fluid was
increased by 56 °C for 10 min of alternating magnetic field action. Administration of magnetic fluid into the muscle followed by al-
ternating magnetic field resulted in the elevation of muscle temperature by 8 °C after 30 min post injection. Temperature of the
tumor injected with magnetic fluid and treated by alternating magnetic field was increased by 13.6 °C on the 30 min of combined
influence. Conclusion: In vivo study with rat tissue has demonstrated that magnetic fluid of manganite perovskite injected in the
tumor increases the tumor temperature under an alternating magnetic field. Obtained results emphasize that magnetic fluid of man-
ganite perovskite can be considered as effective inducer of tumor hyperthermia.
Key Words: manganese perovskite, magnetic fluid, alternating magnetic field, tumor, hyperthermia.
In the previous publication it was shown the pos-
sibility of synthesized magnetic fluid based on lantha-
num-strontium manganite nanoparticles to generate
the heat in externally applied alternating magnetic field
(AMF) in vitro as well as lack of side effects of magnetic
fluid administered into both non-tumor and tumor-
bearing mice and rats [1]. The proposition to use the
nanoparticles of perovskite manganite in the tumor
hyperthermia is based on the postulate that these
nanoparticles are able to demonstrate the ferromag- the ferromag-the ferromag- ferromag-ferromag-
netic effect in the range of x=0.25–0.5 with Curie point
= 0–95 �C that allows to avoid the overheating of sur- �C that allows to avoid the overheating of sur-
rounding normal tissues [2–7]. Samples of proposed
nanocomposites were received in some laboratories,
and their ability to be heated in the AMF in the system
in vitro was shown [8–14].
It has to be noted that mentioned publications have
shown the ability of nanoparticles of perovskite man-
ganite to be heated by AMF action in model experiment
[4, 8, 10, 13–14] and only one study presented theo-
retical calculations of the possibility of effective auto-
stabilization of the temperature in the vicinity of T �C=
42 �C for nanoparticles of perovskite manganite [7].
Unfortunately, studies which could demonstrate the
possibility to heat the tumor tissue with nanoparticles
of perovskite manganite combined with AMF have not
to be found in the accessible literature.
Taking into account this circumstance the current
study was aimed to evaluate the ability of nanopar-
ticles of perovskite manganite, in particular in the
form of magnetic fluid under action of external AMF,
to heat the biological tissues, especially tumor in the
system in vivo.
MATERIALS AND METHODS
Magnetic fluid. Magnetic fluid based on the
synthesized nanoparticles of perovskite manganite
(La1-xSrxMnO3) and water solution of agarose, has been
used in current study. Characteristics of magnetic fluid
were presented earlier [1].
Alternating magnetic field. The rat leg was treat-
ed by external AMF after injection into muscle or in-
tramuscularly transplanted tumor (Guerin carcinoma).
A high frequency generator worked out by Institute
of Electrodynamics was used to induce an alternat-
ing current of 7.7 kA at a frequency of 300 kHz [1].
The current passes through a custom-made five-turn
water-cooled coil of 30 mm in internal diameter and
30 mm in height to generate a magnetic field inside
the coil.
Temperature measurement. Tumor temperature
during heating was measured by means of cooper-
constantan thermocouples (0.1 mm diameter; IF-Kyiv).
The thermocouples were calibrated against a certified
precision mercury-in-glass thermometer (Committee
of State Standards, Ukraine) before and after each
experiment. Temperature was recorded always with
the power switched off.
Animal and tumor models. All studies were con-
ducted with strain IEPOR bread rats (Institute of Experi-
mental Pathology, Oncology and Radiobiology, NAS
of Ukraine, Kyiv, Ukraine) weighting 150–200 g and
Received: September 11, 2012.
*Correspondence: e-mail: osion@onconet.kiev.ua
Abbreviation used: AMF — alternating magnetic field.
Exp Oncol 2012
34, 4, 336–339
Experimental Oncology 34, 336–339, 2012 (December)34, 336–339, 2012 (December) (December) 337
bearing Guerin carcinoma transplanted intramuscu-
larly into the right flank. The principle and method
of transplantation were conventional. Animal were
kept in Makrolon cages bedded with dust-free wood
granulate, and had free access to a standard diet and
tap water. All experiments had been approved by the
regional animal ethics committee.
All 35 female rats were taken into experiment
7–9 days after transplantation (tumor volume
1.0–1.5 cm3), anaesthetized with “calipsovet plus”
at a dose of 0.1 ml/100g b.w., i.p. before the onset
of experiment. Each animal was placed into a special
prepared net-hammock suspended to make free leg.
The net-hammock was fixed on the tripod so that the
femur of animal was localized in the water-cooled mag- of animal was localized in the water-cooled mag-of animal was localized in the water-cooled mag- animal was localized in the water-cooled mag-animal was localized in the water-cooled mag- was localized in the water-cooled mag-was localized in the water-cooled mag- localized in the water-cooled mag-localized in the water-cooled mag- in the water-cooled mag-in the water-cooled mag- the water-cooled mag-the water-cooled mag- water-cooled mag-water-cooled mag-
netic induction coil with diameter of 3.0 cm (Fig. 1).
Suspension of magnetic fluid of manganite perovskite
was administered into the muscle (5 rats) or tumor
(30 rats) at a dose of 0.5–0.6 ml (50 mg manganite
per ml). Tissue temperature was measured when
generator was switched off to avoid the influence
of alternating magnetic field.
Fig. 1. Photograph of rat in the special created net-hammock
(the femur is located in the coil of magnetic field generator)
In experiments in vitro temperature was measured
every 5 min under the switched off generator but
in experiments in vivo such procedure was repeated
not so often to avoid the living tissue damage (every
15–20 min, in average).
RESULTS AND DISCUSSION
It was shown earlier that synthesized nanoparticles
of lanthanum-strontium manganite did not display the
toxicity or provoked the side effects in experimental
animals with transplanted tumors [1].
At the first step of current study it was examined
the ability of magnetic fluid of manganite perovskite
to be heated in model experiment. Magnetic fluid was
taken at a volume of 1.5 ml into the plastic tube which
was located then in the coil of the generator of AMF
in such way the tube setting up in the center of the
field configuration. During the experiment temperature
of magnetic fluid was measured when the generator
was switched off. Obtained results were presented
in Fig. 2. It was registered the increase of magnetic
fluid temperature up to 72–75 �С within 10 min of AMF
action. Fig. 3 represents the plot of temperature versus
time after the onset of AMF action, and clearly dem-
onstrates the increase of magnetic fluid temperature
in comparison with the initial one. It has to be noted
that specimens of magnetic fluid synthesized in diffe-
rent periods of time and used in this study displayed
almost the same changes of temperature under AMF
in experiment in vitro (Fig. 4).
0 5 10 15 20
10
20
30
40
50
60
70
80
t,
°C
min
Fig. 2. Magnetic heating of manganite perovskite magnetic fluid
under applied AMF (300 kHz, 7.7 kA/m). Ordinate — temperature
(Т �С), abscisse — duration of AMF action (min)
0 5 10 15 20
0
1
2
3
4
t/t
0
min
Fig. 3. Plot of temperature (t/t0) versus time of the magnetic
heating of manganite perovskite magnetic fluid under applied
AMF (300 kHz, 7.7 kA/m). Ordinate — temperature (t/t0), ab-
scisse — duration of AMF action (min)
338 Experimental Oncology 34, 336–339, 2012 (December)
0 5 10 15 20 25 30
10
20
30
40
50
60
70
80
t,
°C
min
19.07.12
30.05.12
25.02.12
06.12.11
Fig. 4 Magnetic heating of manganite perovskite magnetic fluid
under applied AMF (300 kHz, 7.7 kA/m). Specimens of magnetic
fluid synthesized in the different period of study were examined.
Ordinate — temperature (Т �С), abscisse — duration of AMF
action (min)
At the second step it was provided the experiments
in vivo. The heating of magnetic fluid was evaluated
after it was injected into the muscle of intact animal
leg or into the tumor in the femur as well as into the
muscle of opposite leg of tumor-bearing rats. It was
determined that the temperature of femur muscle
of intact rat (magnetic fluid was administered into
the muscle) was increased by 8 �С within 20–30 min
of AMF action (Fig. 5). The temperature of tumor (ad-
ministration into the tumor, Guerin carcinoma) was
increased by 8.3 �С within 10 min, by 10.8 �С within
20 min, by 13.6 �С within 30 min of AMF (Fig. 6, 7).
These results have distinctly shown that magnetic fluid
on the basis of lanthanum-strontium manganite is able
to increase the tumor temperature, i.e., “to heat”
the tumor under influence of external AMF and can
be considered as an effective inductor of tumor local
hyperthermia.
0 10 20 30 40
32
34
36
38
40
42
44
46
48
min
t,
°C
Fig. 5. Magnetic heating of rat muscle after intramuscular ad-
ministration of manganite perovskite magnetic fluid under ap-
plied AMF (300 kHz, 7.7 kA/m). Ordinate — temperature (T �С),
abscisse — duration of AMF action (min)
Obtained results are the first demonstration of the
possibility to heat the tumor up to therapeutically
relevant temperature, i.e., 43–44 0 with nanoparticles
of manganite perovskite in the system in vivo. The
temperature in muscle tissue surrounding the tumor
node was not increased over 37–39 �C indicating the
minimal possibility of the normal tissue overheating
(Fig. 8). This observation confirms the idea about the
self-controlled heating by exploitation of manganite
substances [4, 12].
0 5 10 15 20 25 30
28
30
32
34
36
38
40
42
44
46
min
12.12.11
13.12.11(1)
13.12.11(2)
04.11.11
25.01.12
17.04.12
t,
°C
Fig. 6. Magnetic heating of Guerin carcinoma after intratumoral
administration of manganite perovskite magnetic fluid under
applied AMF (300 kHz, 7.7 kA/m). It is given individual curves
of rat tumor heating; experiment on 13.12.11: 1 and 2 — Guerin
carcinoma was transplanted into both femurs of the same rat.
Оrdinate — temperature (T �С), abscisse — duration of AMF
action (min)
0 5 10 15 20 25 30
1,0
1,1
1,2
1,3
1,4
1,5
1,6
min
t/t
0
Fig. 7. Plot of temperature (t/t0) versus time of the magnetic
heating of Guerin carcinoma after intratumoral administration
of manganite perovskite magnetic fluid under applied AMF
(300 kHz, 7.7 kA/m). It is given individual curves of rat tumor
heating. Оrdinate — temperature (t/t0), abscisse — duration
of AMF (min)
It should to be also noted that the analysis of ob- analysis of ob-analysis of ob- of ob-of ob- ob-ob-
tained results has indicated that there is necessity
to discuss the problems of coating, agglomeration
of nanoparticles as well as their size that may influence
the efficacy of heating, the distribution of nanopar- efficacy of heating, the distribution of nanopar-efficacy of heating, the distribution of nanopar- of heating, the distribution of nanopar-of heating, the distribution of nanopar- heating, the distribution of nanopar-heating, the distribution of nanopar-, the distribution of nanopar-the distribution of nanopar- of nanopar-of nanopar-
ticles in the tumor tissue as well as the manifestation
of their magnetic properties in the specific tumor
microenvironment.
The therapeutic relevance of nanohyperthermia
method using manganite perovskite magnetic fluid and
external AMF as single mean as well as in combination
with chemotherapy is under evaluation now in ex-
periment with transplanted tumors in vivo. Moreover,
the advantage of nanohyperthermia in comparison
Experimental Oncology 34, 336–339, 2012 (December)34, 336–339, 2012 (December) (December) 339
with conventional radiofrequency hyperthermia has
to be assessed obligatory, as we suppose.
0 5 10 15 20 25 30
0,95
1,00
1,05
1,10
1,15
1,20
1,25
1,30
1,35
1,40
1,45
1,50
1,55
min
muscle
muscle
tumor
t/t
0
Fig. 8. Plot of temperature (t/t0) versus time of the magnetic
heating of muscle and Guerin carcinoma after intramuscular
or intratumoral administration of manganite perovskite magnetic
fluid under applied AMF (300 kHz, 7.7 kA/m). Ordinate — tem-
perature (t/t0), abscisse — duration of AMF action (min)
ACKNOWLEDGEMENTS
This work was supported by STCU (grant #5213).
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