A method of non-invasive localization of magnetic nanoparticles injected in living animal is presented. Measuring the magnetic response of magnetic nanoparticles to AC magnetic field by using SQUID biosusceptometric system is investigated. Experimental measurements in vivo and in vitro show possibility of using this method as a non-invasive method of identification and distribution of magnetic nanoparticles in biological tissues of small animals.
Keywords: magnetic nanoparticles, SQUID, superparamagnetism, experimental animal
In recent years the use of magnetic nanoparticles in
medicine has been risen. There are attempts to use
them in cancer diagnostics, direct treatment like
hyperthermia or the use of nanoparticles for targeted
drug delivery. Magnetic nanoparticles (MNP) with
appropriate properties, which are focused to the treated
organ by external magnetic field, seem to be very
useful carriers for various genes [1, 2, 3]. For
biocompatibility these MNP should be covered by
appropriate polymers, such as polyetylenglycol,
polyetylenimin, heparin. The covering, shape and size
of MNP is crucial from the view of transport properties
in the cells and their toxicity. Unsuitable MNP may
cause inflammatory reaction in various organs and
Determination of the distribution of MNP in living
organism is the first important issue to confirm the
effects of magnetic nanoparticles and also to evaluate
the possible untoward effects. In this study, SQUID
biosusceptometric system (SBS) was used for magnetic
nanoparticle detection test, performed by in and ex vivo
scanning of Wistar rats to clarify the distribution of
MNP in living organism for the pharmacokinetics
analysis, like drug delivers.
SBS consists of the RF SQUID, 2nd-order
gradiometer, electronic modules, movable bed and the
magnetization system with Helmholtz coils generating
the magnetic field in the direction of gradiometer axis.
AC magnetic field has the intensity of 240 A/m and the
frequency of 2.8 Hz.
This frequency enables to achieve a low level of the
disturbing signal, as the most significant disturbing
components are the fluctuations of the DC geomagnetic
field component and the low-frequency band
components below ~ 1 Hz, and also enables to
minimize the effects of eddy currents (induced in the
walls of the shielded chamber - Faraday cage)
influence. The gradiometer sensor is placed close
(~1 cm) to the surface of measured object. The spectral
sensitivity of the measuring system (for the
gradiometer pickup coil with the diameter of
2.8×10- 2 m) is ~ 2×10-14 T Hz-1/2.
Magnetometric measurement of MNP solution was
performed with the same SQUID gradiometric system,
by using different magnetization system and
compensation coil .
Studied Fe3O4 nanoparticles were prepared by
microemulsion method at Polymer Institute of SAS by
prof. Ignác Capek. These superparamagnetic Fe3O4
MNP were coated with citric acid and the mean
hydrodynamic particle diameter was ~ 35 nm. From the
magnetization measurement, fig. 1, the mass magnetic
susceptibility was determined, which was later used to
determine the concentration of this MNP in the organs
of the tested animal.
Fig. 2 documents the measured values of the output
signal Upp, depending on the distance d of the
cylindrical surface of the model, where cF is the
concentration of MNP in the water filled model.
i) From the characteristics is clear that the active area
of the measured object is located near the surface.
The level of the magnetic signal decreases with
a ratio of approximately 1/d3, so it can be assumed that
the effective detection of MNP will be in ∼ 5 cm depth.
Sensing characteristic of the 2nd-order gradiometer is
narrow, so effective detection field has a shape of cone
with a base diameter of 5 cm and a height of 5 cm. On
the other side, this narrow sensing characteristics
allows better determining of different cF in various
locations of the measured object.
ii) Living biological tissue is diamagnetic and this is
presented on figures with negative values of output
signal Upp. This means that at low values of cF, the
measured object still will appear as diamagnetic.
Specifically, for our SBS and the object with used
35 nm MNP solution, the transition from paramagnetic
to diamagnetic state is expected when the value of cF is
in the range 13 - 20 μgFe3O4 cm-3. Relationship Upp and
cF is influenced mainly by contribution of diamagnetic
biological tissues, which in terms of susceptibility
appears to be water, paramagnetic MNP and also
paramagnetic air layer between the sensor and the
surface of the measured object.
Results of measurements of Upp in experimental
animal, which was injected to tail with 1 cm3 solution
of MNP and after 5 minutes measured, could be seen in
Measured Upp values clearly show the difference
between the magnetic response before and after
injection of the MNP solution. Plotted values of Upp
correspond to cF obtained during movement of the
animal under the SQUID sensor along the torso (left
part) and upper part of the tail (right side). From the
measured values, the accumulation of MNP in the
region of heart and liver could be assumed.
Subsequently, the animals were sacrificed and
selected organs were removed to be measured with the
SBS. Obtained data were used to determine the
magnetic susceptibility of tissues, or cF of MNP in the
tissue. From the results shown in fig. 5, MNP are
mostly accumulated in the liver.
In the paper SBS and the method for measurement
of magnetic response of Fe3O4 MNP to the AC
magnetic field in the samples and also of injected MNP to tissues of the living animal are presented.
Dependences between measured output signal, the
concentration and distance of the sensor from
magnetized MNP were obtained. Experimental
measurements on living rat showed a possibility of
using this method as an non-invasive method of
identification and distribution determination of MNP in
biological tissues of small animals. It can be assumed
that by focusation of MNP with the external magnetic
field, MNP could be accumulated in other areas of the
This work was supported by Agency of the Ministry
of Education of the Slovak Republic for the Structural
Funds of the EU, Operational Programme Research
and Development (OPVaV-2009/4.1/02-SORO),
Project Code 26240120019 (0.7) and by VEGA grant
Mgr. Martin Škrátek, PhD.
Institute of Measurement Science
Slovak Academy of Sciences
Dúbravská cesta 9, SK-841 04 Bratislava
Phone: +421 259 104 528
Fax: +421 254 775 943
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