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Magnetic Nanoparticle Imaging On the Binding and
Localization of Nanoparticles Using Combination
Magnetic Fields Leslie Nagy, Adam Rauwerdink, Dr.
Guandon Zhang, PI Dr. John Weaver Research
Experience for Undergraduates Program 2008 Center
for Nanomaterials Research _at_ Dartmouth College,
Hanover, NH 03755
Abstract
Discussion/Conclusions
-Preparting particles in gelatin and different
concentrations of glycerol Feridex and
dextran coated magnetite particles were dispersed
in varying concentrations of glycerol and in 4
gelatin. Table 1 shows the method of dispersion
for Feridex in glycerol .
Synthesis and characterization of Fe3O4
nanoparticles was done for the use of measuring
binding in vivo. Characterization by VSM, TEM,
IR, XRD, and SAR showed that magnetic
nanoparticles can be produced and their size,
shape and magnetization can be manipulated in
order to use them in future imaging systems.
These magnetite particles can also be bound to
various biological coatings such as polyethylene
glycol and dextran in order to make the
nanoparticles biocompatible for use in futures
studies in biomedicine such as in imagines
systems and hyperthermia or other various forms
of cancer treatment. In the experiment
involving Feridex the dextran coated
nanoparticles linked to glycerin via hydrogen
bonding. As the hydrogen bonding increased,
molecular motion of the particles decreased so
the ratio of harmonics increased. This is
analogous to the relationship between temperature
and molecular motion. As temperature is
increased, the ratio decreases because molecular
motion is increasing. As the concentration of
glycerin increases, the motion decreases and the
ratio increases. A higher ratio means that there
is less ability to move around and the
sinusoidal wave is more squared off. The more
round the corners, the higher the motion and the
lower the ratio. The higher magnetization of the
particles, the better they can be aligned with
the magnetic field and the higher the ratio.
The ratio is an estimate of mobility. It
allows magnetic nanoparticles to be used as
biomarkers because we have shown that binding, or
increasing or decreasing the mobility of these
particles, impacts the signal given off by the
particles. This study and method is potentially a
way to investigate measuring binding in vivo.
With more investigation, this research has the
ability to tell us if the kinetics of binding are
different, if the particles bind to cancer or
other cells easily, and how fast these particles
will bind to different tissues.
Different magnetite (Fe3O4) nanoparticles were
synthesized and characterized in order to
determine their usefulness in future imaging
systems and biomedical applications.
Characterization was done by VSM, TEM, IR, XRD
and SAR. Synthesized dextran-coated particles
and Feridex were dispersed in various
concentrations of glycerol and were subjected to
an external magnetic field in order to gather
information about how the particles bind and in
order to determine a suitable method to measure
binding in vivo. The higher the mobility of the
particles, the lower the ratio of the 5th
harmonic over the 3rd.
Table I. Amount of Feridex dispersed in various
concentrations of glycerol.
Four samples were prepared using 0.12 g Dextran
coated particle in 5 mL of gelatin and 1 mL of
KOH buffer yeilding a concentration of 5 mg/mL
dextran in 4 gelatin. Measurements of the
samples where then taken using and external
magnetic field.
Figure 6. VSM results for Fe3O4 nanoparticles
after modified by dextran. (Right) shows the
saturation (Ms) and (left) confirms the
coercivity. The saturation of the dextran coated
nanoparticle is 33.68 emu/g and the coercivity is
3.09 Oe.
Introduction
Nanoparticles offer many possibilities in
biomedicine. Because their size can range from a
few nanometers to several micrometers, they are
compatible with biological entities ranging from
proteins to cells and bacteria.1 A material used
in many studies is called magnetite, Fe3O4, which
is a common magnetic iron oxide. With a proper
surface coating, which acts as a glue to keep the
magnetic core together, these magnetic
nanoparticles can be dispersed into suitable
solvents, forming homogeneous suspensions called
ferrofluids.2 Synthesized nanoparticles and
Feridex can be subjected to a magnetic field
that causes the particles to saturate and square
off which means the signal they produce
resembles a square wave. The signal puts off a
nonlinear response which his composed of odd
harmonics. The external magnetic field only
produces a signal at the first harmonic, and the
signals at higher harmonics are only from the
particles. A way to describe the magnetization
of the nanoparticles is by the Langevin function
which shows that the amplitude of the function is
proportional to the drive amplitude (the
amplitude of the external magnetic field) over
the temperature3 (1) as
temperature increases the amplitude decreases. A
calibration curve can be set by changing the
drive field while keeping temperature constant,
so that when the drive field is changed in later
measurements, the current temperature at
different harmonics can be calculated. Informatio
n that is gathered can be used to determine how
binding to different tissues affects the signal.
Potentially if there is cancerous tissue that
these particles can bind to, it would become easy
to know how strongly the particles are bound to
the tissue. Also, there are many upsides to
hyperthermia studies. If the temperature at
different harmonics can be determined then
temperature and binding information could
possibly be gathered in vivo.
Figure 1. The drive coil produces external
magnetic field, the pickup coil picks up and
delivers the signal and the balancing coil
cancels signal from the drive coil, or any signal
not given off by the particles.
-Measuring the signal Synthesized and commercial
particles were put in an external magnetic field
via the instrument shown in Figure I.
Results
4Figure 7. Heating results by SAR . Dextran
coated nano- particles heated up to 37C after 60
seconds while nano- particles containing a
magnetic iron core heated up to 40C after 60
seconds. Measurement conditions Magnetic
field strength was 150 Oe at a frequency of 250
kHz.
Figure 8. TEM image of Fe3O4 coated with dextran
(left) compared to commercial product Feridex
(right). The size of the magnetite particles
coated with dextran is around 15 nm while the
commercial particles are around 8-10 nm.
Figure 2. VSM results of the Fe3O4 nanoparticles
after modified by COOH-PEG-COOH and oleic acid.
(Left) shows the saturation (Ms) of
nanoparticles and (right) confirms their
coercivity values (Hc). The saturation of the PEG
coated nanoparticle is 58 emu/g, compared to 67
emu/g of the untreated Fe3O4 nanoparticles. From
Figure 2, (right) it can be seen that for the PEG
and oleic acid modified nanoparticles, there is
no hysteresis, and both remanence and coercivity
are zero, suggesting they are superparamagnetic.
The untreated Fe3O4 nanoparticle has a small
coercivity around 6 Oe.
Figure 3. TEM images of Fe3O4 nanoparticles after
modified by COOH-PEG-COOH (left) and oleic acid
(right). The Fe3O4 nanoparticles coated with PEG
have a round shape, and the size is around 7 nm
with a narrow distribution
Future Studies
Along with phase change experiments, we are also
interested in binding a lectin called
Concanavalin A to the dextran in Feridex to see
the differences in signal when the particles are
bound with a relatively weak covalent linkage
that bind onto the dextran sugar moieties
noncovalently.
References
Figure 4. IR results of the PEG coated
Fe3O4 superparamagnetic nanoparticle. .
Absorption bands at 2930 and 2850 cm-1 are
related to CH2 group in the PEG structure 1050
cm-1 is due to C-O bond stretching 3420 cm-1 is
from -OH group 585 cm-1 is Fe-O bond vibration
in Fe3O4 structure. The peaks at 1490 and 1390
cm-1 are due to the COO-. Fe3O4 nanoparticle
functioned with the COOH group has the ability
to react with NH2 group on the biological
tissues or the other compounds forming the
covalent bond via EDC reaction.
1 Pankhurst, Q. A. et al J. Phys. D Appl. Phys.
2003. Vol 36 R167-R181 2 Gupta, A. K., Gupta, M.
Biomaterials. 2005. Vol 26, 3995-4021 3 Gleich,
B., Weizenecker, J. Nature. 2005. Vol 435,
1214-1217 4 A. Huey REU presentation July 2008
Figure 9. Ratio of the 5th and 3rd harmonics vs.
percent glycerin at 244 Hz and 6160 Hz. At 244
Hz, as the concentration of glyercin increases,
the ratio of the harmonics increases. At 6160
Hz, as the concentration of glycerin increases,
the ratio of harmonics remains the same. Ratio
of harmonics does not change because the
strength of the magnetic field at this frequency
does not line up with the magnetic saturation of
the magnetic nanoparticles.
Acknowledgments
Experimental
Figure 5. XRD spectrum of Fe3O4 coated with PEG.
Core-shell iron has a-Fe core surrounded by a 2
3 nm-thick oxide layer with a disordered cubic
spinel structure. In the shell, two different
iron oxides, magnetite (Fe3O4) and maghemite (? -
Fe2O3), share this lattice structure, with Fe3O4,
a8.3967A, and ?-Fe2O3, a8.346A. The stability
of the Fe nanoparticle depends on the particle
size and surface situation. After long time
dispersed in water based solution, the Fe
particles with different coatings are possible to
covert into different products. XRD is effective
to tell these compounds, such as Fe, Fe3O4, ?-
Fe2O3 and FeOOH.
-Synthesizing the partcicles Magnetite
nanoparticles coated with polyethylene glycol and
dextran were synthesized by means of a
co-precipitation method. The concentration of the
iron salt solutions were controlled in order to
manage the size and distribution of the
particles. Characterization was done using
transmission electron microscope (TEM), x-ray
diffraction (XRD), infrared spectroscopy (IR),
vibrating sample spectrometer (VSM) and specific
absorption rate (SAR).
I would like to thank Dr. John Weaver, Dr.
Guandong Zhang, Adam Rauwerdink, Amanda Huey and
Dartmouth Staff. This program was funded by
the NSF Research Program for Undergraduates
Figure 10. Possible future studies. Results of
3rd and 5th harmonics and the ratio of the
5th/3rd vs. time in seconds. As frozen iron
oxide particles experience a phase change at a
constant temperature, the signal increases. As
temperature starts increasing, however, the
effects of thermal energy causes the signal to
decrease with time. Because the particles are
moving more because of thermal energy rather than
because of the field, the signal decreases as
described by the Langevin Theory.