Journal of Magnetism and Magnetic Materials 340 (2013) 5760

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Journal of Magnetism and Magnetic Materials

journal homepage: www.elsevier.com/locate/jmmm

Preparation and characterization of PVPI-coated Fe3O4 nanoparticles

as an MRI contrast agent
Guangshuo Wang a, Ying Chang b, Ling Wang c,n, Zhiyong Wei b,n, Jianyun Kang d, Lin Sang a,
Xufeng Dong a, Guangyi Chen b, Hong Wang e,n, Min Qi a,n
a
School of Material Science and Engineering, Dalian University of Technology, Dalian 116024,PR China
b
School of Automotive Engineering, State Key Laboratory of Structural Analysis for Industrial Equipment, Dalian University of Technology, Dalian 116024, PR China
c
Department of Oncology, First Afliated Hospital of Dalian Medical University, Dalian116011, PR China
d
Department of Radiology, First Afliated Hospital of Dalian Medical University, Dalian116011, PR China
e
Department of Orthopedics, First Afliated Hospital of Dalian Medical University, Dalian 116011, PR China

articleinfo abstract

Article history: Polyvinylpyrrolidone-iodine (PVPI)-coated Fe3O4 nanoparticles were prepared by using inverse chemical
Received 9 September 2012 co-precipitation method, in which the PVPI serves as a stabilizer and dispersant. The wide angle X -ray
Received in revised form diffraction (WAXD) and selected area electron diffraction (SAED) results showed that the inverse spinel
20 November 2012
structure pure phase polycrystalline Fe 3O4 was obtained. The scanning electron microscopy (SEM) and
Available online 26 March 2013
transmission electron microscopy (TEM) results exhibited that the resulted Fe 3O4 nanoparticles were
Keywords: roughly spherical in shape with narrow size distribution and homogenous shape. Fourier transform
Fe3O4 nanoparticle infrared spectroscopy (FTIR) results suggested that PVPI interacted with Fe 3O4 via its carbonyl groups.
Polyvinylpyrrolidone-iodine Results of superconducting quantum interference device (SQUID) indicated prepared Fe3O4 nanoparticles
Superparamagnetism
exhibited superparamagnetic behavior and high saturation magnetization. T 2-weighted MRI images of
MRI contrast agent
PVPI-coated Fe3O4 nanoparticles showed that the magnetic resonance signal was enhanced signicantly
with increasing nanoparticles concentration in water at room temperature. These results indicated that
the PVPI-coated Fe3O4 nanoparticles had great potential for application in MRI as a T2 contrast agent.
& 2013 Elsevier B.V. All rights reserved.

1. Introduction large specic surface area and strong dipoledipole interaction.

In recent years, magnetic nanoparticles with properties of
superparamagnetism, low toxicity and biocompatibility, have
shown great potential applications in a variety of elds, including
catalysis, biomedicine, magnetic date storage and environmental
remediation [14]. It is well known that Fe 3O4 is the strongest
magnetic nanoparticles of all natural minerals on Earth [5]. During
recent years, one of the fast developing applications of Fe 3O4
nanoparticles is in biomedical areas including magnetic resonance
imaging (MRI) contrast enhancement, targeted drug delivery,
hyperthermia, biological separation, biosensors and diagnostic
medical devices [611]. Especially, a number of studies have been
reported on the application of Fe3O4 nanoparticles as MRI contrast
agent for early cancer diagnosis and treatment [12,13]. To achieve
this aim, Fe3O4 magnetic nanoparticles should have a narrow size
distribution and good dispersibility in aqueous media. However,
pristine magnetic nanoparticles tend to appear aggregation due to
n
Corresponding authors. Tel./fax: +86 411 84706475.
E-mail addresses: whwl2003@tom.com (L. Wang), zywei@dlut.edu.cn (Z. Wei),
whwl@hotmail.com (H. Wang), minqi@dlut.edu.cn (M. Qi).
Thus, a crucial issue inuencing the use of Fe 3O4 nanoparticles for
MRI biological application is the stabilization and functionalization
of their surface. To improve their stabilization, Fe3O4 nanoparticles
have been stabilized with formation of a polymeric layer on the
surface of magnetic nanoparticles, using lipids, proteins, dendri-
mers, gelatin, dextran, chitosan, pullulan, poly(ethyleneglycol)
(PEG), poly(ethylene-co-vinyl acetate), poly(vinylpyrrolidone)
(PVP), or poly(vinyl alcohol) (PVA), etc. [1419].
It has been known that polyvinylpyrrolidone-iodine (PVPI)
complex, commercially named povidone iodine, is water-soluble,
non-toxic and antibacterial, which is often employed in various
medical applications [20,21]. Of particular interest for the present
work is incorporate PVPI into Fe3O4 nanoparticles, which could be
a promising dual-modality for MRI and X-ray imaging due to the
existence of magnetic Fe 3O4 and complexed iodine. In this study,
for the rst time, PVPI-functionalized Fe3O4 nanoparticles were
synthesized and characterized using inverse chemical co-
precipitation method. Then, the structure, morphology and mag-
netic properties of PVPI-coated Fe3O4 nanoparticles were investi-
gated by the wide angle X-ray diffraction (WAXD), Fourier
transform infrared spectroscopy (FTIR), scanning electron micro-
scopy (SEM), transmission electron microscopy (TEM) and

0304-8853/$ - see front matter & 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jmmm.2013.03.023
58 G. Wang et al. / Journal of Magnetism and Magnetic Materials 340 (2013) 5760

superconducting quantum interference device (SQUID). Further-
more, T2-weighted MRI images of PVPI-coated Fe3O4 nanoparticles
were obtained and the results indicated that such surface functio-
nalized Fe3O4 nanoparticles have great potential for application in
MRI as T2 contrast agent.
The mixture was allowed to cool to room temperature. The T2-
weighted images were acquired using spin-echo imaging sequen-
cing with the following parameters: matrix size 320 ~ 320, eld of
view 200 mm ~ 200 mm, slice thickness 2 mm, echo time-
30 ms, repetition time 2000 ms, number of acquisitions 1.

2. Experimental 3. Results and discussion

2.1. Materials The crystalline structure of the Fe3O4 nanoparticles functionalized

with PVPI molecules was characterized by WAXD. As shown in Fig. 1, it
Ferric chloride hexahydrate (FeCl3 6H2O, 98%), ferrous chloride is found that the d-spacing values of signicant peaks match well with
tetrahydrate (FeCl2 4H2O, 98%), ethanol and ammonium hydro- data from the JCPDS card (19-0629) for Fe3O4. The diffraction peaks at
xide (NH4OH, 30%) were purchased from Sinopharm Chemical 2 30.41, 35.71, 43.41, 53.81, 57.21 and 62.91 can be assigned to the
Reagent Co., Ltd. Polyvinylpyrrolidone-iodine (PVPI) was obtained (220), (311), (400), (422), (511) and (440) planes, respectively, which
from Shanghai WellTone Material Technology Co., Ltd (China). All indicates the cubic spinal crystal structure of pure Fe3O4. Moreover, it
chemicals were used directly without further purication. can be clearly seen from Fig. 1 that the diffraction peaks are weaker in
intensity and broader for the Fe3O4 nanoparticles obtained at higher
2.2. Synthesis of PVPI-coated Fe3O4 nanoparticles addition of PVPI. It indicates that the crystallinity decreases for the
modied nanoparticles. The average crystallite size can be estimated
The PVPI-coated Fe3O4 nanoparticles were synthesized by the by WAXD pattern, using the Scherrer Equation [22]:
inverse chemical co-precipitation method according to the follow- k
ing procedure. In a typical experiment, 25 mL 30% ammonia 1
dcos
solution was added to 250 mL three-necked ask. And then
2.352 g of PVPI was dissolved in 100 mL of distilled water contain- where, is the peak-width at half of maximum intensity, k is the shape
ing 2.352 g FeCl3 6H2O and 0.86 g FeCl2 4H2O. The mixture was factor, is the X-ray diffraction wavelength ( 0.154 nm), d is the
stirred for 30 min to obtain a homogeneous solution. The mixture
solution was added dropwise into the ask under vigorous mechan-
ical stirring for 30 min at 25 1C. To prevent oxidative reaction, the
system was kept under nitrogen atmosphere. The resulting solution
was maintained at 80 1C for 1 h and then the solution was cooled to
room temperature. The resulting black precipitate was separated by
a permanent magnet and washed three times with deionized water
and three times with ethanol. The collected magnetic nanoparticles
were dried at 50 1C in vacuum. The prepared Fe 3O4 nanoparticles
with PVPI/FeCl3 6H2O weight ratio of 1/10, 1/1 and 2/1 were
designated as PVPI-Fe3O4-1/10, PVPI-Fe3O4-1/1 and PVPI-Fe3O4-2/
1, respectively.

2.3. Characterization

The wide-angle X-ray diffraction (WAXD) patterns of Fe3O4

nanoparticles were performed on a Dmax-Ultima+X-ray diffract-
ometer (Rigaku, Japan) with Ni-ltered Cu/K- radiation
( 0.15418 nm). The operating target voltage and tube current Fig. 1. WAXD patterns of PVPI (a), Fe3O4 (b), PVPI-Fe3 O4-1/10 (c), PVPI-Fe3O4-1/1
was 40 kV and 100 mA, respectively. The Fourier transform infrared (d) and PVPI-Fe3O4-2/1 (e).
spectroscopy (FTIR) analysis was performed at room temperature
using a Magna 750 spectrometer (Nicolet, USA). The specimen of
Fe3O4 nanoparticles was mixed with KBr pellet and then pressed
into akes for FTIR measurements. Transmission electron micro-
scope (TEM), selected area electron diffraction (SAED) pattern and
high-resolution TEM (HRTEM) were taken on a FEI Tecnai G2 F20
electron microscope. Scanning electron microscopy (SEM) analysis
was obtained on a eld emission SEM microscope (FEI Nanosem
430). The magnetic properties of Fe 3O4 nanoparticles were inves-
tigated in a MPMS-XL-7 superconducting quantum interference
device (SQUID) magnetometer (Quantum Design, USA).

2.4. MR imaging

Magnetic resonance imaging (MRI) tests were performed on a

3.0 T magnetic resonance (MR) scanner (Siemens Magnetom Trio).
PVPI-coated Fe3O4 nanoparticles were dispersed in a 1.5% aqueous
solution of agar with various concentrations and then poured into
tubes (2 mL). Fe3O4 nanoparticles and agar were mixed thoroughly Fig. 2. FTIR spectra of Fe3O4 (a), PVPI-Fe3O4-1/10 (b), PVPI-Fe3O4-1/1 (c), PVPI-
while they were warm by turning the tubes upside down repeatedly. Fe3O4-2/1 (d) and PVPI (e).
 G. Wang et al. / Journal of Magnetism and Magnetic Materials 340 (2013) 5760
average crystallite size, and is the Bragg angle in degree. It should be
noted that the shape factor k is related with several factors, including
the miller index of the reection plane and the shape of the crystal, is
normally 0.89 [23]. The diffraction peak at 35.71 is chosen to calculate
the crystallite size, and the estimated average crystallite size of Fe3O4,
PVPI-Fe3O4-1/10, PVPI-Fe3O4-1/1 and PVPI-Fe3O4-2/1 nanoparticles is
about 16.9 nm, 15.8 nm, 14.2 nm and 12.1 nm, respectively.
The FTIR spectra of PVPI and Fe3O4 nanoparticles coated with
different content of PVPI are shown in Fig. 2. From the IR spectra
presented in Fig. 2a, the peaks at 3441 cm1 and 1630 cm1 are
attributed to the stretching vibrations of OH band and asym-
metric CQO, while the two characteristic absorption bands from
the FeO in Fe3O4 nanoparticles appear at 572 cm1 and 628 cm1.
With the increase of the addition of PVPI, the CQO absorption
bands shifts from 1630 cm1 to 1658 cm1, as shown in Fig. 2ad.
The results show that iron oxide is coordinated through carbonyl
group in PVPI, and the interaction between PVPI and Fe3O4
increases with the decrease of the particle size, which can be
contributed to the surface effect of nanoparticles.
Fig. 3 shows the TEM image (a), SAED pattern (b), SEM image
(c) and HRTEM image (d) of PVPI-Fe3O4-1/1 nanoparticles. As
shown in Fig. 3a, the nanoparticles have average size of 14.9 nm
with narrow size distribution which is in consistent with the
estimation from XRD result (dXRD 14.2 nm). It should be noted
that the obtained Fe 3O4 nanoparticles possess well-dened and
homogenous shape, which can be attributed to the addition of
PVPI acting as stabilizer and dispersing agent. Selected area
electron diffraction pattern reveals that the sample is satisfactory
Fig. 3. TEM image (a), SAED pattern (b), SEM image (c) and HRTEM image (d) of PVPI-Fe3O4-1/1 nanoparticles.
59
polycrystalline of cubic spinal crystal structure, which is in
accordance with the XRD result. SEM image, as shown in Fig. 3c,
presents the morphology of the Fe3O4 nanoparticles is roughly
spherical shape. It has been reported that spherical shape is
formed because the nucleation rate per unit area is isotopic at
the interface between the Fe 3O4 magnetic nanoparticles [24,25].
Fig. 3d shows that the magnetic nanoparticles are structurally
uniform with a lattice fringe spacing about 0.296 nm,
which corresponds to the index of (2 2 0) reections. This value
is in good agreement with the standard data of Fe 3O4 (JCPDS no.
19-0629).
The magnetic properties of PVPI-coated Fe3O4 nanoparticles
were measured out at room temperature using SQUID magnet-
ometer, as shown in Fig. 4. It can be seen that all magnetization
curves appear S-shaped over the applied magnetic eld and the
samples exhibit typical superparamagnetic behavior, showing zero
coercivity, which means that they are attracted by an external
magnetic eld but retain no residual magnetism when the
external magnetic eld is removed at room temperature. The
saturation magnetization (Ms) of the Fe3O4 nanoparticles
decreases from 77.6 emu/g to 53.1 emu/g when PVPI/FeCl3 6H2O
increases from 1/10 to 2/1. This phenomenon indicates that the
Fe3O4 nanoparticles with larger particle size have stronger satura-
tion magnetization. It has been reported that Ms of 722 emu/g is
adoptable for biomedical applications [26,27]. Therefore, the level
of Ms achieved for PVPI-coated Fe3O4 nanoparticles is sufcient for
such applications. A high saturation magnetization (minimum
value is 53.1 emu/g) is preferred for T 2-weighted MRI since the
60 G. Wang et al. / Journal of Magnetism and Magnetic Materials 340 (2013) 5760
Fig. 4. Magnetization curves for Fe 3O4 (a), PVPI-Fe3O4-1/10 (b), PVPI-Fe3O4-1/1
(c) and PVPI-Fe3O4-2/1 (d).
Fig. 5. T2-weighted MRI images (top: grey-scale maps, bottom: color maps) of PVPI-
Fe3O4-1/1 nanoparticles.
spinspin relaxation process of protons in the water molecules
surrounding the nanoparticles is facilitated by a large magnitude
of magnetic spins in nanoparticles.
To determine whether PVPI-coated Fe3O4 nanoparticles could be
used as a contrast agent in MRI, the contrast effect of the as-prepared
PVPI-Fe3O4-1/1 nanoparticles in aqueous solution with different
magnetite concentrations were measured in a clinical 3.0 T MR
system at room temperature. It can be clearly seen from Fig. 5 that
the signal intensity of the MR images is related to the concentration
of Fe3O4 nanoparticles. In color maps, it is clear that as the
concentration of the PVPI-coated Fe3O4 nanoparticles increases, the
image color changes from bright green to blue indicating the gradual
increase of MRI signal intensity. The phenomenon is consistent with
those observations based on the intensity of grey-scale map. The T2
relaxation process occurs because of the exchange of energy between
protons in water molecules. In the presence of an externally applied
magnetic eld, superparamagnetic iron oxide nanoparticles create
inhomogeneity in the magnetic eld affecting the microenvironment
that results in dephasing of the magnetic moments of protons and
hence T2 shortening. Those results indicate that the prepared PVPI-
coated Fe3O4 nanoparticles are promising MRI contrast agent.
4. Conclusion
In summary, the preparation of PVPI-coated Fe3O4 nanoparticles by
the inverse co-precipitation method was reported the present work
and the structure, morphology, magnetization properties and MRI
imaging were examined using different techniques. The average
crystallite and the physical size of the produced nanoparticles were
found to decrease with increasing weight ratio of PVPI to Fe3O4 in the
range between 1/10 and 2/1. The prepared Fe3O4 nanoparticles
exhibited superparamagnetic behavior and high saturation magneti-
zation. MR imaging of the nanoparticles in water conrmed its
contrast enhancement effect in T2-weighted sequences. The results
indicated that the PVPI-coated Fe3O4 nanoparticles could be a promis-
ing T2 contrast agent for MRI.
Acknowledgments
The work was nancially supported by the National Natural
Science Foundation of China (Nos. 31000427, 50901011, 81271719,
81271720) and the Fundamental Research Funds for the Central
Universities (DUT12JB09).
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