Colloids and Surfaces A: Physicochem. Eng.

Aspects 375 (2011) 163168

Contents lists available at ScienceDirect

Colloids and Surfaces A: Physicochemical and

Engineering Aspects
journal homepage: www.elsevier.com/locate/colsurfa

Fabrication of functional block copolymer grafted superparamagnetic

nanoparticles for targeted and controlled drug delivery
Bin Mu a , Tingmei Wang b , Zhenhua Wu a , Huigang Shi c , Desheng Xue c , Peng Liu a,
a
Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province and Institute of Polymer Science and Engineering,
College of Chemistry and Chemical Engineering, Lanzhou University, Tianshui Road 298#, Lanzhou 730000, Gansu, China
b
State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China
c
Key Laboratory for Magnetism and Magnetic Materials of the Ministry of Education, Lanzhou University, Gansu 73000, China

a r t i c l e i n f o a b s t r a c t

Article history: The functional block copolymer (poly(hydroyethyl acrylate-b-N-isopropylacrylamide), P(HEA-b-

Received 4 September 2010 NIPAm)) grafted Fe3 O4 nanoparticles (Fe3 O4 @P(HEA-b-NIPAm)) with temperature-responsive poly(N-
Received in revised form isopropylacrylamide) (PNIPAm) as the skin layer were designed via the consecutive surface-initiated
25 November 2010
atom transfer radical polymerization (SI-ATRP) from the surfaces of the superparamagnetic Fe3 O4
Accepted 26 November 2010
nanoparticles. The targeted functional and temperature-sensitive nanoparticles were characterized by
Available online 9 December 2010
the FT-IR, XPS, TEM, VSM, and DLS techniques. It is expected that the multi-functional nanoparticles could
be used for the targeted and controlled drug delivery.
Keywords:
Superparamagnetic nanoparticle 2010 Elsevier B.V. All rights reserved.
Block copolymer
Environmental responsive
Surface-initiated atom transfer radical
polymerization
Drug delivery

1. Introduction methods, the grafting from approach via the surface-initiated

In the last decades, more and more investigations with sev-
eral types of iron oxides have been carried out in the eld of
nanosized magnetic particles (mostly maghemite, -Fe2 O3 or mag-
netite, Fe3 O4 single domains of about 520 nm in diameter), among
which magnetite is the most promising candidate since its biocom-
patibility has already been proved [1]. Although these magnetic
nanoparticles have been successfully used as magnetic resonance
imaging (MRI) contrast agents and in hyperthermic treatment for
cancer cells [24], their application in targeted and controlled drug
delivery has been limited because that the pristine iron oxide mag-
netic nanoparticles cannot be loaded with drugs. Therefore, the
incorporation of magnetic nanoparticles with polymers has been
developed to increase their biocompatibility and ability to realize
the controlled delivery for pharmaceuticals.
Several methods, such as physical adsorption of polymers [5],
dispersion or emulsion polymerization in the presence of the mag-
netite nanoparticles [68], and the so-called grafting to and
grafting from methods [911], have been developed to prepare
polymer-coatings on the magnetite nanoparticles. Among these
Corresponding author. Tel.: +86 931 8912516; fax: +86 931 8912582.
E-mail address: pliu@lzu.edu.cn (P. Liu).
atom transfer radical polymerization (SI-ATRP) has been proved to
be the most potential method because that it does not require strin-
gent experimental conditions and allows the direct polymerization
of the functional monomers without involving the tedious protec-
tion and deprotection procedures in a controlled fashion, yielding
polymers with narrowly dispersed molecular weights [1214]. By
far, there is little work on the block copolymers grafted magnetic
nanoparticles via the SI-ATRP approach.
Aimed at the targeted and controlled release of drugs, the
crosslinked thermo-responsive polymer shells have been coated
onto the magnetic nanoparticles via the SI-ATRP technique [15,16].
In the present work, the block copolymer (poly(hydroyethyl
acrylate-b-N-isopropylacrylamide), P(HEA-b-NIPAm)) has been
grafted from the surfaces of the superparamagnetic Fe3 O4
nanoparticles with the poly(N-isopropylacrylamide) (PNIPAm)
skin layer via the consecutive SI-ATRP of hydroyethyl acry-
late (HEA) and N-isopropylacrylamide (NIPAm) after the Fe3 O4
nanoparticles were surface-modied with -bromoisobutyric acid
(BIBA) (Scheme 1). The products, functional superparamagnetic
Fe3 O4 @P(HEA-b-NIPAm) nanoparticles, were characterized with
Fourier transform infrared (FT-IR), X-ray photoelectron spectrom-
eter (XPS), transmission electron microscope (TEM), vibrating
sample magnetometer (VSM), and dynamic light scattering (DLS)
techniques.

0927-7757/$ see front matter 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.colsurfa.2010.11.081
164 B. Mu et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 375 (2011) 163168
Scheme 1. Schematic illustration of the route to the functional superparamagnetic nanoparticles Fe3 O4 @P(HEA-b-NIPAm).
2. Experimental
2.1. Materials
Ferric chloride hexa-hydrate (FeCl3 6H2 O), ferrous chloride
tetra-hydrate (FeCl2 4H2 O), ammonia solution (NH3 H2 O, 25% of
ammonia), -bromoisobutyric acid (BIBA), and isopropyl alcohol
were analytical grade reagents received from Tianjin Chemi-
cal Co. (Tianjin, China) and used without further purication.
Hydroethyl acrylate (HEA) is analytical reagent grade from Bei-
jing Eastern Yakeli Chemical Engineering S & T Ltd., Co., Beijing,
China. N-isopropylacrylamide (NIPAm) and N,N,N ,N ,N -penta-
methyldiethylenetriamine (PMDTA) were purchased from Aldrich.
Cu(I)Br (Tianjin Chemical Co., Tianjin, China) was puried by stir-
ring in glacial acetic acid, ltered, washed with ethanol and dried.
2.2. Initiator-modied Fe3 O4 nanoparticles
The co-precipitation method was used to prepare the Fe3 O4
nanoparticles [17]: FeCl3 6H2 O (13.0 g) and FeCl2 4H2 O (4.8 g) in
a 1:2 molar ratio were dissolved in distilled water (200 mL) under
nitrogen atmosphere with vigorous stirring. As the solution was
heated to 70 C, NH3 H2 O (28 wt%, 25 mL) was added dropwise to
the solution under vigorous stirring and the reaction was allowed
to proceed for 5 h at 70 C, and then the temperature was increased
to 85 C to vapor the residual NH3 .
Then 100 mL aqueous solution of -bromoisobutyric acid (BIBA)
(0.048 mol (8 g)) was dropped into the dispersion of the Fe3 O4
nanoparticles and the pH value of the dispersion was controlled to
be about 4.0 in the procedure. After the mixture was stirred for 24 h,
the ultimate initiator-modied Fe3 O4 nanoparticles (Fe3 O4 Br)
were washed with distilled water to neutral to discard the excessive
-bromoisobutyric acid by the magnetic separation procedure.
2.3. Consecutive SI-ATRP
The initiator-modied Fe3 O4 nanoparticles (Fe3 O4 Br),
3.0 mmol CuBr, 6.0 mmol PMDTA and 15.0 mL HEA were dis-
persed ultrasonically into 80 mL water. The dispersion was heated
at 60 C for 48 h. The products, Fe3 O4 @PHEA, were washed with
ethanol/water and dried under vacuum.
The Fe3 O4 @PHEA nanoparticles, 3.0 mmol CuBr, 6.0 mmol
PMDTA and 100.0 mmol NIPAm were dispersed ultrasonically into
80 mL isopropyl alcohol. The mixture was heated at 60 C for
60 h. The products, Fe3 O4 @P(HEA-b-NIPAm), were washed with
ethanol/water and dried under vacuum.
2.4. Characterizations
Bruker IFS 66 v/s infrared spectrometer (Bruker, Karlsruhe,
Germany) was used for the Fourier transform infrared (FTIR)
spectroscopy analysis in the range of 4004000 cm1 with the res-
 B. Mu et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 375 (2011) 163168 165

80000 Fe 2p1/2 100

Fe 2p3/2
70000
Fe3O4@P(HEA-b-NIPAm)
1
O 1s
60000 90
2
-1
50000
C 1s 2930, 2867 cm
N 1s

Transmittance (%)
Br 3d 3
-1
O-C=O, 1721 cm
c/s

40000 80
4
30000
Fe3O4@PHEA -1
70 -1 N-C=O, 1651 cm
20000 -OH, -NH, 3400 cm

10000 Fe3O4-Br
1 Fe3O4
60 2 Fe3O4-Br -1
0 Fe-O, 590 cm
0 200 400 600 800 1000 3 Fe3O4@PHEA
4 Fe3O4@P(HEA-b-NIPAm)
Binding energy (eV)
50
Fig. 1. XPS survey spectra of the Fe3 O4 Br, Fe3 O4 @PHEA, and Fe3 O4 @P(HEA-b- 4000 3500 3000 2500 2000 1500 1000 500
NIPAm) nanoparticles. -1
Wavenumber (cm )

Fig. 2. FTIR spectra of the Fe3 O4 , Fe3 O4 Br, Fe3 O4 @PHEA, and Fe3 O4 @P(HEA-b-
olution of 4 cm1 . The KBr pellet technique was adopted to prepare NIPAm) nanoparticles.
the sample for recording the IR spectra.
The surface characterization of the samples was accomplished
using a PHI-5702 multi-functional X-ray photoelectron spectrome-
ter (XPS) with pass energy of 29.35 eV and an Mg K line excitation 100
source. The binding energy of C 1s (284.6 eV) was used as a refer-
ence. 98
The morphologies of the nanoparticles were characterized with
a JEM-1200 EX/S transmission electron microscope (TEM) (JEOL, 96
Tokyo, Japan). They were dispersed in water in an ultrasonic bath
for 5 min, and then deposited on a copper grid covered with a per-
Weight (%)

94
forated carbon lm.
Magnetic properties of the Fe3 O4 nanoparticles were detected 92
by vibrating sample magnetometer (VSM) (Lakeshore 7304).
The mean particle size and size distributions of the nanoparticles 90
were determined by the dynamical mode (dynamic light scatter- Fe3O4-Br
ing (DLS)) on the Light Scattering System BI-200SM, Brookhaven 88 Fe3O4@PHEA
Instruments device equipped with the BI-200SM goniometer, the
Fe3O4@P(HEA-b-NIPAm)
BI-9000AT correlator, temperature controller and the Coherent 86
INOVA 70C argon-ion laser at 20 C. DLS measurements are per- 100 200 300 400 500 600 700 800
formed using 135 mW intense laser excitation at 514.5 nm and at Temperature (C)
a detection angle of 90 using the emulsion directly at 25 C. Parti-
cle size distribution is calculated using the Brookhaven Instruments Fig. 3. TGA curves of the Fe3 O4 Br, Fe3 O4 @PHEA, and Fe3 O4 @P(HEA-b-PNIPAm)
Particle sizing software. The details of the laser light scattering (LLS) nanoparticles.

instrumentation and theory can be found in the literature [18].

3. Results and discussion

Fe3O4

In the present work, -bromoisobutyric acid was adsorbed onto 60 Fe3O4@PHEA

the surfaces of the Fe3 O4 nanoparticles via the electrostatic inter- Fe3O4@P(HEA-b-NIPAm)
actions to be used as the initiators for the consecutive SI-ATRP of 40
hydroyethyl acrylate (HEA) and N-isopropylacrylamide (NIPAm)
Magnetization (emu/g)

[17,19]. After the surface modication, the Br 3d binding peak was 20

found in the XPS survey spectrum (Fig. 1) of the modied nanoparti-
0
cles (Fe3 O4 Br) with a surface elemental content of 1.24% (Table 1).
It indicated that -bromoisobutyric acid had been immobilized
-20
onto the surfaces of the Fe3 O4 nanoparticles.
-40
Table 1
The surface compositional data from XPS. -60
Samples XPS analysis (at.%)

Fe O Br C N -10000 -5000 0 5000 10000

Magnetic field (Oe)
Fe3 O4 Br 21.29 29.17 1.24 48.30
Fe3 O4 @PHEA 19.11 28.60 0.85 51.44
Fig. 4. Magnetization curves of the Fe3 O4 , Fe3 O4 @PHEA, and Fe3 O4 @P(HEA-b-
Fe3 O4 @P(HEA-b-NIPAm) 11.73 26.86 0.59 58.38 2.42
NIPAm) nanoparticles.
166 B. Mu et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 375 (2011) 163168

After the SI-ATRP, the surface elemental content of Fe, O,
and Br decreased while that of C increased in the products via
the consecutive SI-ATRP of hydroyethyl acrylate (HEA) and N-
isopropylacrylamide (NIPAm). The N 1s binding peak appeared in
the XPS survey spectrum (Fig. 1) of the nanoparticles after the sec-
ond step of SI-ATRP. It showed that the poly(hydroyethyl acrylate)
(PHEA) and the block copolymer (poly(hydroyethyl acrylate-b-
N-isopropylacrylamide), P(HEA-b-NIPAm)) has been successfully
grafted from the surfaces of the Fe3 O4 nanoparticles.
Fig. 2 shows the FTIR spectra of the Fe3 O4 , Fe3 O4 Br,
Fe3 O4 @PHEA, and Fe3 O4 @P(HEA-b-PNIPAm) nanoparticles. The
FTIR spectrum of the Fe3 O4 @PHEA nanoparticles reveals that
the typical stretching vibration absorbance peaks of ester
groups appeared at about 1721 cm1 which further indicated
that the poly(hydroxyethyl acrylate) (PEA) was successfully
grafted from the surface of the magnetic nanoparticles. Fur-
thermore, the stretching vibration of hydroxyl groups was also
indicated at around 3400 cm1 . The well-dened stretching vibra-
tion absorbance peaks of carbonyl of ester groups at around
1721 cm1 and amide group at 1651 cm1 were found in the
FTIR spectrum of the nal products, the poly(hydroxyethyl
acrylate-b-N-isopropylacrylamide) grafted Fe3 O4 nanoparticles
(Fe3 O4 @P(HEA-b-PNIPAm)) (Fig. 2).
The TGA curves of the Fe3 O4 Br, Fe3 O4 @PHEA, and
Fe3 O4 @P(HEA-b-PNIPAm) nanoparticles were shown in Fig. 3.
According to the TGA results, the percentage of grafting (PG, mass
ratio of the grafted polymer to the magnetic nanoparticles) could
be calculated to be 10.5% and 15.0% for the Fe3 O4 @PHEA and
Fe3 O4 @P(HEA-b-PNIPAm) nanoparticles, respectively. And the
grafting density of the PHEA and the P(HEA-b-PNIPAm) has been
found to be about 780 and 1090 mol/m2 , respectively [20,21].
The hysteresis curves of the Fe3 O4 nanoparticles, Fe3 O4 @PHEA
nanoparticles, and Fe3 O4 @P(HEA-b-NIPAm) nanoparticles were
illustrated in Fig. 4. Neither the remanence nor the coercivity was

Fig. 5. TEM images of the Fe3 O4 , Fe3 O4 @PHEA, and Fe3 O4 @P(HEA-b-NIPAm) nanoparticles.
 B. Mu et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 375 (2011) 163168 167

observed in the three hysteresis curves. They exhibited super- 120 30

paramagnetic with the saturation magnetization (Ms) values of
68.23, 63.58, and 55.22 emu/g at 25 C, respectively. It indicated 100
that the polymerization did not affect the magnetic properties of 25

Scattered Intensity
the superparamagnetic nanoparticles because that the structure of
80
the Fe3 O4 nanoparticles was remained in the polymerization proce-

<Dh> (nm)
dure. Furthermore, the decrease in the saturation magnetization of
20
the Fe3 O4 @PHEA and Fe3 O4 @P(HEA-b-NIPAm) nanoparticles com- 60
pared with the Fe3 O4 nanoparticles was ascribed to the PHEA and
PNIPAm ingredients grafted. 40 15
There is no evident change of the Fe 2p1/2 and Fe 2p3/2 binding
peaks found in the XPS spectra of the modied Fe3 O4 nanoparticles
[22]. So the percentage of grafting (dened as the mass ratio of the 20
(co)polymer grafted and the magnetic nanoparticles) could be cal- 10
culated to be about 7% for the Fe3 O4 @PHEA nanoparticles and 19% 25 30 35 40 45
o
for the Fe3 O4 @P(HEA-b-NIPAm) nanoparticles from the changes of Temperature ( C)
their saturation magnetization (Ms) values, which was near to the
Fig. 7. Temperature dependence of average hydrodynamic diameter (Dh ) of the
results of TGA. The low percentage of grafting might be due to the Fe3 O4 @P(HEA-b-NIPAm) nanoparticles.
low content of the initiating groups in the initiator-modied Fe3 O4
nanoparticles (Fe3 O4 Br) resulted from their small particle size of
tion took place around 32 C. It indicated that the PHEA block had
about 10 nm (Fig. 5).
no inuence on the temperature responsive characteristics of the
The preparation procedure of the Fe3 O4 @P(HEA-b-NIPAm)
PNIPAm block in the copolymers. Furthermore, the scattered light
nanoparticles was also tracked with the dynamic light scattering
intensity decreased with the increasing of the environmental tem-
(DLS) technique (Fig. 6). The average hydrodynamic diameters (Dh )
perature. It might be due to the shrinking of the block copolymers
of the Fe3 O4 , Fe3 O4 @PHEA, and Fe3 O4 @P(HEA-b-NIPAm) nanopar-
at the higher temperature.
ticles were found to be 70.9 nm, 70.0 nm, and 72.4 nm, respectively.
Moreover, the typical hydrodynamic diameter distribution,
The average hydrodynamic diameters were much bigger than that
f(Dh), of the Fe3 O4 @P(HEA-b-NIPAm) nanoparticles at 27, 31, 33,
determined by the TEM technique of about 10 nm. It might be due
and 45 C are shown in Fig. 8, which illustrates that the size distribu-
to the association and aggregation of the Fe3 O4 nanoparticles in
tions are monodisperse without apparent aggregation between the
water via the van der Waals forces and/or hydrogen bond.
nanoparticles in the course of the increasing temperature, and all
It is well-known that the PNIPAm homopolymer experiences
the size distributions gradually become narrow with the increasing
a coil-to-globule phase transition in dilute aqueous solution at
temperature.
its lower critical solution temperature (LCST) about 32 C [23].
The photographs of the aqueous dispersions of the
The PNIPAm chains carry out a random-coil conformation at
Fe3 O4 @P(HEA-b-NIPAm) nanoparticles are given in Fig. 9(a),
temperatures below 32 C, on the contrary, the intramolecular
that was well dispersed in water under normal conditions. On the
hydrogen-bonding interactions between C O and NH groups help
contrary, the nanoparticles rapidly gathered on the sidewall of the
the polymer chains to collapse and compact at above its LCST due
colorimetric cylinder under a magnetic approach (Fig. 9(b)). This
to the reducing of their water solubility. The temperature respon-
result indicated that the Fe3 O4 @P(HEA-b-NIPAm) nanoparticles
sive characteristics of the Fe3 O4 @P(HEA-b-NIPAm) nanoparticles
can be easily manipulated by an external magnetic eld.
were characterized with dynamic light scattering (DLS) in aque-
The inner PHEA blocks (or other polymers as being designed)
ous solutions by investigating the change of their particles size in
could be the drug storage via the van der Waals forces and/or
aqueous solution at different temperatures. Fig. 7 shows the tem-
hydrogen bond between its functional side groups and the drug
perature dependence of the average hydrodynamic diameter (Dh )
molecules. And the skin PNIPAm blocks could act as the switch
of the Fe3 O4 @P(HEA-b-NIPAm) nanoparticles. As can be seen from
to control the release of the drug encapsulated in answer to
Fig. 7, the coil-to-globule phase transition in dilute aqueous solu-

120

110 Fe3O4 o
45 C
Fe3O4@PHEA
100
Fe3O4@P(HEA-b-NIPAm) o
33 C 31 C
o o
88 27 C
80

66
60
f(Dh)
f(Dh )

44 40

22 20

0 0
60 65 70 75 80 20 40 60 80 100 120
Dh(nm) <Dh>/nm

Fig. 6. Hydrodynamic diameter Dh and size distribution f(Dh) of the Fe3 O4 , Fig. 8. Hydrodynamic diameter Dh and size distribution f(Dh) of the Fe3 O4 @P(HEA-
Fe3 O4 @PHEA, and Fe3 O4 @P(HEA-b-NIPAm) nanoparticles. b-NIPAm) nanoparticles at different temperatures.
168 B. Mu et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 375 (2011) 163168
Fig. 9. Photographic images of the Fe3 O4 @P(HEA-b-NIPAm) nanoparticles.
the temperature changes. Therefore, the Fe3 O4 @P(HEA-b-NIPAm)
nanoparticles with targeted function and temperature-sensitivity
have signicant potential for wide applications in the medical eld,
such as drug delivery vehicles.
4. Conclusions
The magnetic-targeted and temperature-sensitive nanoparti-
cles, block copolymer poly(hydroyethyl acrylate-b-N-isopropyl-
acrylamide) grafted Fe3 O4 nanoparticles P(HEA-b-NIPAm)
(Fe3 O4 @P(HEA-b-NIPAm)) were designed for the potential
application in the targeted and controlled drug delivery. Their
Fe3 O4 nanoparticle cores possess the targeted function. The inner
PHEA blocks (or other polymers as being designed) could improve
the loading capacity of drugs. And the temperature responsive skin
PNIPAm blocks could act as the switch to control the release of the
drug encapsulated.
Acknowledgments
This Project was granted nancial support from the National
Nature Science Foundation of China(Grant No. 20904017), Pro-
gram for New Century Excellent Talents in University (Grant No.
NCET-09-0441), and the National Science Foundation for Fostering
Talents in Basic Research of the National Natural Science Founda-
tion of China (Grant No. J0730425).
References
[1] U. Schwertmann, R.M. Cornell, Iron Oxides in the Laboratory: Preparation and
Characterization, VCH, Cambridge, Weinheim, 1991.
[2] A.H. Lu, E.L. Salabas, F. Schuth, Magnetic nanoparticles: synthetic, protection,
functionalization and applications, Angew. Chem. Int. Ed. 46 (2007) 12221244.
[3] Y. Wang, Y.W. Ng, Y. Chen, B. Shuter, J.B. Yi, J. Ding, S.C. Wang, S.S. Feng,
Formulation of superparamagnetic iron oxides by nanoparticles of biodegrad-
able polymers for magnetic resonance imaging, Adv. Funct. Mater. 18 (2008)
308318.
[4] R.R. Qiao, C.H. Yang, M.Y. Gao, Superparamagnetic iron oxide nanoparticles:
from preparations to in vivo MRI applications, J. Mater. Chem. 19 (2009)
62746293.
[5] D.N. Williams, K.A. Gold, T.R.P. Holoman, S.H. Ehrman, O.C. Wilson Jr., Surface
modication of magnetic nanoparticles using gum Arabic, J. Nanopart. Res. 8
(2006) 749753.
[6] J.J. Huang, H. Pen, Z.S. Xu, C.F. Yi, Magnetic Fe3 O4 /poly(styrene-co-acrylamide)
composite nanoparticles prepared by microwave-assisted emulsion polymer-
ization, React. Funct. Polym. 68 (2008) 332339.
[7] L.H. Fan, Y.L. Luo, Y.S. Chen, C.H. Zhang, Q.B. Wei, Preparation and characteriza-
tion of Fe3 O4 magnetic composite microspheres covered by a P(MAH-co-MAA)
copolymer, J. Nanopart. Res. 11 (2009) 449458.
[8] C. Paquet, L. Page, A. Kell, B. Simard, Nanobeads highly loaded with super-
paramagnetic nanoparticles prepared by emulsication and seeded-emulsion
polymerization, Langmuir 26 (2010) 53885396.
[9] C. Flesch, E. Bourgeat-Lami, S. Mornet, E. Duguet, C. Delaite, P. Dumas,
Synthesis of colloidal superparamagnetic nanocomposites by grafting
poly(-caprolactone) from the surface of organosilane-modied maghemite
nanoparticles, J. Polym. Sci. Part A: Polym. Chem. 43 (2005) 32213231.
[10] S.X. Wang, Y. Zhou, W. Guan, B.J. Ding, Preparation and characterization of smart
polymer brush-modied magnetic nanoparticles for biomedicine application,
J. Nanopart. Res. 11 (2009) 909916.
[11] Z.P. Xiao, K.M. Yang, H. Liang, J. Lu, Synthesis of magnetic, reactive, and
thermoresponsive Fe3 O4 nanoparticles via surface-initiated RAFT copolymer-
ization of N-isopropylacrylamide and acrolein, J. Polym. Sci. Part A: Polym.
Chem. 48 (2010) 542550.
[12] F.X. Hu, K.G. Noeh, L. Cen, E.T. Kang, Cellular response to magnetic nanopar-
ticles PEGylated via surface-initiated atom transfer radical polymerization,
Biomacromolecules 7 (2006) 809816.
[13] Q.L. Fan, K.G. Noeh, E.T. Kang, B. Shuter, S.C. Wang, Solvent-free atom trans-
fer radical polymerization for the preparation of poly(poly(ethyleneglycol)
monomethacrylate)-grafted Fe3 O4 nanoparticles: synthesis, characterization
and cellular uptake, Biomaterials 28 (2007) 54265436.
[14] Y Zhou, S.X. Wang, B.J. Ding, Z.M. Yang, Modication of magnetite nanoparticles
via surface-initiated atom transfer radical polymerization (ATRP), Chem. Eng.
J. 138 (2008) 578585.
[15] J.L. Zhang, R.S. Srivastava, R.D.K. Misra, Coreshell magnetite nanoparticles
surface encapsulated with smart stimuli-responsive polymer: synthesis, char-
acterization, and LCST of viable drug-targeting delivery, Langmuir 23 (2007)
63426351.
[16] R.A Frimpong, J.Z. Hilt, Poly(N-isopropyl acrylamide)-based hydrogel coatings
on magnetite nanoparticles via atom transfer radical polymerization, Nan-
otechnology 19 (2008) 175101.
[17] B. Mu, P. Liu, Y. Dong, C.Y. Lu, X.L. Wu, Superparamagnetic pH-sensitive multi-
layer hybrid hollow microspheres for targeted controlled release, J. Polym. Sci.
Part A: Polym. Chem. 48 (2010) 31353144.
[18] Y. Jin, L.N. Zhang, M. Zhang, L. Chen, P.C.K. Cheung, V.E.C. Oi, Y. Lin, Antitumor
activities of heteropolysaccharides of Poria cocos mycelia from different strains
and culture media, Carbohydr. Res. 338 (2003) 15171521.
[19] P. Liu, Facile preparation of polystyrene grafted calcium carbonate nanopar-
ticles via surface-initiated atom transfer radical polymerization, J. Disp. Sci.
Technol. 29 (2008) 10771080.
[20] M. Sangermano, A. Priola, G. Kortaberria, A. Jimeno, I. Garcia, I. Mondragon, G.
Rizza, Photopolymerization of epoxy coatings containing iron-oxide nanopar-
ticles, Macromol. Mater. Eng. 292 (2007) 956961.
[21] J. Pyun, S. Jia, T. Kowalewski, G.D. Patterson, K. Matyjaszewski, Synthesis and
characterization of organic/inorganic hybrid nanoparticles: kinetics of surface-
initiated atom transfer radical polymerization and morphology of hybrid
nanoparticle ultrathin lms, Macromolecules 36 (2003) 50945104.
[22] W. Wu, Q.G. He, H. Chen, J.X. Tang, L.B. Nie, Sonochemical synthesis, structure
and magnetic properties of air-stable Fe3 O4 /Au nanoparticles, Nanotechnology
18 (2007) 145609.
[23] H.G Schild, Preparation of novel acrylamide-based thermoresponsive polymer
analogues and their application as thermoresponsive chromatographic matri-
ces, Prog. Polym. Sci. 17 (1992) 163249.