CL-150104
Received: February 2, 2015 | Accepted: March 8, 2015 | Web Released: March 14, 2015
Doxorubicin-loaded Fe O @SiO Nanoparticles as Magnetic Targeting Agents
3
4
2
for Combined Photothermal-chemotherapy of Cancer
Bei Ding,1 Song Shen,*1,# Lin Wu, Xueyong Qi, Haihua Ni, and Yanru Ge*
,#
2
1
3
1
1
School of Pharmacy, Jiangsu University, Zhenjiang 212013, P. R. China
Affiliated Hospital of Jiangsu University, Zhenjiang 212013, P. R. China
2
3
Yangtze River Pharmaceutical Group, Haiji Pharmaceutical Company, Taizhou 225300, P. R. China
(
E-mail: geyanru@ujs.edu.cn, phar@ujs.edu.cn)
Specific photothermal-chemotherapy is a promising tool in
the treatment of the cancer. We developed silica-coated Fe O
A
B
3
4
nanoparticles as photothermal agents and magnetic targeting
drug delivery system. Doxorubicin-loaded silica-coated Fe3O4
nanoparticles showed pH-responsive release properties. A
synthetic antitumor effect of photothermal-chemotherapy was
realized on MCF-7 cells.
5
0 nm
50 nm
Over the past decade, cancer has become a serious disease
endangering human health. Cancer hyperthermia has been
actively developed into an appealing treatment method, in
which thermal therapy destroys tumor cells at mild temperatures
Figure 1. Transmission electron microscope (TEM) images. (A)
Fe O nanoparticles. (B) Fe O @SiO nanoparticles.
3
4
3
4
2
(
4045 °C). Photothermal therapy (PTT), a typical form of
A
B
cancer hyperthermia, is a recently developed technique to kill
tumor cells by mediating the conversion of near-infrared (NIR)
laser into heat.
1
,2
Many endeavors have been reported on
36
photothermal nanomaterials such as gold nanomaterials,
carbon nanotubes,7,8 and graphene.
9,10
These materials have
limited use in clinical therapy due to their high toxicity.
Therefore, it is essential to develop novel PTT agents with low
toxicity and favorable biocompatibility.
Recently, several studies have reported the photothermal
1
115
effect of the magnetic composites in vitro as well as in vivo.
Figure 2. The temperature images and curves of different concen-
trations of Fe3O4@SiO2 suspensions under NIR laser irradiation
(808 nm, 2 W cm ).
However, magnetic nanoparticles are not suitable for biological
applications due to hydrophobicity, aggregation, and poor water-
¹2
dispersion. Surface modification by materials such as silica is
an essential method to solve these problems.1
6,17
Silica-coated
exhibited optical absorption in the near IR (NIR) region (ca.
808 nm), which is the common wavelength used for photo-
thermal therapy (Figure S3 in Supporting Information).
Fe O nanoparticles possess favorable biochemical stability,
3
4
nontoxicity, and biocompatibility. Doxorubicin (DOX), a tradi-
tional anticancer drug, has limited use in clinical therapy owing
to its systemic toxicity and side effects.
In this work, we developed a magnetically guided drug
delivery system for photothermal-chemotherapy of tumor,
utilizing Fe O @SiO nanoparticles as photothermal agents.
DOX-loaded Fe3O4@SiO2 nanoparticles can be employed in
tumor targeting therapy. The antitumor effect of combined
photothermal-chemotherapy was studied on MCF-7 cells. The
combined treatment showed higher therapeutic effect and would
be a potential approach for treating patients.
The sizes and morphologies of all the nanoparticles were
analyzed using a transmission electron microscopy (TEM). The
Fe3O4 and Fe3O4@SiO2 nanoparticles had uniform spherical
structures with average diameter of «20 and «50 nm, respec-
tively (Figure 1). The corresponding size distribution histograms
are shown in Figure S1 (Figure S1 in Supporting Information).
The SiO2 layers coated onto the Fe3O4 nanoparticles were
confirmed by Fourier transform infrared (FTIR) spectroscopy
The photothermal temperature images induced by the NIR
laser were recorded by IR camera (Figure 2A). The temperature
of Fe3O4@SiO2 suspensions was irradiation time- and concen-
tration-dependent. The temperature was increased from 27 to
¹1
76 °C at the concentration of 500 ¯g mL within 8 min after
NIR irradiation. In comparison, the temperature of water was
increased by only 10 °C after NIR irradiation for 8 min
(Figure 2B). The results revealed that the Fe O @SiO nano-
3
4
2
3
4
2
particles would be ideal photothermal agents.
Drug loading capacity was enhanced significantly with
increase of pH. The loading capacity reached 36%, 41%, and
57%, respectively, at pH 5.0, 6.5, and 7.4. It might be that the
hydrophobicity of DOX was enhanced at high pH and the
hydrophobic interaction between DOX and the nanoparticles
was increased as well. The hydrophobic interaction between
DOX and nanoparticles were weakened under acidic conditions
and the loading capacity decreased gradually. In water, DOX
could be loaded into the nanoparticles with loading capacity of
about 35% (Figure 3A). We also found that DOX had better
(
Figure S2 in Supporting Information). The Fe3O4@SiO2
© 2015 The Chemical Society of Japan