Download as pdf or txt
Download as pdf or txt
You are on page 1of 32

Accepted Manuscript

Monodisperse and mesoporous walnut kernel-like SiO2/γ-Fe2O3 nanocomposite:


Synthesis, magnetic properties, and application in drug delivery

Wan Wei, Yu Ding, Ankang Zhao, Kun Ge, Cuimiao Zhang, Yanshen Li, Jinyu Zhang,
Guang Jia
PII: S0925-8388(17)33103-1
DOI: 10.1016/j.jallcom.2017.09.065
Reference: JALCOM 43121

To appear in: Journal of Alloys and Compounds

Received Date: 28 April 2017


Revised Date: 23 August 2017
Accepted Date: 6 September 2017

Please cite this article as: W. Wei, Y. Ding, A. Zhao, K. Ge, C. Zhang, Y. Li, J. Zhang, G. Jia,
Monodisperse and mesoporous walnut kernel-like SiO2/γ-Fe2O3 nanocomposite: Synthesis, magnetic
properties, and application in drug delivery, Journal of Alloys and Compounds (2017), doi: 10.1016/
j.jallcom.2017.09.065.

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT

Graphical Abstract

PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT

Monodisperse and mesoporous walnut kernel-like SiO2/γ-Fe2O3


nanocomposite: synthesis, magnetic properties, and application in
drug delivery
a *a
Wan Wei,a Yu Ding,b Ankang Zhao,a Kun Ge, Cuimiao Zhang, Yanshen Li,a
*a
Jinyu Zhang, a Guang Jia

PT
a
Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of
Education, Key Laboratory of Chemical Biology of Hebei Province, College of

RI
Chemistry and Environmental Science, Hebei University, Baoding 071002, P. R.
China

SC
b
China Lucky Group Corporation, Baoding 071054, P. R. China

U
AN
M

* Corresponding authors. Tel.: +86 312 5079359. Fax: +86 312 5079359

E-mail addresses: cmzhanghbu@163.com (C. Zhang); guangjia2001@163.com (G. Jia)


D
TE
C EP
AC

1
ACCEPTED MANUSCRIPT

Abstract

Mesoporous and magnetic nanomaterials have attracted great attention owing to

their unique characteristics and promising applications in drug delivery. In this

context, a novel method has been developed to engineer a nanostructure of unique

PT
walnut kernel-like SiO2/γ-Fe2O3 nanocomposite by incorporating magnetic γ-Fe2O3

RI
crystallites into mesoporous SiO2 nanospheres to exert their synergistic properties.

The as-obtained SiO2/γ-Fe2O3 nanospheres may be applied as a promising drug carrier

SC
due to suitable their advantages such as suitable particle size, mesoporous structure,

U
large specific surface area, high biocompatibility, good loading capacity, and long
AN
efficiency time of the drug release behavior. In particular, the composite exhibits

intense magnetic property, which may lead to the development of nanocomposite with
M

great potential for applications in drug targeting and magnetic hyperthermia therapy.
D
TE
EP

Keywords: SiO2/γ-Fe2O3; Nanospheres; Synthesis; Magnetic properties; Drug carrier


C
AC

2
ACCEPTED MANUSCRIPT

1. Introduction

The development of nanotechnology has strongly affected the synthesis and

application of nanoparticles and the use of nanotechnology in drug delivery is a

rapidly expanding field [1]. Recent research has focused on developing

PT
stimuli-responsive drug storage/release systems, which exhibit numerous advantages

RI
over the conventional forms of dosage, such as enhanced bioavailability, structurally

stable, greater efficacy and safety, targeted controllable release, and predictable

SC
therapeutic response [2-6]. Among these stimuli-responsive drug carriers, magnetic

U
iron oxide nanoparticles are of great interest for researchers from a broad range of
AN
disciplines due to their interesting inherent properties, such as superparamagnetism,

high specific surface area, avoiding insufficient or excessive drug dosing, minimizing
M

invasive damages to normal tissues, and fast response under applied external magnetic
D

field [7].
TE

Among various iron oxides, great attention has been paid on maghemite (γ-Fe2O3)

due to its excellent magnetic property and thermodynamic stability [8-11]. In


EP

particular, magnetic maghemite nanoparticles are a class of materials that are highly
C

suitable for applications in biomedical field due to their biocompatibility and


AC

superparamagnetic properties [12,13]. For example, the superparamagnetic

nanoparticles can be applied as a source of hyperthermia to cause the death of cancer

cells, and they can also provide magnetic guidance of the drug carrier to a specific

target. Moreover, combining maghemite with other functional materials would yield

composite particles with enhanced physical and chemical properties, and hence a

3
ACCEPTED MANUSCRIPT

wider range of applications can be expected. Huang et al. reported the rational design

and synthesis of γ-Fe2O3@Au magnetic gold nanoflowers and their applications for

cancer theranostics [14]. Caetano et al. described the sol–gel synthesis of

ureasil-PEO-γ-Fe2O3 nanocomposites by the conjugation of a semi-crystalline

PT
ureasil-poly(ethylene oxide) matrix loaded with a model drug and γ-Fe2O3

RI
nanoparticles for remotely triggered therapy [15]. Wu and co-workers reported the

fabrication of the magnetic metal-organic frameworks γ-Fe2O3@MOFs by an in situ

SC
pyrolysis method and investigated their applications in drug delivery field [16].

U
However, the application of γ-Fe2O3 nanoparticles is still greatly limited due to
AN
the particle aggregation, poor water-dispersion, and instability in acidic solutions.

Moreover, high performance in the function of specific biological applications


M

requires that the composites possess some unique features, such as spherical
D

morphology, narrow size distributions, large surface areas, and good dispersion in
TE

liquid media [17]. Therefore, the embedding of γ-Fe2O3 nanoparticles is imperative to

enhance γ-Fe2O3 nanoparticles absorbance, dispersion, and stability [18]. Among all
EP

these platforms, mesoporous silica (SiO2) nanospheres are considered as an ideal host
C

material for fabricating the magnetic mesoporous silica nanospheres due to their
AC

unique chemical and mechanical stability, high surface area, large pore volume with

tunable pore sizes, nontoxicity, biocompatibility, facility for surface modification, and

hydrophilicity [19,20]. The SiO2/γ-Fe2O3 composite nanoparticles exhibit the

desirable properties of magnetic nanoparticles while benefiting from the mesoporous

SiO2 [21,22]. Based on this principle, the magnetic nanocomposites prepared by

4
ACCEPTED MANUSCRIPT

encapsulating γ-Fe2O3 into ordered mesoporous silica is a promising material in

biomedical applications. However, these reported synthetic procedures are either

multistep or rather complex and also shared some other flaws and deficiencies such as

impurity of production, poor dispersity, and non-uniform particle size, and so on.

PT
Therefore, it remains a great challenge to develop a general and effective synthetic

RI
method for preparing monodisperse magnetic mesoporous SiO2/γ-Fe2O3 composite

nanoparticles with suitable size, uniform shape, and well-defined structure.

SC
In this paper, we reported a facile and efficient synthesis approach for the

U
fabrication of monodisperse, magnetic, and mesoporous γ-Fe2O3-incorporating
AN
mesoporous silica nanoparticles (SiO2/γ-Fe2O3) with uniform particle size by using

mesoporous silica nanospheres as template. Most importantly, the as-obtained


M

SiO2/γ-Fe2O3 mesoporous nanospheres can be used as an efficient drug carrier. A


D

typical antibiotic drug vancomycin, which is effective for inhibition the growth of
TE

gram-positive bacteria [23], was used as a model drug to evaluate the drug loading

and release behaviors. The as-synthesized SiO2/γ-Fe2O3 mesoporous nanospheres


EP

exhibit a high drug loading capacity and favorable release pattern, which may be
C

promising for applications in field of biomedical drug delivery.


AC

2. Experimental section

2.1. Preparation of mesoporous silica nanoparticles

The monodisperse mesoporous silica nanospheres were synthesized according to

the previously reported method with some modifications [24]. In a typical procedure,

0.4807 g of cetyl-trimethylammonium tosylate (CTATos) and 0.064 mL of

5
ACCEPTED MANUSCRIPT

triethanolamine (TEAH3) were dissolved into 25 mL of deionized water under

vigorous magnetic stirring at 80 oC for 1 h to obtain transparent solution. Then, 4.0

mL of tetraethyl orthosilicate (TEOS) was quickly added into the above solution and

the mixture was stirred at 80 oC for another 2 h. The obtained precipitate was

PT
collected by centrifugation, washing, and drying process.

RI
2.2. Synthesis of uniform SiO2/γ-Fe2O3 nanocomposite

In a typical synthesis, 0.0994 g of FeCl2·4H2O was dissolved in 20 mL of

SC
ethanol to obtain a transparent solution. Then 0.12 g of the as-obtained silica

U
nanospheres were dispersed into the above solution under vigorous stirring. The
AN
mixture was continuously stirred to evaporate ethanol at the room temperature until a

completely dried powder was obtained. Subsequently, this powder sample was placed
M

in graphite crucibles and then annealed at 500 oC for 2 h with a heating rate of 1
D

o
C/min to obtain the final product (denoted as SiO2/γ-Fe2O3).
TE

2.3. Preparation of drug storage/release system

Vancomycin (Van) was selected as the model drug to evaluate the drug storage
EP

and release behaviors of SiO2/γ-Fe2O3. Typically, 0.1 g of SiO2/γ-Fe2O3 was dispersed


C

in 10 mL of aqueous solution with an Van concentration of 20 mg/mL, and treated


AC

with ultrasound for 1 h. Then, the mixture was stirred at 37 oC for 48 h to reach the

equilibrium state and the Van-loaded samples were collected via centrifugation,

marked as Van-SiO2/γ-Fe2O3. To quantify the drug loading amount, the supernatant

was collected and the residual Van content was obtained by UV-vis spectrophotometer

measurement at the wavelength of 280 nm. Before determination, a calibration curve

6
ACCEPTED MANUSCRIPT

was recorded by measuring the absorbance of a series of Van solutions at different

concentrations. The drug loading capacity (DLC) was determined by the following

equation:
ML
DLC(%) = ×100%
MS

PT
Where DLC is the drug loading capacity, ML is the mass of the drug (mg) loaded in

RI
SiO2/γ-Fe2O3, MS is the mass of the drug delivery system.

To examine the release profile of Van from the nanocarrier, the powder (50 mg)

SC
of Van-SiO2/γ-Fe2O3 was dispersed in 2 mL of the release media, i.e., simulated body

U
fluid (SBF) and the mixture was sealed in a pretreated semipermeable dialysis bag,
AN
which was immersed into 23 mL of SBF with gentle shaking at 37 oC. The ionic

composition of the as-prepared SBF solution was similar to that of human body
M

plasma with a molar composition of 142.0/5.0/2.5/1.5/147.8/4.2/1.0/0.5 for


D

Na+/K+/Ca2+/Mg2+/Cl-/HCO-/HPO42-/SO42-, and the pH value of SBF is 7.40 [25].


TE

Sample solution (3 mL) at different predetermined time intervals were withdrawn and

immediately replenished with an equal volume of fresh SBF to keep the volume
EP

unchanged. The sample solution was then properly diluted and used to monitor the
C

amount of released Van by measuring the absorption band at 280 nm with UV-Vis
AC

spectrophotometer.

2.4. In vitro cytotoxicity of SiO2/γ-Fe2O3


The in vitro cytotoxicity was evaluated by performing a 3-[4,

5-dimethylthialzol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay of the Rat

liver (BRL-3A) cells [26,27]. In brief, BRL-3A cells were seeded in a 96-well

cell-culture plate with a density of 3×104 cells per well and then incubated at 37 oC

7
ACCEPTED MANUSCRIPT
for 12 h under 5% CO2. Thereafter, the sterilized SiO2/γ-Fe2O3 was added to the wells

at concentrations ranging from 3.125 to 100 µg/mL and co-cultured with the cells for

24 h. Then 10 µL of stock MTT (5 mg/mL) was added to each well and the cells were

incubated for another 4 h at 37 oC. Then, the medium containing MTT was removed

and 100 µL of dimethyl sulfoxide (DMSO) was added to each well to lyse the purple

PT
formazan crystals. The absorbance was monitored with a microplate reader

RI
(Molecular Devices Versamax, USA) at a wavelength of 570 nm. All measurements

were done in triplicate, and at least three independent experiments were carried out.

SC
For comparison, the in vitro cells viabilities and cumulative vancomycin release

profile of the pure SiO2 system without the magnetic component was performed by a

similar process.
U
AN
2.5. Characterizations
M

The crystalline phase of the nanomaterials was determined by powder X-ray

diffraction (XRD) performed on a D8 Advance diffractometer (Bruker). The


D

micrographic characterization and energy dispersive X-ray spectrometry (EDX) of the


TE

SiO2/γ-Fe2O3 was inspected using a scanning electron microscope (SEM; JSM-7500F,


EP

JEOL) and transmission electron microscopy (TEM; FEI Tecnai G2 S-Twin). The

magnetic properties of samples were investigated using a physical property


C

measurement system [PPMS-9T (EC-II), Quantum Design, USA]. Fourier transform


AC

infrared spectroscopy (FT-IR) spectra were recorded on a Perkin-Elmer 580B IR

spectrophotometer. Nitrogen adsorption/desorption isotherm was obtained using a

Micromeritics ASAP 2020M apparatus. The specific surface area was determined by

the Brunauer-Emmett-Teller (BET) method using the data between 0.05 and 0.35 just

before the capillary condensation. X-ray photoelectron spectra (XPS) were taken on a

8
ACCEPTED MANUSCRIPT

VG ESCALAB MK II electron energy spectrometer. The drug loading and release

rate were detected by UV-Vis spectrophotometry (UV-Vis, TU-1950). All

measurements were performed at room temperature.

3. Results and discussion

PT
3.1. Phase, structure, and morphology.

RI
The phase structure and composition of the SiO2 and SiO2/γ-Fe2O3 samples were

determined by XRD (Fig. 1). In Fig. 1a, one can observe a broad signal located at

SC
about 2θ = 23°, which is the typical characteristic pattern of amorphous silica. In Fig.

U
1b, several new sharp diffraction peaks at 2θ = 30°, 35.4°, 43°, 53.4°, 57° and 62.5°
AN
appear besides the broad peak, which are well indexed to the cubic inverse spinel

structure of Fe2O3 (magnetite, γ-Fe2O3) [JCPDS No. 39-1346; Space group P4132
M

(213)]. The XRD diffraction patterns of maghemite and magnetite (Fe3O4) are so
D

similar, so it is difficult to distinguish the two phases just by XRD analysis. From the
TE

inset in Fig.7, it can be seen that the color of the nanocomposite is reddish brown,

indicating that the component of the magnetic nanoparticles are γ-Fe2O3 [21,28]. To
EP

further verify the crystal phase, we directly synthesized the magnetic sample without
C

adding silica nanospheres during the synthesis process and performed their EDX
AC

spectrum (Fig. S1, supplementary information). The molar ratio of Fe/O for the

as-obtained magnetic sample is calculated to be 0.64, which is in good accordance

with γ-Fe2O3. On the basis of the result mentioned above, it can be concluded that the

as-synthesized magnetic nanoparticles are composed of maghemite (γ-Fe2O3).

Moreover, no impurity peaks can be detected, indicating that the pure cubic phase of

9
ACCEPTED MANUSCRIPT

γ-Fe2O3 is obtained by this synthesis route. The result also reveals that the crystalline

γ-Fe2O3 has been successfully incorporated into mesoporous SiO2 nanospheres.

Although the preparation of SiO2 with different morphologies were extensively

investigated, the fabrication of monodisperse SiO2 nanospheres with smaller particle

PT
size (< 200 nm), which are favorable for the applications in biomedical fields, still

RI
remains a challenge [24,29]. The morphology and particle size of the samples were

examined by SEM. Fig. 2 shows the SEM images of the SiO2 and SiO2/γ-Fe2O3

SC
samples. The low-magnification SEM image (Fig. 2a) reveals that the mesoporous

U
SiO2 consists of relatively uniform and well-dispersed nanospheres with diameters of
AN
about 120 nm, which are non-aggregated with narrow size distribution. These

nanospheres exhibit a unique walnut kernel-like structure. The enlarged SEM image
M

(Fig. 2b) clearly indicates that the spheres possess corrugated channel morphologies
D

and large surface areas. Fig. 2c,d show the SEM images of the SiO2/γ-Fe2O3
TE

composite. After incorporating γ-Fe2O3 nanocrystallites into SiO2 nanospheres, it can

be seen that the particle size, monodispersity, dispersion, and morphology of the
EP

as-obtained SiO2/γ-Fe2O3 are mainly maintained (Fig. 2c,d), indicating that the
C

introduction of γ-Fe2O3 have little effect on the shape and size of nanospheres, except
AC

for the external channels of SiO2/γ-Fe2O3 becomes slightly deeper and wider in

comparison with that of bare SiO2. The result may be due to removal of cationic

surfactants or other organic components resided within the mesopore channels of

SiO2/γ-Fe2O3 during the annealing process.

As depicted in Fig. 3, the morphology and microstructure of the as-synthesized

10
ACCEPTED MANUSCRIPT

SiO2/γ-Fe2O3 sample were further evidenced by TEM. We can see from Fig. 3 that the

well-dispersed SiO2/γ-Fe2O3 nanospheres with diameters at about 120 nm are obtained,

corresponding well with the SEM images. It can be also seen that the sample exhibits

full pore connectivity and more tortuous walls, which may which may induce larger

PT
surface area and pore volume. Moreover, the obvious lattice fringes in the HRTEM

RI
image (Fig. 3c) confirm the high crystallinity of the γ-Fe2O3 nanocrystallites. The

EDX spectrum of the SiO2/γ-Fe2O3 sample confirms the presence of silicon (Si),

SC
oxygen (O), and iron (Fe) elements (Fig. 3d). No other impurity peaks can be detected,

U
which can effectively support the XRD result of the sample.
AN
Fig. 4 shows the survey XPS narrow scan spectra of the SiO2/γ-Fe2O3

nanocomposite. The main peaks at about 103.9, 533.1, and 711.5 eV can be readily
M

attributed to the binding energy of Si2p, O1s, and Fe2p, which originate from the
D

SiO2/γ-Fe2O3 composite. By combination of the previous XRD and EDX results, it


TE

can be deduced that the γ-Fe2O3 nanocrystallites have been successfully incorporated

into the SiO2 framework. The minor peak of C1s located at 284.8 can be also detected,
EP

which can be attributed to the residual alkyl group of surfactant molecules.


C

3.2. Mesoporous and in vitro cytotoxicity


AC

The textural properties of the SiO2/γ-Fe2O3 nanocomposite were investigated by

nitrogen physical adsorption/desorption measurements. The N2 adsorption/desorption

isotherm of SiO2/γ-Fe2O3 nanospheres (Fig. 5) exhibits representative IV-typed

adsorption/desorption isotherms with typical H1-hysteresis loops according to the

IUPAC classification, which indicates the presence of the mesoporous structure. The

11
ACCEPTED MANUSCRIPT

BET surface area and pore volume of SiO2/γ-Fe2O3 are calculated to be about 185.36

m2/g and 0.67 cm3/g. The high surface area and pore volume of the sample are

beneficial for loading large amount of drug molecules.

A good biocompatibility and efficient localization of nanomaterials is an

PT
essential prerequisite and crucial factor for the actual application as a potential drug

RI
carrier in biomedical fields. In order to evaluate the potential biocompatibility of the

nanocomposites, the MTT cell viability assays were performed on the rat liver cells

SC
(BRL-3A). As show in Fig. 6, the SiO2/γ-Fe2O3 composite shows no appreciable

U
cytotoxicity against the BRL-3A cells after incubation for 24 h with SiO2/γ-Fe2O3 at
AN
different concentrations ranged from 3.125 to 50 µg/mL. Moreover, the cell viability

is more than 100% even incubation for 24 h at high concentrations of the sample. The
M

MTT assay results indicate that the hybrid SiO2/γ-Fe2O3 nanospheres are
D

biocompatible and can be potentially applied as a promising drug carrier in


TE

biomedical field.

3.3. Magnetic and drug loading and release properties


EP

Preserving the magnetic property is an important parameter for surface


C

engineering of magnetic nanoparticles. The magnetic hysteresis loops of the


AC

synthesized SiO2/γ-Fe2O3 and Van-SiO2/γ-Fe2O3 are shown in Fig. 7. The

field-dependent magnetization plots illustrate that the saturation magnetization value

of the magnetic SiO2/γ-Fe2O3 drug carrier is 16.61 emu/g. After loading Van

molecules, the saturation magnetization value of the as-obtained Van-SiO2/γ-Fe2O3

drug delivery system decreases to 13.94 emu/g. The diamagnetic contribution of the

12
ACCEPTED MANUSCRIPT

Van molecules results in a low mass fraction of the γ-Fe2O3 magnetic substance,

which provides evidence that the Van molecules have been successfully loaded into

SiO2/γ-Fe2O3 composite. When the SiO2/γ-Fe2O3 nanospheres are dispersed in H2O,

they can be separated through exposure to an external magnetic force. The result

PT
indicates that the SiO2/γ-Fe2O3 nanocomposite can exhibit excellent magnetic

RI
responsivity and redispersibility in aqueous solution and may find potential

applications for targeting and magnetic drug delivery.

SC
The FT-IR spectra were performed to validate the composition of the

U
SiO2/γ-Fe2O3 and the encapsulation of vancomycin in SiO2/γ-Fe2O3. Fig. 8 presents
AN
the FT-IR spectra of SiO2/γ-Fe2O3, Van-SiO2/γ-Fe2O3, and free vancomycin,

respectively. For the SiO2/γ-Fe2O3 sample (Fig. 8a), the absorption bands at 3450 and
M

1633 cm-1 are assigned to the stretching vibration of −OH bond and the bending
D

vibration of H2O. The result reveals that the −OH groups and H2O are present in
TE

SiO2/γ-Fe2O3 sample, which is important for bonding hydrophilic vancomycin

molecules. In addition, the characteristic vibrations of silica associated with Si−OH


EP

(960 cm-1), Si−O−Si (1096 cm-1 and 805 cm-1), and Si−O (465 cm-1) are also observed,
C

confirming the existence of SiO2. The appearance of the band at 570 cm-1 is ascribed
AC

to the typical Fe−O stretching vibration of the γ-Fe2O3, indicating that the γ-Fe2O3

nanocrystallites are successfully anchored into SiO2 [30]. As for Van-SiO2/γ-Fe2O3

(Fig. 8b), the appearance of the absorption bands at 1653, 1508 and 1408 cm-1

confirms the presence of vancomycin in SiO2/γ-Fe2O3. The band at 1653 cm-1 may be

assigned to the C=C aromatic stretching or C=O stretching vibrational groups. The

13
ACCEPTED MANUSCRIPT

minor peaks located at 1508 and 1408 cm-1 are attributed to aromatic adsorption.

Furthermore, the weak absorption bands assigned to the C-Hx stretching vibrations at

about 2921 and 2970 cm-1 further confirm the successful loading of vancomycin

molecules into SiO2/γ-Fe2O3 surface. The result mentioned above can be well

PT
validated by the FT-IR spectrum of the free vancomycin (Fig. 8c).

RI
In this study, vancomycin, an antibiotic, was used as a model drug to investigate

the drug loading and controlled release behaviors of mesoporous SiO2/γ-Fe2O3

SC
composite. The drug loading capacity is determined to be 169.3 mg drug/g carrier.

U
According to the two equations above, we plotted the release curve for Van in the SBF
AN
media, as shown in Fig. 9. The Van calibration curve agrees well with the Lambert

and Beers law and the corresponding equation is as follows [31]:


M

A= 0.0421×C-4.09091×10-4 (inset in Fig. 9),


D

where A is the absorbance and C is the concentration of Van in SBF (µg/ml). The
TE

corrected concentration of released Van was determined on the equation below:

V t −1
Ccort = Capp + ∑ Capp
EP

Vt 0

where Ccort is the corrected concentration of released Van at time t, Capp is the
C
AC

apparent concentration of released Van of the tested samples, V is the volume of the

tested sample, and Vt is the total volume of solvent SBF.

It can be seen from Fig. 9 that the Van-SiO2/γ-Fe2O3 drug delivery system

exhibits a drug-pronounced initial burst release within 13 h, followed by the slow

sustained release of Van molecules. The release time of the systems can last for more

than 50 h. The initial burst release may be due to the Van weakly and physical

14
ACCEPTED MANUSCRIPT

adsorption on the exterior surface of SiO2/γ-Fe2O3, which induces the Van molecules

easily diffusing into the medium and prompts the fast release of drug molecules. The

following slow release may be attributed to the strong interaction (hydrogen bonding)

between Van molecules that adsorbed in the mesopores and the drug carrier. For

PT
comparison, the in vitro BRL-3A cells viabilities and cumulative vancomycin release

RI
profile of the pure SiO2 system without the magnetic component was performed (Fig.

S2, supplementary information). The results indicate that the pure SiO2 system also

SC
exhibits good biocompatibility and sustained drug release profile, which are similar to

U
that of the SiO2/γ-Fe2O3 sample. Considering the combined advantages of uniform
AN
particle size, mesoporous structure, good biocompatibility, sustained drug release, and

magnetic behavior, the as-synthesized SiO2/γ-Fe2O3 nanocomposite may find the


M

potential application in targeted drug delivery.


D
TE

4. Conclusions

In summary, the magnetic and mesoporous SiO2/γ-Fe2O3 nanocomposite has


EP

been fabricated by a simple and effective approach. The sample was characterized by
C

XRD, SEM, TEM, EDX, XPS, FT-IR, N2 adsorption/desorption isotherms, and MTT
AC

assays. SEM and TEM images show that the composite inherits the uniform spherical

morphology and good dispersion of the SiO2 nanospheres. FT-IR spectra reveal that

the vancomycin drug molecules have been successfully loaded into the mesoporous

SiO2 framework. The Van-SiO2/γ-Fe2O3 system shows a drug-pronounced initial burst

release followed by a slow sustained release process. Moreover, the nanocomposite

exhibits intense magnetic property and good biocompatibility. Due to the proper

15
ACCEPTED MANUSCRIPT

particle size, mesoporous structure, good biocompatibility, and magnetic properties,

sustained drug release pattern, the as-synthesized SiO2/γ-Fe2O3 nanocomposite may

function as a promising targeting drug carrier in biomedical field. Furthermore, this

synthetic strategy may pave a critical way for the design and synthesis of

PT
incorporating functional nanoparticles into mesoporous structures to exert their

synergistic properties.

RI
SC
Acknowledgements

This research was supported by the National Natural Science Foundations of

U
China (21301046, 51302062), Natural Science Foundations of Hebei Province
AN
(B2017201125, B2017201100, B2016201209), the Second Batch of Top Youth Talent
M

Support Program of Hebei Province, Distinguished Young Scholars Fund of Hebei

University (2015JQ04), Key Program of Hebei University Scientific Research Project


D

(ZD2015031), and China Postdoctoral Science Foundation (2013M530119,


TE

2014T70226).
C EP
AC

16
ACCEPTED MANUSCRIPT

References

[1] H. Amir, A. P. Homayon, F. Mehdi, F. Fatemeh, Mater. Sci. Eng. C. Mater. Biol.

Appl. 67 (2016) 42-50.

[2] W. Xiong, R. Mazid, L. W. Yap, X. Y. Li, W. L. Cheng, Nanoscale 6 (2014)

PT
14388-14393.

RI
[3] X. Zhang, P. P. Yang, Y. L. Dai, P. A. Ma, X. J. Li, Z. Y. Cheng, J. Lin, Adv. Funct.

Mater. 23 (2013) 4067-4078.

SC
[4] N. S. Manam, W. S. W. Harun, D. N. A. Shri, S. A. C. Ghani, T. Kurniawan, M. H.

U
Ismail, M. H. I. Ibrahim, J. Alloys Comp. 701 (2017) 698-715.
AN
[5] Y. C. Wang, M. S. Shim, N. S. Levinson, H. W. Sung, Y. N. Xia, Adv. Funct.

Mater. 14 (2014) 4206-4220.


M

[6] P. Chen, B. Cui, X. Cui, W. Zhao, Y. Bu, Y. Wang, J. Alloys Comp. 699 (2017)
D

526-533.
TE

[7] H. Y. Xu, Z. P. Aguilar, L. Yang, M. Kuang, H. W. Duan, Y. H. Xiong, H. Wei, A.

Wang, Biomaterials 32 (2011) 9758-9765.


EP

[8] B. Liao, Z. An, J. Zhang, RSC Adv. 6 (2016) 47089-47095.


C

[9] D. Maiti, S. Mukhopadhyay, S. C. Mohanta, A. Saha, P. S. Devi, J. Alloys Comp.


AC

653 (2015) 187-194.

[10] L. Kong, X. W. Yin, Y. J. Zhang, X. Y. Yuan, Q. Li, F. J. Ye, J. Phys. Chem. C

117 (2013) 19701-19711.

[11] H. Zhang, X. Liang, C. Yang, C. Niu, J. Wang, X. Su, J. Alloys Comp. 688 (2016)

1019-1027.

17
ACCEPTED MANUSCRIPT

[12] L. Mohammed, H. G. Gomaa, D. Ragab, Jesse Zhu, Particuology 30 (2017) 1-14.

[13] C. S. Lewis, L. Torres, J. T. Miyauchi, C. Rastegar, J. M. Patete, J. M. Smith, S.

S. Wong, S. E. Tsirka, Toxicol. Res. 5 (2016) 836-847.

[14] J. Huang, M. Guo, H. Ke, C. Zong, B. Ren, G. Liu, H. Shen, Y. Ma, X. Wang, H.

PT
Zhang, Z. Deng, H. Chen, Z. Zhang, Adv. Mater. 27 (2015) 5049-5056.

RI
[15] B. L. Caetano, C. Guibert, R. Fini, J. Fresnais, S. H. Pulcinelli, C. Ménager, C. V.

Santilli, RSC Adv. 6 (2016) 63291-63295.

SC
[16] Y. N. Wu, M. Zhou, S. Li , Z. Li , J. Li , B. Wu , G. Li, F. Li, X. Guan, Small 10

U
(2014) 2927-2936.
AN
[17] S. J. Guo, D. Li, L. X. Zhang, J. Li, E. K. Wang. Biomaterials 30 (2009)

1881-1889.
M

[18] W. Zhang, X. Shi, Y. Zhang, W. Gu, B. Li, Y. Xian, J. Mater. Chem. A1 (2013),
D

1745-1753.
TE

[19] Y. Wang, W. Shi, S. S.Wang, C. Y. Li, M. Qian, J. Chen, R. Q. Huang, Carbon

108 (2016) 146-153.


EP

[20] B. Zhang, S. Yang, Y. Zhang, Q. X. Wang, T. R. Ren, Colloids Surf. B


C

Biointerfaces 131 (2015) 129-135.


AC

[21] A. Teleki, F. L. Haufe, A. M. Hirt, S. E. Pratsinisa, G. A. Sotiriou, RSC Adv. 6

(2016) 21503-21510.

[22] E. Taboada, R. Solanas, E. Rodríguez, R. Weissleder, A. Roig, Adv. Funct. Mater.

19 (2009) 2319-2324.

[23] G. B. Qi, L. L. Li, F. Q. Yu, H. Wang, ACS Appl. Mater. Interfaces 5 (2013)

18
ACCEPTED MANUSCRIPT

10874-10881.

[24] K. Zhang, L. Xu, J. Jiang, N. Calin, K. F. Lam, S. J. Zhang, H. Wu, G. Wu, B.

Albela, L. Bonneviot, P. Wu, J. Am. Chem. Soc. 135 (2013) 2427-2430.

[25] M. Bohnera, J. Lemaitre, Biomaterials 30 (2009) 2175-2179 .

PT
[26] Mosmann, T. J. Immunol. Methods 65 (1983) 55-63.

RI
[27] K. Ge, C. Zhang, W. Sun, H. Liu, Y. Jin, Z. Li, X. J. Liang, G. Jia, J. Zhang, ACS

Appl. Mater. Interfaces 8 (2016) 25078-25086.

SC
[28] M. Hu, A. A. Belik, M. Imura, K. Mibu, Y. Tsujimoto, Y. Yamauchi, Chem. Mater.

U
24 (2012) 2698-2707.
AN
[29] K. Ge, C. Zhang, G. Jia, H. Ren, J. Wang, A. Tan, X. J. Liang, A. Zang, J. Zhang,

ACS Appl. Mater. Interfaces 7 (2015) 10905-10914.


M

[30] H. Wang, Y. N. Chen, Y. M. Wei, RSC Adv. 6 (2016) 34770-34781.


D

[31] H. Hata, S. Saeki, T. Kimura, Y. Sugahara, K. Kuroda, Chem. Mater. 11 (1999)


TE

1110-1119.
C EP
AC

19
ACCEPTED MANUSCRIPT

Figure captions

Fig. 1 XRD patterns of (a) SiO2 and (b) SiO2/γ-Fe2O3 samples. The standard data of

cubic γ-Fe2O3 (JCPDS No. 39-1346) is presented as a reference.

Fig. 2 SEM images of (a,b) SiO2 and (c,d) SiO2/γ-Fe2O3 samples.

PT
Fig. 3 (a,b) TEM, (c) HRTEM images, and (d) EDX spectrum of SiO2/γ-Fe2O3

RI
sample.

Fig. 4 XPS spectra of (a) SiO2/γ-Fe2O3, and (b) O1s, (c) Fe2p, and (d) Si2p for

SC
SiO2/γ-Fe2O3.

U
Fig. 5 N2 adsorption/desorption isotherm of mesoporous SiO2/γ-Fe2O3 sample.
AN
Fig. 6 In vitro BRL-3A cells viabilities after incubation for 24 h with SiO2/γ-Fe2O3 at

different concentrations by MTT assay.


M

Fig. 7 Magnetic hysteresis loops of (a) SiO2/γ-Fe2O3 and (b) Van-SiO2/γ-Fe2O3


D

samples. The photograph inset shows the dispersion of SiO2/γ-Fe2O3 nanospheres


TE

before (left) and after (right) magnetic separation by an external magnetic field.

Fig. 8 FT-IR spectra of (a) SiO2/γ-Fe2O3, (b) Van-SiO2/γ-Fe2O3, and (c) free
EP

vancomycin.
C

Fig. 9 Cumulative vancomycin release profiles of Van-SiO2/γ-Fe2O3 in SBF as a


AC

function of release time. Inset is the corresponding calibration curve.

20
ACCEPTED MANUSCRIPT

PT
RI
U SC
AN
M
D

Figure 1
TE
EP
C
AC

21
ACCEPTED MANUSCRIPT

PT
RI
U SC
AN
M
D
TE

Figure 2
EP
C
AC

22
ACCEPTED MANUSCRIPT

PT
RI
U SC
AN
M
D
TE

Figure 3
EP
C
AC

23
ACCEPTED MANUSCRIPT

PT
RI
U SC
AN
M
D
TE

Figure 4
EP
C
AC

24
ACCEPTED MANUSCRIPT

PT
RI
U SC
AN
M
D
TE
EP

Figure 5
C
AC

25
ACCEPTED MANUSCRIPT

PT
RI
U SC
AN
M
D
TE

Figure 6
EP
C
AC

26
ACCEPTED MANUSCRIPT

PT
RI
U SC
AN
M
D
TE
EP

Figure 7
C
AC

27
ACCEPTED MANUSCRIPT

PT
RI
U SC
AN
M
D

Figure 8
TE
EP
C
AC

28
ACCEPTED MANUSCRIPT

PT
RI
U SC
AN
M
D
TE

Figure 9
EP
C
AC

29
ACCEPTED MANUSCRIPT

Highlights

● Mesoporous SiO2/γ-Fe2O3 nanocomposite was synthesized by a simple method.

● The sample consists of monodisperse nanospheres with narrow size distribution.

PT
● The sample exhibits intense magnetic property and sustained drug release patterns.

RI
● The nanocomposite may function as a promising targeting drug carrier.

U SC
AN
M
D
TE
C EP
AC

You might also like