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J Jallcom 2017 09 065
J Jallcom 2017 09 065
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
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.
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Graphical Abstract
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Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of
Education, Key Laboratory of Chemical Biology of Hebei Province, College of
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Chemistry and Environmental Science, Hebei University, Baoding 071002, P. R.
China
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China Lucky Group Corporation, Baoding 071054, P. R. China
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* Corresponding authors. Tel.: +86 312 5079359. Fax: +86 312 5079359
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Abstract
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walnut kernel-like SiO2/γ-Fe2O3 nanocomposite by incorporating magnetic γ-Fe2O3
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crystallites into mesoporous SiO2 nanospheres to exert their synergistic properties.
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due to suitable their advantages such as suitable particle size, mesoporous structure,
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large specific surface area, high biocompatibility, good loading capacity, and long
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efficiency time of the drug release behavior. In particular, the composite exhibits
intense magnetic property, which may lead to the development of nanocomposite with
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great potential for applications in drug targeting and magnetic hyperthermia therapy.
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1. Introduction
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stimuli-responsive drug storage/release systems, which exhibit numerous advantages
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over the conventional forms of dosage, such as enhanced bioavailability, structurally
stable, greater efficacy and safety, targeted controllable release, and predictable
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therapeutic response [2-6]. Among these stimuli-responsive drug carriers, magnetic
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iron oxide nanoparticles are of great interest for researchers from a broad range of
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disciplines due to their interesting inherent properties, such as superparamagnetism,
high specific surface area, avoiding insufficient or excessive drug dosing, minimizing
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invasive damages to normal tissues, and fast response under applied external magnetic
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field [7].
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Among various iron oxides, great attention has been paid on maghemite (γ-Fe2O3)
particular, magnetic maghemite nanoparticles are a class of materials that are highly
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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
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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
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ureasil-poly(ethylene oxide) matrix loaded with a model drug and γ-Fe2O3
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nanoparticles for remotely triggered therapy [15]. Wu and co-workers reported the
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pyrolysis method and investigated their applications in drug delivery field [16].
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However, the application of γ-Fe2O3 nanoparticles is still greatly limited due to
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the particle aggregation, poor water-dispersion, and instability in acidic solutions.
requires that the composites possess some unique features, such as spherical
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morphology, narrow size distributions, large surface areas, and good dispersion in
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enhance γ-Fe2O3 nanoparticles absorbance, dispersion, and stability [18]. Among all
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these platforms, mesoporous silica (SiO2) nanospheres are considered as an ideal host
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material for fabricating the magnetic mesoporous silica nanospheres due to their
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unique chemical and mechanical stability, high surface area, large pore volume with
tunable pore sizes, nontoxicity, biocompatibility, facility for surface modification, and
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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.
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Therefore, it remains a great challenge to develop a general and effective synthetic
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method for preparing monodisperse magnetic mesoporous SiO2/γ-Fe2O3 composite
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In this paper, we reported a facile and efficient synthesis approach for the
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fabrication of monodisperse, magnetic, and mesoporous γ-Fe2O3-incorporating
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mesoporous silica nanoparticles (SiO2/γ-Fe2O3) with uniform particle size by using
typical antibiotic drug vancomycin, which is effective for inhibition the growth of
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gram-positive bacteria [23], was used as a model drug to evaluate the drug loading
exhibit a high drug loading capacity and favorable release pattern, which may be
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2. Experimental section
the previously reported method with some modifications [24]. In a typical procedure,
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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
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collected by centrifugation, washing, and drying process.
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2.2. Synthesis of uniform SiO2/γ-Fe2O3 nanocomposite
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ethanol to obtain a transparent solution. Then 0.12 g of the as-obtained silica
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nanospheres were dispersed into the above solution under vigorous stirring. The
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mixture was continuously stirred to evaporate ethanol at the room temperature until a
completely dried powder was obtained. Subsequently, this powder sample was placed
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in graphite crucibles and then annealed at 500 oC for 2 h with a heating rate of 1
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C/min to obtain the final product (denoted as SiO2/γ-Fe2O3).
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Vancomycin (Van) was selected as the model drug to evaluate the drug storage
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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,
was collected and the residual Van content was obtained by UV-vis spectrophotometer
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concentrations. The drug loading capacity (DLC) was determined by the following
equation:
ML
DLC(%) = ×100%
MS
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Where DLC is the drug loading capacity, ML is the mass of the drug (mg) loaded in
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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)
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of Van-SiO2/γ-Fe2O3 was dispersed in 2 mL of the release media, i.e., simulated body
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fluid (SBF) and the mixture was sealed in a pretreated semipermeable dialysis bag,
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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
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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
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unchanged. The sample solution was then properly diluted and used to monitor the
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amount of released Van by measuring the absorption band at 280 nm with UV-Vis
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spectrophotometer.
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
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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
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formazan crystals. The absorbance was monitored with a microplate reader
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(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.
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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.
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2.5. Characterizations
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JEOL) and transmission electron microscopy (TEM; FEI Tecnai G2 S-Twin). The
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
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3.1. Phase, structure, and morphology.
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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
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about 2θ = 23°, which is the typical characteristic pattern of amorphous silica. In Fig.
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1b, several new sharp diffraction peaks at 2θ = 30°, 35.4°, 43°, 53.4°, 57° and 62.5°
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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
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(213)]. The XRD diffraction patterns of maghemite and magnetite (Fe3O4) are so
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similar, so it is difficult to distinguish the two phases just by XRD analysis. From the
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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
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further verify the crystal phase, we directly synthesized the magnetic sample without
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adding silica nanospheres during the synthesis process and performed their EDX
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spectrum (Fig. S1, supplementary information). The molar ratio of Fe/O for the
with γ-Fe2O3. On the basis of the result mentioned above, it can be concluded that the
Moreover, no impurity peaks can be detected, indicating that the pure cubic phase of
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γ-Fe2O3 is obtained by this synthesis route. The result also reveals that the crystalline
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size (< 200 nm), which are favorable for the applications in biomedical fields, still
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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
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samples. The low-magnification SEM image (Fig. 2a) reveals that the mesoporous
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SiO2 consists of relatively uniform and well-dispersed nanospheres with diameters of
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about 120 nm, which are non-aggregated with narrow size distribution. These
nanospheres exhibit a unique walnut kernel-like structure. The enlarged SEM image
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(Fig. 2b) clearly indicates that the spheres possess corrugated channel morphologies
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and large surface areas. Fig. 2c,d show the SEM images of the SiO2/γ-Fe2O3
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be seen that the particle size, monodispersity, dispersion, and morphology of the
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as-obtained SiO2/γ-Fe2O3 are mainly maintained (Fig. 2c,d), indicating that the
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introduction of γ-Fe2O3 have little effect on the shape and size of nanospheres, except
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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
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SiO2/γ-Fe2O3 sample were further evidenced by TEM. We can see from Fig. 3 that the
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
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surface area and pore volume. Moreover, the obvious lattice fringes in the HRTEM
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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),
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oxygen (O), and iron (Fe) elements (Fig. 3d). No other impurity peaks can be detected,
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which can effectively support the XRD result of the sample.
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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
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attributed to the binding energy of Si2p, O1s, and Fe2p, which originate from the
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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,
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IUPAC classification, which indicates the presence of the mesoporous structure. The
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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
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essential prerequisite and crucial factor for the actual application as a potential drug
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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
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(BRL-3A). As show in Fig. 6, the SiO2/γ-Fe2O3 composite shows no appreciable
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cytotoxicity against the BRL-3A cells after incubation for 24 h with SiO2/γ-Fe2O3 at
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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
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MTT assay results indicate that the hybrid SiO2/γ-Fe2O3 nanospheres are
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biomedical field.
of the magnetic SiO2/γ-Fe2O3 drug carrier is 16.61 emu/g. After loading Van
drug delivery system decreases to 13.94 emu/g. The diamagnetic contribution of the
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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
they can be separated through exposure to an external magnetic force. The result
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indicates that the SiO2/γ-Fe2O3 nanocomposite can exhibit excellent magnetic
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responsivity and redispersibility in aqueous solution and may find potential
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The FT-IR spectra were performed to validate the composition of the
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SiO2/γ-Fe2O3 and the encapsulation of vancomycin in SiO2/γ-Fe2O3. Fig. 8 presents
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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
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1633 cm-1 are assigned to the stretching vibration of −OH bond and the bending
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vibration of H2O. The result reveals that the −OH groups and H2O are present in
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(960 cm-1), Si−O−Si (1096 cm-1 and 805 cm-1), and Si−O (465 cm-1) are also observed,
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confirming the existence of SiO2. The appearance of the band at 570 cm-1 is ascribed
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to the typical Fe−O stretching vibration of the γ-Fe2O3, indicating that the 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
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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
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validated by the FT-IR spectrum of the free vancomycin (Fig. 8c).
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In this study, vancomycin, an antibiotic, was used as a model drug to investigate
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composite. The drug loading capacity is determined to be 169.3 mg drug/g carrier.
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According to the two equations above, we plotted the release curve for Van in the SBF
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media, as shown in Fig. 9. The Van calibration curve agrees well with the Lambert
where A is the absorbance and C is the concentration of Van in SBF (µg/ml). The
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V t −1
Ccort = Capp + ∑ Capp
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Vt 0
where Ccort is the corrected concentration of released Van at time t, Capp is the
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apparent concentration of released Van of the tested samples, V is the volume of the
It can be seen from Fig. 9 that the Van-SiO2/γ-Fe2O3 drug delivery system
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
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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
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comparison, the in vitro BRL-3A cells viabilities and cumulative vancomycin release
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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
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exhibits good biocompatibility and sustained drug release profile, which are similar to
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that of the SiO2/γ-Fe2O3 sample. Considering the combined advantages of uniform
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particle size, mesoporous structure, good biocompatibility, sustained drug release, and
4. Conclusions
been fabricated by a simple and effective approach. The sample was characterized by
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XRD, SEM, TEM, EDX, XPS, FT-IR, N2 adsorption/desorption isotherms, and MTT
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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
exhibits intense magnetic property and good biocompatibility. Due to the proper
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synthetic strategy may pave a critical way for the design and synthesis of
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incorporating functional nanoparticles into mesoporous structures to exert their
synergistic properties.
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Acknowledgements
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China (21301046, 51302062), Natural Science Foundations of Hebei Province
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(B2017201125, B2017201100, B2016201209), the Second Batch of Top Youth Talent
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2014T70226).
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Figure captions
Fig. 1 XRD patterns of (a) SiO2 and (b) SiO2/γ-Fe2O3 samples. The standard data of
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Fig. 3 (a,b) TEM, (c) HRTEM images, and (d) EDX spectrum of SiO2/γ-Fe2O3
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sample.
Fig. 4 XPS spectra of (a) SiO2/γ-Fe2O3, and (b) O1s, (c) Fe2p, and (d) Si2p for
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SiO2/γ-Fe2O3.
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Fig. 5 N2 adsorption/desorption isotherm of mesoporous SiO2/γ-Fe2O3 sample.
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Fig. 6 In vitro BRL-3A cells viabilities after incubation for 24 h with SiO2/γ-Fe2O3 at
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
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vancomycin.
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Highlights
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● The sample exhibits intense magnetic property and sustained drug release patterns.
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● The nanocomposite may function as a promising targeting drug carrier.
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