Materials Letters 211 (2018) 32–35
Contents lists available at ScienceDirect
Materials Letters
journal homepage: www.elsevier.com/locate/mlblue
MIL-101/CDs/MIL-101 for potential fluorescence imaging and pHresponsive drug delivery
Yana Liu 1, Lu Fan 1, Chen Xu, Keke Sun, Zhennan Shi ⇑, Ling Li ⇑
Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Hubei University, 430062, People’s Republic of China
Ministry-of-Education Key Laboratory for the Synthesis and Application of Organic Function Molecules, Hubei University, 430062, People’s Republic of China
a r t i c l e
i n f o
Article history:
Received 8 June 2017
Received in revised form 29 August 2017
Accepted 21 September 2017
Available online 21 September 2017
Keywords:
Functional
Composite materials
Fluorescence
Drug delivery
a b s t r a c t
A composite MIL-101/CDs/MIL-101 comprising MIL-101 and carbon quantum dots (CDs) was prepared
and characterized. The particles were uniform in size and found to be potentially used for fluorescence
imaging. Cytotoxicity assays indicated the particles were biocompatible and suitable for carrying drugs.
In the drug release experiments, the MIL-101/CDs/MIL-101 demonstrated an excellent pH-triggered drug
release.
Ó 2017 Elsevier B.V. All rights reserved.
1. Introduction
A main challenge for cancer therapy is to develop functional
drug carriers which were able to release drugs simultaneously
when diagnosis [1]. Fluorescence imaging (FOI) could be used for
diagnosis with high sensitivity and suitability for visual observation of living cells. There are several choices on materials as FOI
contrast agent, such as rare earth elements and fluorescent dyes
[2,3], but most of these fluorescent materials are not suitable for
cell and tissue imaging due to their potential side effect to human
bodies. Carbon quantum dots (CDs) have been attracting increasing
attention for the dependent photoluminescence and high compatibility. On the other hand, the pH value is 5.5–5.8 in cancer cells,
which is lower than pH 7.4 of normal cells, then, pH-responsive
was necessary in order to minimize the side effects [4]. MIL-101,
with Fe3+ as central ion and terephthalic acid as ligand, could be
used for drug delivery for its good biocompatibility and pHresponsiveness [4]. Therefore, combination CDs and MIL-101 to
form composites were able to achieve fluorescence imaging and
drug delivery simultaneously. A sandwich structure was able to
influence the activity of the entire nanoparticle surface [5], and it
will be hopeful in excellent stability and high drug loading. Thus,
⇑ Corresponding authors at: Hubei Collaborative Innovation Center for Advanced
Organic Chemical Materials, Hubei University, 430062, People’s Republic of China
(Z. Shi and L. Li).
E-mail addresses: pachelbel_4ever@163.com (Z. Shi), waitingll@yahoo.com (L. Li).
1
These authors contributed equally to this work.
https://doi.org/10.1016/j.matlet.2017.09.073
0167-577X/Ó 2017 Elsevier B.V. All rights reserved.
sandwiching nanoparticles MIL-101/CDs/MIL-101 were prepared
in this study.
2. Experimental
2.1. Chemicals and materials
Glucose, terephthalic acid (H2BDC, 98%), Ferric trichloride
hexahydrate (FeCl36H2O, 99.0%), Ethylene glycol, Sodium acetate
trihydrate
(CH3COONa),
polyvinylpyrrolidone
(PVP),
N,
N-dimethylformamide (DMF) were purchased from Aladdin
Industrial Corporation. Doxorubicin (DOX) was purchased from
Sinopharm (Shanghai) Chemical Reagent Co., Ltd., China. All other
chemicals used in this work were of analytical grade.
2.2. Preparation of MIL-101/CDs/MIL-101
0.24 g glucose was totally dissolved in 30 mL water and heated
to 160 °C for 24 h in a Teflon. After cooling to room temperature,
dialysis for 24 h, then the CDs solution was transferred to a
50 mL volumetric flask for use. MIL-101 was synthesized by a
hydrothermal method as reference [6]. 0.2 g MIL-101 was dissolved in 10 mL N,N-dimethylformamide (DMF), 5 mL CDs solution
was slowly added. stirred for 2 h at room temperature. Washed by
ethanol and water 3 times respectively, MIL-101/CDs was obtained
and dissolved in 4 mL, then 1.8 mL precursor solution was added
and heated to 120 °C for 8 h in a 50 mL Teflon. The precipitate
was collected and washed by ethanol and water for 3 times, and
Y. Liu et al. / Materials Letters 211 (2018) 32–35
MIL-101/CDs/MIL-101 was obtained. 27.0 mg FeCl36H2O, 16.6 mg
and 6 mg polyvinylpyrrolidone (PVP) were totally dissolved in
3 mL DMF to prepare the precursor solution.
2.3. Materials characterization
Powder X-ray diffraction (XRD) patterns were performed on a
Japanese Rigaku D/MAX-IIIC-ray diffractometer with the 2h range
of 5–80°. Fourier transform infrared spectroscopy (FTIR) analysis
was conducted on a Perkin Elmer Spectrum one Fourier Transform
Infrared spectrometer. The morphology of the MIL-101 and
MIL-101/CDs/MIL-101 was examined by transmission electron
microscopy (TEM, JEOL1010, Japan) at an accelerating voltage of
100 kV. DOX in solution were determined using an ultraviolet
spectrophotometer (Varian Cary 4000, USA) at 460 nm. The calibration curve was obtained from the spectra of standard solutions.
2.4. Cell viability studies
The MCF-7 cells were cultured with MIL-101/CDs/MIL-101
(concentrations from 0 lg/mL to 150 lg/mL) in a 96-well plate in
a final volume of 150 ml with 20,000 cells per well for 24 h. The
MTS (20 mL) was added into each well and incubated for 4 h. After
shaking the plate briefly on a shaker the adsorbent of treated and
untreated cells was measured using a plate reader at 490 nm.
Untreated cells in medium were used as controls.
2.5. In vitro loading and release of DOX
100 mg MIL-101/CDs/MIL-101 was added to 20 mL of 100 mg/L
DOX water solution at room temperature and shaken for 24 h
under dark conditions. The DOX-loaded MIL-101/CDs/MIL-101
was centrifuged and washed with water to remove the excess
DOX, and then dried in a vacuum drier. For the experiments of
the release of DOX, 10 mg of DOX-loaded MIL-101/CDs/MIL-101
33
was suspended in 100 mL of PBS (pH 5.5 and pH 7.4). Both samples
were gently shaken at 37 °C under dark conditions. At scheduled
times, 3 mL of the solution was withdrawn for analysis by UV–
vis absorption spectroscopy at a wavelength of 460 nm and
replaced with the same volume of fresh buffer solution.
3. Results and discussion
3.1. Characterization of MIL-101/CDs/MIL-101
The TEM images of MIL-101, CDs and MIL-101/CDs/MIL-101
were shown in Fig. 1(a0 –d0 ). It was clear that the morphology of
MIL-101 (Fe) is an octahedral structure with uniform size, which
was consistent with the SEM images. Fig. 2(b) showed CDs were
uniform particles with 3 nm. As for MIL-101/CDs/MIL-101, there
was crystal packing structure, as seen in Fig. 1(c0 ) and (d0 ). It could
be explained by the interpenetration of MIL-101 crystals. CDs particles were too small to be found in the images.
Fig. 2(a) showed the X-ray diffraction patterns of MIL-101 and
MIL-101/CDs/MIL-101. The diffraction peaks of MIL-101 were in
accordance with the reported literature [6], and the diffraction
peaks of MIL-101/CDs/MIL-101 were similar to those of MIL-101,
it could be explained that the amorphous structure of carbon quantum dots had not characteristic peak. Fig. 2(b) showed the infrared
spectra of the two samples are very similar, which was caused by
the same functional groups. The peaks at 500 cm1–800 cm1
were the bending vibration bands of Benzene, and peaks at
1556 cm1–1371 cm1 were the symmetric stretching of carboxyl
groups. There was an obvious difference at 3300–3500 cm1. The
peak at 3500 cm1 was attributed to the hydroxyl groups of MIL101. But for MIL-101/CDs/MIL-101, there was a broad peak at
3300 cm1. It can be explained by the association of hydroxyl
groups because there were a large number of hydroxyl and carboxyl groups in CDs, which further proved the presence of CDs
on the composites.
Fig. 1. TEM images (a–d). (a) MIL-101; (b) CDs; (c, d) MIL-101/CDs/MIL-101.
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Y. Liu et al. / Materials Letters 211 (2018) 32–35
Fig. 2. XRD (a), FTIR (b), fluorescence spectra (c) and drug loading (d).
Fig. 3. Cell viability and pH responsive release of MIL-101/CDs/MIL-101.
Fig. 2(c) showed fluorescence spectrum of CDs and MIL-101/
CDs/MIL-101 with 410 nm excitation. It can be observed that there
was an emission peak at 442 nm of CDs. As for MIL-101/CDs/MIL101, there were two emission peaks at 430 nm and 485 nm. The
blue shift of the fluorescence peak of CDs could be explained by
the rigidifying fluorescent linkers of MIL-101 in the formation of
the composite [7]. Besides, the new peak at 485 nm may originate
from the conjugated effect of terephthalic acid in MIL-101. Because
the excellent fluorescence properties, MIL-101/CDs/MIL-101was
hopeful to be used for fluorescence imaging.
Dox was selected as drug model and the drug loading of CDs
and MIL-101/CDs/MIL-101 was compared, as shown in Fig. 2(d).
It was clear that the drug loading of MIL-101/CDs/MIL-101 was larger than that of CDs. It could be explained by the unique structure
of MIL-101/CDs/MIL-101, with more porous units in the materials.
So MIL-101/CDs/MIL-101 was more suitable for drug carrier
because of its high drug loading.
The cytotoxicity of MIL-101/CDs/MIL-101 was then tested, and
the result was shown in Fig. 3(a). MCF-7 cells were incubated with
different concentration of MIL-101/CDs/MIL-101 (0, 25, 50, 100,
150 lg/mL). It was clear that cellular viability were all greater than
85%, indicating the low cytotoxicity of MIL-101/CDs/MIL-101, thus
can be used as a vehicle for drug delivery. DOX was selected as a
drug model and the drug release in PBS buffer solutions at pH
7.4 and pH 5.5 was shown in Fig. 3(b). The cumulative DOX release
reached only 38% after 32 h at pH 7.4. However, the release of DOX
at pH 5.5 was significantly faster and reached 100% after 32 h. It
can be seen that the release of DOX is strongly pH-dependent.
Y. Liu et al. / Materials Letters 211 (2018) 32–35
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4. Conclusion
References
In summary, MIL-101/CDs/MIL-101 was successfully prepared.
The experimental results confirmed the formation of MIL-101/
CDs/MIL-101, excellent fluorescence properties and excellent
pH-responsive release behavior. In addition, cytotoxicity tests
demonstrated that the MIL-101/CDs/MIL-101 are highly biocompatible. It can be concluded that MIL-101/CDs/MIL-101 have great
potential for fluorescence imaging and pH-responsive drug delivery of DOX.
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Acknowledgments
This work was supported by The National Natural Science Foundation of China (51302071) and Wuhan Morning Light Plan of
Youth Science and Technology (2017050304010282).