Article

Journal of
Copyright 2015 American Scientific Publishers
Nanoscience and Nanotechnology
All rights reserved Vol. 15, 37733779, 2015
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A Facile Way for Fabricating PEGylated Hollow

Mesoporous Silica Nanoparticles and
Their Drug Delivery Application
Xu Teng1
2 , Shan Cheng1
2 , Ran Meng1 , Shuai Zheng1 , Longyan Yang1 , Qian Ma1 ,
Wenguo Jiang1
2
3 , and Junqi He1
2

1
Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
2
Capital Medical University-Cardiff University Joint Centre for Biomedical Research,
Capital Medical University, Beijing 100069, China
3
Metastasis and Angiogenesis Research Group, Department of Surgery, School of Medicine,
Cardiff University, Heath Park, Cardiff, CF14 4XN, U.K.

PEGylated hollow mesoporous silica nanoparticles (HMSN-PEG) were successfully fabricated by

only one simple step through hydrothermal treatment in Na2 CO3 solution. HMSN-PEG nanoparticles
were transformed from conventional PEG-modified mesoporous silica nanoparticles (MSN-PEG).
The as-synthesized HMSN-PEG nanoparticles exhibited higher loading capacity of anticancer drug
(Doxorubicin) Delivered
and betterbysustained
Publishing Technology
release to: Stockholm
property than Library In vitro cell
Universityparticles.
MSN and MSN-PEG
viability of HMSN-PEG IP: nanoparticles
174.26.214.116 On: Wed,
to Hep-G2 cells21was
Octevaluated.
2015 09:13:02
HMSN-PEG nanoparticles
Copyright:
have little in vitro cytotoxicity up to a American Scientific
concentration of 500 Publishers

g/ml. Furthermore, the DOX-loaded
HMSN-PEG nanoparticles exhibited higher cytotoxicity than the DOX-loaded MSN and MSN-PEG
nanoparticles against Hep-G2 cells. Therefore, the HMSN-PEG nanoparticle that generated in this
PEG protecting etching strategy is a promising nanocarrier toward its potential application for cancer
therapy.
Keywords: PEG, Hollow, Mesoporous Silica Nanoparticles, Drug Delivery, Cytotoxicity.

1. INTRODUCTION researchers have focused on the study of HMSN parti-

Mesoporous silica nanoparticles (MSN) have a variety of
unique properties, such as ease of synthesis, high spe-
cific surface area, tunable pore structures, large pore vol-
ume, availability of surface modification, and relatively
stable and homogeneous chemical composition. These fea-
tures endow MSN with many advantages to be applied
in various biomedical applications such as bioimaging,
drug/protein/gene delivery, and biosensor.117 Since Vallet-
Reg and co-workers first reported MCM-41 MSN could
act as nanocarrier for the sustained drug release in 2001,18
more and more reports have been released on MSN as
potential nanocarriers for drug delivery.
Compared to the conventional MSN as nanocarriers
for drug delivery, hollow mesoporous silica nanoparti-
cles (HMSN) exhibit a much higher drug loading capac-
ity because of its huge void space and well-ordered
mesoporous shell pore channel. In the last decade, many
Author to whom correspondence should be addressed.
cles as nanocarriers for drug delivery.1923 For example,
Chen et al. developed a structural difference-based selec-
tive etching strategy to fabricate HMSN, and employed it
for loading anticancer drug (doxorubicin).24 By aid of PVP
as surface protecting agent, Zhang and his co-workers suc-
cessfully fabricate hollow-type MSN, and demonstrated the
unique drug delivery profile by using R6G as a model drug
molecule.25 Similar strategy was also employed by Huang
et al.26 in their study, they also encapsulated the anti-cancer
drug DOX into HMSN particles and evaluated the release
profile in vitro. However, most of HMSN particles that fab-
ricated by the above strategies have a poor dispersity and
biocompatibility, which would decrease the performance of
the drug delivery system due to the limitation of the blood
circulation and targeting therapy efficacy. Therefore, it is
still very important to improve the dispersity and biocom-
patibility of HMSN particles for the improvement of the
therapeutic efficacy of a drug delivery system.

J. Nanosci. Nanotechnol. 2015, Vol. 15, No. 5 1533-4880/2015/15/3773/007 doi:10.1166/jnn.2015.9270 3773

A Facile Way for Fabricating PEGylated Hollow Mesoporous Silica Nanoparticles and Their Drug Delivery Application
It has been reported that the PEGylation can make
nanoparticles to achieve a good dispersity and well
biocompatibility.27
28 Furthermore, many studies on the
PEGylated nanoparticles have demonstrated that the
PEGylation of nanoparticles is one of the most effi-
cient ways to enhance the blood circulation and tumor
2933
cell killing efficacy in vitro and in vivo. There-
fore, some researchers have attempted to PEGylate sil-
ica particles to improve the drug delivery performance
as nanocarriers.34
35 Therefore, it could be believed that
PEGylation of HMSN nanoparticles could improve the
performance of HMSN nanoparticles for drug delivery.
In this study, the PEGylated HMSN nanoparticles
(HMSN-PEG) were successfully fabricated by only one
simple step through hydrothermal treatment in Na2 CO3
solution. HMSN-PEG nanoparticles were well transformed
from PEGylated MSN particles by the selective outer
protection of surface PEG coating. To the best of our
knowledge, this is the first reported strategy for forming
hollow-type MSN particles, simultaneously modifying the
particle surface for improving its biocompatibility. The
drug loading efficiency and release behavior of HMSN-
PEG were investigated by choosing anticancer drug DOX
as a model molecule. The in vitro study of Hep-G2 cells
also proves that the HMSN-PEG has enhanced therapeu-
tic efficacy and no obvious adverse effect on cell via-
bility. In addition, the loading capacity, release profile,
Delivered by Publishing Technology gen
in vitro cytotoxicity, and cellular internalization efficiency
IP: 174.26.214.116 On: Wed,
of HMSN-PEG were also comparedCopyright: with conventional
American Scientific
MSN and MSN-PEG particles.
2. MATERIALS AND METHODS
2.1. Chemicals and Reagents
Cetyltrimethylammonium bromide (CTAB), tetraethyl
orthosilicate (TEOS), sodium carbonate (Na2 CO3 ), ammo-
nia solution (25%28%), 3-aminopropyltriethoxysilane
(APTES), and anhydrous ethanol were obtained from
Beijing Chemical Reagents Company (China). Methoxy-
polyethylene glycol succin- imidyl (mPEG-SC) with
molecular weight of 5 kDa were from Beijing Kaizheng
Biotech Developing Ltd. Beijing, China. Dulbeccos mod-
ified Eagles medium (DMEM) and fetal bovine serum
(FBS) were from Gibco. All reagents were used as
received without further purification unless otherwise
stated.
2.2. Synthesis of PEGylated Hollow
Mesoporous Silica Nanoparticles
Firstly, mesoporous silica nanoparticles (MSN) were
obtained by condensation of tetraethoxysilane (TEOS)
as silica precursor and cetyltrimethylammonium bromide
(CTAB) as template in diluted ammonia aqueous solution
according to the previous reported method.36
37 In a typical
synthesis procedure, 0.1 g CTAB was dissolved in 70 mL
H2 O, and 1 mL NH3 H2 O (25%28%) was added with
3774
Teng et al.
stirring for 15 min at room temperature. 0.6 mL TEOS
was then added with stirring for another 5 h. The products
were isolated by centrifugation, cleaned by four cycles of
centrifugation/washing/redispersion in ethanol, and dried
at 100  C. Then, MSN were obtained after the calcination
of the as-prepared product in air at 550  C for 6 h. Next,
100 mg of MSN was added to 50 mL of ethanol containing
25 L of APTES. After being stirred at room temperature
for 24 h, the mixture was extensively washed with ethanol
and dried at 80  C to obtain the aminated MSN (MSN-
NH2 ) nanoparticles. After resuspended in 50 mL Tris-Cl
buffer (50 mM, pH 8.6), 10 mg mPEG-SC was added, and
then the suspension was stirred for 4 h at 4  C. The result-
ing PEG modified particles (MSN-PEG) were collected
by centrifugation. Finally, 50 mg as-prepared MSN-PEG
were added into 50 mL water solution containing 50 mg
of Na2 CO3 . After the reaction was stirred at 45  C for
12 h, the PEGylated hollow mesoporous silica nanopar-
ticles (HMSN-PEG) were collected by centrifugation and
washed with ethanol and water repeatedly.
2.3. Nanoparticle Characterization
Transmission electron microscope (TEM) images were
obtained using a JEM-2100F electron microscope, oper-
ating at 150 kV. -potential and the mean particle size
were measured using a Malvern Zetasizer 3000HS. Nitro-
adsorptiondesorption
to: Stockholm University measurements
Library were carried out
to 21 Oct 2015
determine the09:13:02
textural properties of silica materials by
using a Publishers
Quantachrome NOVA 4200e surface area ana-
lyzer at 196  C. The prepared products were dried at
300  C before analysis. The pore size distribution plot was
obtained by the BarrettJoynerHalenda (BJH) method.
Fourier transform infrared spectra (FTIR) were recorded
on a Varian Excalibur 3100 spectrometer.
2.4. In Vitro Drug Loading and Release
20 mg of MSN, MSN-PEG, and HMSN-PEG was dis-
persed in a solution of Doxorubicin (DOX) (10 mg/mL
in water) and stirred for 48 h at room temperature, fol-
lowed by centrifugation and washing extensively to obtain
the drug-loaded nanoparticles. The concentration of DOX
was determined by UV/vis spectroscopy measurements
at a wavelength of 480 nm (JASCO V570 spectropho-
tometer). Drug loading amount was calculated according
to the equation of drug loading efficiency (%) = 100
WDOX /WNPsDOX , where WDOX is the weight of DOX
loaded into the NPs and WNPsDOX is the mass of NPs-
DOX. Drug encapsulation rate was calculated accord-
ing to the equation of encapsulation rate (%) = 100
WDOX /WDOX0 , where WDOX is the weight of DOX loaded
into the NPs and WDOX0 is the weight of initially added
DOX. For the drug release assay, the DOX loaded nanopar-
ticles samples were immersed into phosphate-buffered
saline (PBS, pH of 5.0). The mixtures were centrifuged
and the supernatant was extracted at given time intervals.
J. Nanosci. Nanotechnol. 15, 37733779, 2015
Teng et al. A Facile Way for Fabricating PEGylated Hollow Mesoporous Silica Nanoparticles and Their Drug Delivery Application

The releasing concentration of DOX was determined by

UV-vis spectroscopy at 480 nm.

2.5. Cell Culture

Human liver carcinoma cells of Hep-G2 cells (ATCC)
were maintained in DMEM medium containing 10% fetal
bovine serum, 100 U/mL penicillin, and 100 mg/mL strep- Figure 1. Schematic illustration of the formation procedure of PEGy-
tomycin. Cells were cultured with the complete medium lated hollow mesoporous silica nanoparticles.
in 5% CO2 at 37  C. For all experiments, cells were har-
vested from sub-confluent cultures by the use of trypsin
3. RESULTS AND DISCUSSION
and were resuspended in fresh complete medium before
3.1. Preparation of PEGylated Hollow
plating.
Mesoporous Silica Nanoparticles
Figure 1 illustrates the synthesis process of PEGylated hol-
2.6. Cell Viability Assay
low mesoporous silica nanoparticles (HMSN-PEG). Meso-
In vitro cytotoxicity of MSN, MSN-PEG, and HMSN-PEG
porous silica nanoparticles (MSN) with ordered structure
nanoparticles was assessed using 3-[4,5-dimethylthiazol-
were prepared first. Then, the PEGylated MSNs (MSN-
2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. 1000
PEG) were fabricated by grafting PEG molecules with
cells were seeded in 96-well plates for 24 h to allow the
surface aminated MSN (MSNNH2 ) nanoparticles. When
cells to attach and then exposed to the serial concentrations
these MSN-PEG particles were treated by Na2 CO3 solu-
of MSN, MSN-PEG, and HMSN-PEG nanoparticles in 5%
 tion in the presence of PEG molecules as surface coatings,
CO2 at 37 C. After 24 h incubation, the medium contain-
the HMSN-PEG particles with typical hollow void space
ing nanoparticles was removed, and 200 L of MTT solu-
tion (diluted in a culture medium with a final concentration were successfully prepared.
of 1 mg/mL) was added and incubated for another 4 h. The From TEM images of MSN, MSN-PEG, HMSN-PEG
medium was then replaced with 200 L of dimethyl sul- particles in Figure 2, all three types of nanoparticles (NPs)
foxide (DMSO), and the absorbance was monitored using are spherical morphology and well ordered. HMSN-PEG
a microplate reader at aDelivered
wavelength has a hollow structure according to the noticeable contrast
byofPublishing
570 nm. The cyto-
Technology to: Stockholm University Library
IP: 174.26.214.116
toxicity was expressed as the percentage On: Wed, 21 Oct 2015 09:13:02shell of the nanoparticles under
of cell viability between the core and the
compared to the untreated control cells.Copyright: American TEM observation.
Scientific PublishersFurthermore, it can also be observed

2.7. In Vitro Cytotoxicity of DOX-Loaded

Nanoparticles
Hep-G2 cells were seeded in a 96-well plate at a density
of 1000 cells per well and cultured in 5% CO2 at 37  C for
24 h. Then, free DOX, DOX-loaded MSN nanoparticles,
DOX-loaded MSN-PEG nanoparticles, and DOX-loaded
HMSN-PEG nanoparticles were added to the medium at
a DOX concentration of 5 g/mL, and the cells were
incubated in 5% CO2 at 37  C for 6 h, and then the
cells were washed carefully with PBS to remove DOX
or DOX-loaded nanoparticles nanoparticles. Subsequently,
one serial samples were used to measure cell viability by
MTT assay, and the other serial samples were incubated
in the culture media for 24 h, after that, cell viability was
measured by MTT assay.

2.8. Fluorescent Observation of

Cellular Internalization
For observing the drug concentration, the Hep-G2 cells
were seeded on glass-bottom dishes (35 mm, MatTek Cor-
poration). A final drug concentration of 5 g/mL nanopar-
ticles was added to the cells and incubated for 4 h. The
cells were washed twice with PBS and then micrographs
were taken on a Nikon fluorescence microscope (Nikon
Eclipse TiS, CCD: Ri1).
Figure 2. TEM images of mesoporous silica nanoparticles (A), PEGy-
lated mesoporous silica nanoparticles (B), PEGylated hollow mesoporous
silica nanoparticles with 6 h treatment under 45  C hydrothermal treat-
ment in Na2 CO3 solution (C), and PEGylated hollow mesoporous silica
nanoparticles with 12 h treatment under 45  C hydrothermal treatment in
Na2 CO3 solution (D).

J. Nanosci. Nanotechnol. 15, 37733779, 2015 3775

A Facile Way for Fabricating PEGylated Hollow Mesoporous Silica Nanoparticles and Their Drug Delivery Application Teng et al.

that ordered mesopores are distributed on the shells when

MSN-PEG particles treated in Na2 CO3 solution for 6 h at
45  C (Fig. 2(C)). After 12 h hydrothermal treatment, well
hollow nanoparticles were formed (Fig. 2(D)). In the fol-
lowing experiments, HMSN-PEG with 12 h hydrothermal
treatment at 45  C in Na2 CO3 solution was used.
Particle size distributions of MSN, MSN-PEG, HMSN-
PEG nanoparticles in aqueous solution measured by
dynamic light scattering (DLS) are shown in Figure 3(A).
Hydrodynamic particle sizes of MSN, MSN-PEG, HMSN-
PEG are 89 12 nm, 105 17 nm, 101 11 nm, respec-
tively. It can be observed that the size of MSN was slightly
increased after PEGylation. However, the size difference
between MSN-PEG and HMSN-PEG was not obvious. Figure 4. FTIR spectras of MSN, MSN-PEG, HMSN-PEG
In addition, the PEGylation could improve the dispersity nanoparticles.
of MSN-PEG and HMSN-PEG in PBS solution. After
MSN, MSN-PEG, HMSN-PEG nanoparticles solution in corresponding to the stretching vibrations of C H group,
PBS were statically placed for 24 h, almost all MSN parti- the bending vibration of C H group, and the deformation
cles were located in the bottom, while most of MSN-PEG vibration of CH3 group, respectively. Meanwhile, these
and HMSN-PEG particles still suspended in PBS solution peaks were not observed in MSN particles. These results
(Data not shown). Therefore, the PEGylation enhances the indicate that PEG molecules were successfully grafted
dispersity and stability of HMSN nanoparticles in aque- onto the surface of particles, and no obvious fall-off of
ous condition. Figure 3(B) shows zeta potentials of MSN, PEG molecules happened during the hydrothermal treat-
MSN-PEG, HMSN-PEG nanoparticles in H2 O. It can be ment for obtaining HMSN-PEG.
found that zeta potentials are changed after the PEGyla- Pore size of MSN, MSN-PEG, HMSN-PEG nanopar-
tion of MSN. However, there is no obvious change for ticles was determined by N2 adsorptiondesorption mea-
HMSN-PEG during transformation
Delivered byfrom MSN-PEG.
Publishing The
Technology surement
to: StockholmusingUniversity
BJH (BarrettJoynerHalenda)
Library method
zeta potential of MSN is 351 46 mV, while it is (Fig. 5). It could
IP: 174.26.214.116 On: Wed, 21 Oct 2015 09:13:02 clearly see that the particle size of MSN
45 17 mV for MSN-PEG and 58 Copyright:
23 mV for American (2.51 nm)Publishers
HMSN- Scientific was slightly decreased to 2.37 nm after PEGy-
PEG particles. This suggests that PEG molecules have lation, which may be induced by the masking of PEG
been grafted on MSN particles and changed the surface molecules. And hydrothermal treatment of MSN-PEG in
potential, but the hydrothermal treatment has no significant Na2 CO3 solution could enlarge the pore size to 3.05 nm,
effect. this may be probably caused by the corrosion of base.
Here, FTIR spectra were used to further confirm the
PEGylation of MSN particles. As shown in Figure 4, there 3.2. Formation Mechanism of HMSN-PEG
was a strong absorption peak at 1091 cm1 for all the three To investigate the formation mechanism of HMSN-PEG,
types of nanoparticles, which is assigned to the asym- time-dependent experiments were carried out. The synthe-
metric stretching vibrations of the Si O Si from silica sis process of HMSN-PEG at different reaction time was
NPs.38 MSN-PEG and HMSN-PEG particles showed dis- monitored and characterized by TEM. At the beginning
tinct peaks at around 29602850, 1470, and 1350 cm1 , stage of the reaction, the inner core of MSN begun to

Figure 3. (A) Hydrodynamic particle size and (B) Zeta potentials of different types of silica nanoparticles dispersed in aqueous solution.

3776 J. Nanosci. Nanotechnol. 15, 37733779, 2015

Teng et al. A Facile Way for Fabricating PEGylated Hollow Mesoporous Silica Nanoparticles and Their Drug Delivery Application

Figure 5. The pore size of MSN, MSN-PEG, HMSN-PEG, by N2 Figure 8. Cell viabilities of MSN, MSN-PEG, HMSN-PEG nanoparti-
adsorptiondesorption measurement. cles to Hep-G2 cells measured by MTT assay.

without any surface coatings. As shown in Figure 6, in the

absence of PEG coating, the outer of MSN were almost
etched away and the resulting particles displayed. This
observation indicated that PEG molecules in the reaction
system protect the particle shell from etching by Na2 CO3 .
Therefore, in our study, the PEG plays important roles in
protecting the particle shell from etching and selectively
Figure 6. TEM images of MSN with 6 h treatment under 45  C etching silica inner cores by Na2 CO3 to form HMSN-PEG
hydrothermal treatment in Na2 CO3 solution (A), and MSN with 12 h from MSN-PEG particles.
treatment under 45  C hydrothermal treatment in Na2 CO3 solution (B).
Delivered by Publishing Technology3.3.
to: Stockholm University
In Vitro Drug LoadingLibrary
and Release
IP: 174.26.214.116 On:
dissolve, which was etched by Na2 CO3 . As is shown in Wed, 21 Oct 2015 09:13:02
To determine the
Copyright: American Scientific Publishers drug delivery efficiency of MSN, MSN-
Figure 2(C), MSN-PEG particles started to transform and PEG, HMSN-PEG particles as nanocarriers, doxorubicin
a void space was appeared. However, the smooth and reg- hydrochloride (DOX), an anticancer drug, was used to
ular border of MSN-PEG was still existed. As the etching load into these three types of nanoparticles. DOX load-
time is prolonged to 12 h, a well-organized hollow struc- ing contents in MSN, MSN-PEG, HMSN-PEG particles
ture was formed (Fig. 2(D)). Based on the observation of were 268.3 mg, 215.7 mg, and 380.9 mg DOX per 1 g
the etching experiments, one important issue was proposed of nanoparticles, respectively (Fig. 7(A)). We could see
during the formation of HMSN-PEG, i.e., the surface coat- clearly that HMSN-PEG showed obvious higher loading
ing of PEG molecules as a protection layer assisted the capacity than MSN and MSN-PEG particles, which may
forming of hollow particles. To understand the important be induced by the slightly enlarged pore size by base treat-
role of PEG in the formation of HMSN-PEG, comparative ment (Fig. 3(A)). Here, MSN-PEG particles exhibit a lit-
experiments were carried out by etching MSN particles tle lower DOX loading capacity than MSN nanoparticles,

Figure 7. (A) DOX loading capacity of MSN, MSN-PEG, HMSN-PEG nanoparticles. (B) The cumulative drug release profile of DOX from MSN,
MSN-PEG, HMSN-PEG nanoparticles in PBS (pH = 5) at 37  C.

J. Nanosci. Nanotechnol. 15, 37733779, 2015 3777

A Facile Way for Fabricating PEGylated Hollow Mesoporous Silica Nanoparticles and Their Drug Delivery Application
Figure 9. Cell viabilities against free DOX, DOX-loaded MSN, MSN-
PEG, and HMSN-PEG nanoparticles at a DOX concentration of 5 g/mL.
which may be attributed to the positively charged DOX
molecules more easily transport in mesopores and are
bonded to the negatively charged MSN nanoparticles.39
The release profile of DOX from the DOX-loaded MSN,
MSN-PEG, HMSN-PEG particles in PBS (pH 5) at 37  C
is shown in Figure 7(B). All three types of nanoparti-
cles exhibited the typical sustained release behavior. A fast
release happened within the first 12 h, followed by a rel-
atively slow release rate until the end of assay (Up to
96 h duration). In addition, it can be
Delivered byfound that theTechnology
Publishing release
rate of HMSN-PEG nanoparticles IP: within
174.26.214.116 On: Wed,
96 h is almost
always faster than that of MSN and MSN-PEG Copyright:nanoparti-
American Scientific Publishers
cles. For HMSN-PEG nanoparticles, the amino groups and
the slightly larger pore size in the mesoporous channels
induce DOX molecules into channels to fast encapsulate,
but the slower diffusion of DOX molecules from hollow
cores to outside by the aid of amino groups and surface
PEG coating.
3.4. Cell Viability
After proving the superior advantages of HMSN-PEG
on the drug loading capacity and sustained release, the
cell viability of MSN, MSN-PEG, HMSN-PEG on Hep-
G2 cells was evaluated by MTT assay. Figure 8 shows
the effects of MSN, MSN-PEG, HMSN-PEG particles
on cell viabilities of Hep-G2 cells. It can be seen that
both two PEGylated particles, MSN-PEG and HMSN-
Figure 10. Fluorescence microscopy images showing the internalization of MSN-DOX (A), MSN-PEG-DPX (B), and HMSN-PEG-DOX (C).
3778
Teng et al.
PEG, have little cytotoxicity to cells up to a concentration
of 500 g/mL. Only a little decrease of cell viability of
MSN-PEG and HMSN-PEG particles with increasing the
concentration of nanoparticles, but only 75% of cell via-
bility of MSN particles was kept at the concentration of
500 g/mL. This demonstrated that surface PEGylation
could effectively improve the biocompatibility of MSN,
and PEGylated particles are more suitable as vehicles for
drug delivery.
To order to verify DOX delivery efficacy of MSN,
MSN-PEG, HMSN-PEG particles, the cytotoxic effects
of the DOX-loaded nanoparticles on Hep-G2 cells were
tested. Hep-G2 cells were incubated in DMEM culture
media containing free DOX, DOX-loaded MSN, MSN-
PEG and HMSN-PEG particles for 6 h, and then Hep-G2
cells were washed carefully with PBS to remove free DOX
or DOX-loaded nanoparticles. Subsequently, one serial
samples were used to measure cell viability by MTT assay,
and the other serial samples were incubated in DMEM
culture media for 24 h, followed by measure cell via-
bility. Figure 9 shows cell viabilities against free DOX,
DOX-loaded MSN, MSN-PEG, HMSN-PEG particles at a
DOX concentration of 5 g/mL. Free DOX, DOX-loaded
nanoparticles have great cytotoxicities to Hep-G2 cells. It
also can be observed that the cytotoxicities of free DOX,
DOX-loaded nanoparticles are close to each other after
6 h incubation, but the DOX-loaded HMSN-PEG parti-
to: Stockholm
cles University
exhibit somewhat Library
greater cytotoxicity than free DOX,
21 Oct 2015 09:13:02
DOX-loaded MSN, and DOX-loaded MSN-PEG for 24 h
incubation. Therefore, the PEGylated HMSN nanoparticles
as drug delivery vehicles can enhance the drug delivery
efficacy and tumor cell killing efficacy.
3.5. In Vitro Cellular Internalization
Efficient cellular uptake of nanoparticles is necessary for
intracellular drug delivery and efficient therapy. To monitor
the internalization efficiency of DOX-loaded nanoparticles
by Hep-G2 cells, fluorescent microscopy was employed.
As shown in Figure 10, Hep-G2 cells were incubated with
DOX-loaded nanoparticles at a final drug concentration of
5 g/mL for 4 h. It can be observed that red emitting
points are distributed in cells and on the surface of cells for
all the three types of DOX-loaded nanoparticles. In addi-
tion, the Hep-G2 cells treated by DOX-loaded HMSN-
PEG particles were obviously sparse when compared to
J. Nanosci. Nanotechnol. 15, 37733779, 2015
Teng et al. A Facile Way for Fabricating PEGylated Hollow Mesoporous Silica Nanoparticles and Their Drug Delivery Application
cells treated by DOX-loaded MSN and DOX-loaded MSN-
PEG particles. These results could also confirm that the
DOX-loaded HMSN-PEG particles could facilitate the cell
uptake and thus generate more Hep-G2 cells death. There-
fore, HMSN-PEG particles could enhance the performance
of drug delivery vehicles as compared to conventional
MSN, MSN-PEG particles.
4. CONCLUSIONS
In conclusion, we have developed a new selective etch-
ing strategy to synthesize HMSN-PEG particles through
simple hydrothermal treatment using PEG as surface pro-
tecting layer. PEG molecules play significant roles in
forming hollow-type MSN particles, simultaneously mod-
ify the particle surface for improving its biocompatibil-
ity. Drug delivery of anti-cancer drug DOX showed that
these HMSN-PEG particles have a high drug loading
capacity and exhibit sustained release of drug compared
with conventional MSN and MSN-PEG due to their huge
void space and more hierarchically mesoporous structures.
HMSN-PEG particles have little in vitro cytotoxicity to
Hep-G2 cells up to a concentration of 500 g/mL, and the
DOX-loaded HMSN-PEG nanoparticles exhibited a little
higher cytotoxicity than DOX-loaded MSN and MSN-PEG
particles against Hep-G2 cells. Therefore, given the versa-
tility of this strategy, it will have great potential to fabricate
multifunctional hollow Delivered
spheres with bywell
Publishing Technology to: and
biocompatibility
and high loading capacity towardIP: 174.26.214.116
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applications for drug delivery, targeting, Copyright:
MRI imaging American
and Scientific
hyperthermia for cancer therapy.
Acknowledgment: This work was supported by the
National Natural Science Foundation of China (NSFC)
(Nos. 81272887, and 81141033), Beijing Municipal Nat-
ural Science Foundation (No. 7131003). The authors
thank Professor Fangqiong Tang, Professor Laifeng Li, Dr.
Xinglu Huang, and Dr. Nanjing Hao (Technical Institute
of Physics and Chemistry, Chinese Academy of Sciences)
for their kindly discussion and useful suggestion.
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Received: 5 November 2013. Accepted: 6 December 2013.
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