Synthesis of light-controlled superparamagnetic core-shell structured nanocomposite for drug delivery

Article abstract of DOI:10.1166/jnn.2017.13749

This paper reported a core-shell structured site-specific light-controlled magnetic nanocomposite for drug delivery. Its core was composed of superparamagnetic Fe₃O₄ nanoparticles for magnetic guiding purposes. Its outer shell consisted of mesoporous silica molecular sieve MCM-41 which offered highly ordered hexagonal tunnels for drug molecules. A ligand N1-(5H-cyclopenta [1,2-b:5,4-b′] dipyridin-5-ylidene) benzene-1,4-diamine (denoted as Dafo-Ph-NH₂) was coupled to the MCM-41shell. The Dafo end can flip over under 510 nm light therefore will act as a light stimulated acceptor. The final composite was analyzed by electron microscope images, XRD, IR spectra, thermogravimetry, MTT and N₂ adsorption/desorption.Our Dafo-MCM-41@Fe₃O₄ composite shows light controlled release property for vitamin B₁₂ in vitro.

Full text of DOI:10.1166/jnn.2017.13749

Article
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Nanoscience and Nanotechnology
Vol. 17, 4524–4531, 2017
Copyright © 2017 American Scientific Publishers
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Printed in the United States of America
Synthesis of Light-Controlled Superparamagnetic
Core–Shell Structured Nanocomposite for Drug Delivery
Tieyu Chen1ꢀ2ꢀ∗ꢀ†, Tianming Huang1ꢀ†, and Henry Dai2
1Guangxi Medical University, Nanning 530021, Guangxi, China
2Department of Chemistry, University of Calgary, Calgary, Alberta, T2N 1N4, Canada
This paper reported a core–shell structured site-specific light-controlled magnetic nanocomposite
for drug delivery. Its core was composed of superparamagnetic Fe3O4 nanoparticles for magnetic
guiding purposes. Its outer shell consisted of mesoporous silica molecular sieve MCM-41 which
offered highly ordered hexagonal tunnels for drug molecules. A ligand N1-(5H-cyclopenta [1,2-
b:5,4-bꢀ] dipyridin-5-ylidene) benzene-1,4-diamine (denoted as Dafo-Ph-NH2ꢀ was coupled to the
MCM-41shell. The Dafo end can flip over under 510 nm light therefore will act as a light stimu-
lated acceptor. The final composite was analyzed by electron microscope images, XRD, IR spectra,
thermogravimetry, MTT and N2 adsorption/desorption. Our Dafo-MCM-41@Fe3O4 composite shows
light controlled release property for vitamin B12 in vitro.
Keywords: Fe3O4 Core, Drug Delivery, Biocompatibility, B12 Adsorption, Site-Specific,
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Nanocomposite.
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1. INTRODUCTION
release as less as possible to avoid the side effects. For the
past few years, mesoporous and nanoporous silica based
systems for drug delivery, controlled release, and bioseper-
ation have attracted numerous interests. The plenty silanol
groups on the surface for modification, which provides
a strong frame work for deposition and incorporation
of guest molecules to give multifunctional capabilities.
Therefore various candidates have been synthesized to be a
controlled drug delivery system due to their highly specific
surface area, well-ordered pores and large pore volumes.3–8
A few researchers realized their drawback of the traditional
modified mesoporous silicon drug carriers, it is nearly
impossible to request a site-specific release from them.
Thus, it is needed to explore and develop smart deliv-
ery systems with both controllable release and site-specific
character, and proposed Core–shell structured nanocom-
posites to meet the above requirements.9ꢀ10 However, the
modification on controllable and active release is rarely
seen. Thus, in this effort, we try to construct a compos-
ite with the two properties: site-specific delivery, and light
controlled smart release. To obtain the above properties,
we synthesized a composite where Fe3O4 and MCM-41
are applied as inner core and outer shell, respectively. An
organic ligand was grafted into MCM-41 tunnels aiming
at releasing drug under light stimulating. This magnetic
Vitamin B12 plays a significant role in hematopoiesis,
DNA synthesis, cell metabolism and maintains the func-
tion of nerve system. To the human, vitamin B12 can be
mainly obtained from the animal derived foods, and its
digestive absorption needs the help of gastric acid and
intrinsic factor. Vegetarian, atrophic gastritis patients lack-
ing of gastric acid and gastrointestinal diseases patients
lacking of intrinsic factor are prone to vitamin B12 defi-
ciency, and this should lead to further diseases such as
pernicious anemia, methylmalonic academia, deprementia,
subacute combined degeneration, hyperhomocystinemia,
vascular dementia and Alzheimer disease.1ꢀ2 Oral admin-
istration is the simplest method to treat the vitamin B12
deficiency. However the absorption process is slow and
quite inefficient. Therefore, developing a new controlled
release material is a hot-spot in the application research
on Vitamin B12.
An ideal drug carrier should have enough capacity of
holding drug molecules and the ability to release them at
specific tissues, organs on specific time or concentration.
Before getting to the morbid tissues, drug carrier should
∗Author to whom correspondence should be addressed.
†These two authors contributed equally to this work.
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Chen et al.
Synthesis of Light-Controlled Superparamagnetic Core–Shell Structured Nanocomposite for Drug Delivery
nanocomposite is further considered and evaluated for site-
specific and controlled release drug delivery.
2.3. Construction of BPTS-MCM-41@Fe3O4
The core–shell supporting matrix BPTS-MCM-41@Fe3O4
was prepared in a four-step procedure as following. First,
the magnetic nanoparticles Fe3O4 core was synthesized
with FeCl3 ·6H2O as starting material.12ꢀ13 To 150 mL gly-
col was added FeCl3 ·6H2O (4 g), SDS (1.5 g) and NaAc
(11 g). The mixture was held still at room temperature for
30 min then transferred to a teflon flask. Tꢁhis flask was
sealed into an autoclave and heated to 200 C overnight.
After cooled to room temperature, the solid product was
filtered and rinsed by distilled water. Then this magnetic
nanoparticle core was coated with amorphous silica. To
200 mL ethanol, 1 g Fe3O4 was added, kept stirring under
ultrasonics for 20 min, then added another 150 mL ethanol,
75 mL deionized water, 5 mL ammonia and 2 g TEOS.
This mixture was further stirred at room temperature for
5 hours then centrifuged. Crude product (SiO2@Fe3O4ꢃ
was collected and washed with distilled water.
Silica molecular sieve MCM-41 was further planted
on SiO2@Fe3O4 following below steps. To a solution
of 160 mL deionized water, 120 mL ethanol and 5 mL
ammonia, was added SiO2@Fe3O4 (1 g), CTAB (0.8 g).
The mixture was stirred under ultrasonics for 15 min-
utes. Then TEOS (2 g) was added at drop-wise into
the suspension and allowed to react at room temperature
overnight. Quenched the reaction by centrifugation. Then
dispersed the solid compound again with 300 mL ethanol
2. EXPERIMENTAL DETAILS
2.1. Reagents and Instruments Information
Starting chemicals of this work are listed below.
1,10-phenanthroline, benzene-1,4-diamine, KOH, KMnO4,
tetraethoxysilane (TEOS, AR), odium dodecyl sulfate
(SDS, AR), cetyltrimethylammonium bromide (CTAB,
AR), FeCl3 (AR), p-toluene sulfonic acid, (3-Bromo-
propyl)trimethoxysilane (BPTS, AR), NH3 ·H2O (28 wt%),
vitamin B12 and concentrated HCl were all bought from
Sigma-Aldrich. Organic solvents used in this work, such as
anhydrous ethanol, toluene, glycol, CHCl3, n-hexane (AR)
and tetrahydrofuran (THF), were purchased from Sigma-
Aldrich. Solvent water was deionized.
Equipment information is summarized as follows.
A
Perkin-Elmer Spectrum 100 FTIR spectrometer
(400–4000 cm−1
,
KBr pellet technique), a Bruker
AVANCE 300 spectrometer, and an Agilent 1100 MS
series/AXIMA CFR MALDI/TOF MS spectrometer were
used to record IR, NMR and MS spectra, respectively.
Magnetic property was obtained from a MPM5-XL-5
superconducting quantum interference device. XRD mea-
surement was performed by a Rigaku Multiflex X-ray
diffractometer (ꢁ = 1ꢂ5418 Å). N2 adsorption and desorp-
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tion measurement was taken with a Nova l000 analyzer,
and 20 mL HCl. This mixture was stirred at room tempera-
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Pore size and volume were calculated by Barrett–Joyner–
Halenda (BJH) model. Sample morphology was recorded
with a Hitachi S-4800 microscope and a JEOL JEM-
2010 transmission electron microscope, respectively. Sam-
ple thermal degradation was analyzed by a Perkin-Elmer
STA 6000 thermal analyzer. Vitamin B12 concentrations
were recorded through a LAMBDA 25 UV/Vis spec-
trophotometer. The OD reading in the cytotoxicity testing
was obtained via a Beckman DTX 880 microplate reader
at a wavelength of 595 nm. Above operations were carried
out in the air at room temperature with no specifications.
Copyright: American Scientific Publishers
ture overnight to remove CTAB. The resulting solid product
(MCM-41@Fe3O4ꢃ was collected and washed with plenty
of water. The product was dried under vacuum at 60 ꢁC.
MCM-41@Fe3O4 was finally linked with silane cou-
pling reagent BPTS. To a solution of 150 mL dry
toluene was added 1 g MCM-41@Fe3O4 and 0.5 g BPTS,
then heated the suspension to reflux under Ar protec-
tion overnight. The resulting solid sample (BPTS-MCM-
41@Fe3O4ꢃ was centrifuged and washed with 200 mL
benzene and then 200 mL ꢁethanol. The solid product was
dried under vacuum at 60 C overnight.
2.2. Synthesis of Dafo-Ph-NH2
2.4. Construction of Dafo-MCM-41@Fe3O4
N1-(5H-cyclopenta[1,2-b:5,4-bꢀ]dipyridin-5-ylidene)benzene-
1,4-diamine (denoted as Dafo-Ph-NH2ꢃ was prepared
following a two-step procedure described as follows.
Firstly, 5H-cyclopenta[1,2-b:5,4-bꢀ]dipyridin-5-one (Dafo)
was prepared with 1,10-phenanthroline as starting reagent
following a literature procedure.11 Then, Dafo (10 mmol),
benzene-1,4-diamine (12 mmol), p-toluene sulfonic acid
(1 mmol) and toluene (150 mL) were mixed together
and heated to reflux for 8 hours under Ar protection.
Crude production was purified by recrystallization from
ethanol/toluene to give Dafo-Ph-NH2 as dark red powder.
1H NMR (CDCl3ꢃ: d 8.77 (s, 1H), 8.64 (s, 1H), 8.25
(s, 1H), 7.37 (s, 2H), 7.03–6.98 (m, 3H), 6.81–6.79
(m, 2H), 5.03(s, 2H). MS m/z: [m+1]+ calc. for C17H12N4,
272.1; found, 273.1.
The drug carrier: site-specific superparamagnetic compos-
ite Dafo-MCM-41@Fe3O4 was constructed as following
procedures. To a solution of 120 mL dry toluene was added
1.5 g anhydrous potassium carbonate, 0.3 g Dafo-Ph-NH2
and 0.6 g BPTS-MCM-41@Fe3O4, then raised the tem-
perature to reflux under stirring for 3 days. After cooled
to room temperature, the solid product was centrifuged,
collected and washed with distilled water to remove potas-
sium carbonate, then dried in vacuum at 60 ꢁC and
obtained as Dafo-functionalized supporting matrix.
2.5. In Vitro Cytotoxicity of the Dafo-MCM-41@Fe3O4
The in vitro cytotoxicity of the Dafo-MCM-41@Fe3O4
was determined by MTT assays, and the L929 fibroblast
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Synthesis of Light-Controlled Superparamagnetic Core–Shell Structured Nanocomposite for Drug Delivery
Chen et al.
cell line was used here. L929 fibroblast cell in 200 ꢄL
media per well were plated in a 96-well plate for 24 h
to allow the cells to attach and then exposed to differ-
ent concentrations of the Dafo-MCM-41@Fe3O4 (1.5625,
3.125, 6.25, 12.5, 25.0, 50.0 ꢄg mL−1ꢃ for 24 h in 5%
CO2 at 37 ꢁC. After that, the medium containing the
Dafo-MCM-41@Fe3O4 was removed and MTT solution
(20 ꢄL diluted in a culture medium to a final concentration
of 5 mg/mL) was added. Incubated again in the incuba-
tor for another 4 h, replace the solvent in the wells by
100 ꢄL DMSO, and the absorbance was monitored with
a microplate reader at a wavelength of 595 nm. All tests
were performed in triplicate. The cell viability was calcu-
lated using the following equation:
MCM-41 tunnels and change the tunnels’ diameter, thus
can release drug molecules when the tunnels changing
size. It is contemplated this core–shell structured compos-
ite is able to release the drug molecules under light stim-
ulated and to achieve a complete and efficient site-specific
delivery.
3.2. Morphology and Magnetic Feature of
Dafo-MCM-41@Fe3O4
Morphology of our prepared samples were analyzed by
their SEM images shown in Figure 1. The Fe3O4 par-
ticles have an uneven surface and poor dispersal with
mean diameter of about 125 nm. Aggregation can be
explained by their magnetic properties. The surface of
nanoparticle are full of small hunches and humps. How-
ever, after being coated with amorphous SiO2, the nanopar-
ticles’ surface became smooth, and the diameter increased
to about 155 nm. On the other hand, a better dispersion
can be seen on SiO2@Fe3O4 which means that the SiO2
layer can significantly reduce the attraction between those
magnetic particles. With this improved sample surface as
well as dispersal, MCM-41 growth on SiO2@Fe3O4 has
been readily performed. As what we expected, MCM-41
growth on the SiO2@Fe3O4 increased the diameter to
about 280 nm, with nearly mono-dispersal, as shown
in Figure 1. After BPTS coupling, the mean diameter
of BPTS-MCM-41@Fe3O4 shows no increase, suggest-
Cell viability (%) = ꢅAꢆtest/ꢅAꢆcontrol ×100%
2.6. Vitamin B12 Loading and Release In Vitro
200 mg of Dafo-MCM-41@Fe3O4 was suspended in
20 mL ethanol solution of vitamin B12 with a concen-
tration of 40 mg/mL at room temperature under stirring
for two overnight under 510 nm radiation to achieve
drug loading equilibrium. After Dafo-MCM-41@Fe3O4
was connected with the drug (denoted as B12-Dafo-MCM-
41@Fe3O4ꢃ, the composite was collected by centrifuga-
ꢁ
tion, washed gently by ethanol, and dried at 60 C under
vacuum overnight. The amount of vitamin B12 loaded
was determined as 0.12 mmol/g (against unloaded Dafo-
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ing that BPTS is connected into MCM-41 tunnels rather
MCM-41@Fe3O4 by concentrationIPd:if3fe7r.e9n.c4e0.b3e6foOren:anTdhu, 30 Mar 2017 12:27:04
than sample surface. After Dafo-Ph-NH2 connected, mor-
Copyright: American Scientific Publishers
after Dafo-MCM-41@Fe3O4 loading with UV-vis absorp-
phology and diameter of Dafo-MCM-41@Fe3O4 are close
to BPTS-MCM-41@Fe3O4. This core–shell structure is
further confirmed by transmission electron microscope
(TEM) of Dafo-MCM-41@Fe3O4 shown in Figure 1.
Upon the above facts, it can be concluded that the Dafo-
MCM-41@Fe3O4 has been constructed, with its core width
of 125 nm and MCM-41 shell width of 70 nm.
tion spectrophotometry). 100 mg of the obtained dry sam-
ples was compressed into disk for drug release. After drug
was loaded, the B12-loaded Dafo-MCM-41@Fe3O4 drug
disks were put into 20 mLꢁ simulated body fluid (SBF,
pH = 7ꢂ4) maintained at 37 C and stirred gently. At pre-
determined time intervals, 0.5 mL of the sample was with-
drawn and immediately replaced with the same amount of
SBF buffer to keep the volume constant. The withdrawn
solution fractions were monitored by UV-vis spectropho-
tometer at a wavelength of 360 nm.
In this research, the Fe3O4 core is designed for
site-specific drug delivery purpose, therefore it should
be magnetic guiding. The Magnetic feature of Fe3O4,
SiO2@Fe3O4 and Dafo-MCM-41-@Fe3O4 can be seen in
Figure 2. All those particles show superamagnetic behavior
there is no hysteresis. The saturation magnetization value
of Fe3O4 is 82 emu/g. According to the literature, iron
oxide particles larger than 30 nm should not have supera-
magnetic behavior.14 It was, however, not work in our case.
In Fe3O4 tiny bumps and humps bearing the surface, we
assume that all of these Fe3O4 particles are actually made
up of tiny subatomic smaller than 30 nm. After coated
by SiO2, the saturation values declined to 75 emu/g. The
magnetization values declined to 35 emu/g after the par-
ticle was further coated with MCM-41 and ligand. These
decreased values compared to saturation value of Fe3O4
nanoparticles can be explained by their decreased Fe3O4
weight ratios.
3. RESULTS AND DISCUSSION
3.1. Design Strategy of Dafo-MCM-41@Fe3O4
Scheme 1 illustrates the construction procedures of the
site specific complex Dafo-MCM-41@Fe3O4 and the drug
loading mechanism. A typical core–shell structure is
observed for Dafo-MCM-41@Fe3O4, where Fe3O4 acts as
inner core while MCM-41 acts as outer shell. The Fe3O4
core is clearly chosen for purpose of site-specific mag-
netic guiding. Its outer shell consisted of mesoporous sil-
ica molecular sieve MCM-41 which offered highly ordered
hexagonal tunnels for drug molecules.12ꢀ13 The thin amor-
phous SiO2 crust between Fe3O4 core and MCM-41
shell was built to decrease magnetic aggregation between
Fe3O4 particles and thus facilitates MCM-41 growth. The
end of ligand can flip over under light irrigation in the
Owing to its hydrophilic surface and supermagnetic
nature, Dafo-MCM-41@Fe3O4 can be easily dispersed in
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Chen et al.
Synthesis of Light-Controlled Superparamagnetic Core–Shell Structured Nanocomposite for Drug Delivery
Delivered by Ingenta to: Rice University
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Scheme 1. Synthetic procedure and the drug releasing mechanism on the site-specific composite Dafo-MCM-41@Fe3 O4.
water, forming a stable suspension. And in the magnet
field, can be readily aggregated to a specific site which
verified our purpose of designing on this compound:site-
specific guiding. The above properties can be seen in the
Figure 3.
3.4. XRD Analysis
To understand the internal structure of our nanoparti-
cles, XRD analysis was carried forward on Dafo-MCM-
41@Fe3O4 and Fe3O4 particles. Figure 5 shows the wide
angle XRD (WAXRD) patterns of the above compos-
ites. WAXRD pattern of Dafo-MCM-41@Fe3O4 particle
is close to Fe3O4 particles, which means that the mag-
netic core in Dafo-MCM-41@Fe3O4 has been well pre-
served after silica coating and drug loading procedures.
There are six detectable diffraction peaks in each curve,
marked as (220), (311), (400), (422), (551), (440), which
is consistent with literature reports.9ꢀ10ꢀ12ꢀ13 Their dif-
ferent diffraction intensity values can be explained by
the silica shell on Dafo-MCM-41@Fe3O4 surface which
weakens sample regularity. Small-angle XRD (SAXRD)
patterns of Dafo-MCM-41@Fe3O4, and MCM-41@Fe3O4
are shown in Figure 6. A strong Bragg refection peak
indexed as (200) and two weak peaks indexed as (1 0 0)
and (1 1 0) can be observed from both samples, suggest-
ing that there are mesostructure on their surface.9ꢀ10 The
intensity difference between two curves can be explained
by the ligand modification and drug loaded on it which
partially compromised these highly ordered structure. We
hereby tentatively confirmed that MCM-41 molecular
3.3. In Vitro Cytotoxicity of the
Dafo-MCM-41@Fe3O4 Composites
Since our Dafo-MCM-41@Fe3O4 nanoparticle was
designed to act as a drug carrier, the biocompatibility of
the composites must be studied. Therefore an MTT assay
was performed on these Dafo-MCM-41@Fe3O4 nanopar-
ticle. This method is based on the formation of dark red
formazan by the live cells after their exposure to MTT
(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bro-
mide). Cell viability is directly proportional to the amount
of formazan produced monitored by the absorbance at
595 nm. The concentration of our tested particle was pre-
pared from (1.5625–50 ꢄg/mL). Figure 4 shows the cell
viability of L929 fibroblast cell incubated with the com-
posites. As shown on Figure 4, no significant cytotoxicity
is observed in the Dafo-MCM-41@Fe3O4 composite in our
experiment. And we prudentially believe it is biocompati-
ble for drug delivery.
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Synthesis of Light-Controlled Superparamagnetic Core–Shell Structured Nanocomposite for Drug Delivery
Chen et al.
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Figure 1. SEM images of Fe3O4 particles (a), SiO2@Fe3O4 (b), MCM-41@Fe3O4 (c), BPTS-MCM-41@Fe3O4 (d) Dafo-MCM-41@Fe3 O4 (e), along
with the TEM of Dafo-MCM-41@Fe3 O4 (f).
sieve has been constructed as the outer shell of Fe3O4
core.
respectively, which are close to literature values.17ꢀ18
After ligand growing procedure, above value of Dafo-
MCM-41@Fe3O4 decrease to 468 m2 ·g−1, 0.31 cm3 ·g−1
and 2.64 nm. Drug loading procedure further decreases
3.5. N2 Adsorption/Desorption
above value of B12-Dafo-MCM-41@Fe3O4 to 394 m2 ·g−1
,
As we mentioned above, our purpose of synthesizing
this composite is to meet the requirement of holding the
drug molecules. Therefore the ligand modified MCM-41
shell was analyzed by N2 adsorption/desorption measure-
ment. Figure 7 shows adsorption/desorption isotherms of
Dafo-MCM-41@Fe3O4, MCM-41@Fe3O4 and B12-Dafo-
MCM-41@Fe3O4. Despite of their different intensity val-
ues, these isotherms are all type-IV ones and similar to
each other, suggesting that regular hexangular tunnels have
been successfully constructed on Fe3O4 core and well pre-
served after silica coating/probe loading procedures.15ꢀ16
For MCM-41@Fe3O4, surface area, pore volume and pore
diameter are 678.2 m2 ·g−1, 0.462 cm3 ·g−1 and 2.82 nm,
0.28 cm3 · g−1 and 2.33 nm. All these changes in
the parameters confirmed the introduction of the drug
molecules into the pores of the composites.
3.6. Determination of Drug Loading
FT-IR spectrum are demonstrated to understand the change
of the functionalized process and the interaction between
the drug and composites. From Figure 8, all three com-
posites shows strong peaks at around 3430 cm−1 and
1080 cm−1. The vibration of C–O and the association
absorption of –OH account for these two peaks. MCM-
41@Fe3O4 IR spectrum is a simple one with several
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Chen et al.
Synthesis of Light-Controlled Superparamagnetic Core–Shell Structured Nanocomposite for Drug Delivery
Figure 5. WAXRD patterns of Dafo-MCM-41@Fe3 O4 and Fe3O4
particles.
Figure 2. Magnetic feature of Fe3O4 and SiO2@Fe3O4 particles and
Dafo-MCM-41@Fe3 O4.
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Figure 3. Photos of Dafo-MCM-41@Fe3 O4 in ethanol solution in the
absence of magnetic field and presence of magnetic field.
Figure 6. SAXRD of Dafo-MCM-41@Fe3 O4, and MCM-41@Fe3 O4.
characteristic bands peaking at 458 cm−1, 604 cm−1
,
802 cm−1 and 1644 cm−1, respectively. These bands are
attributed to plane blending and stretching of Si–O–Si
framework, indicating the presence of silica coating
shell. These bands are well preserved in Dafo-MCM-
41@Fe3O4 and B12-Dafo-MCM-41@Fe3O4 IR spectrum.
When Dafo is connected to the MCM-41 shell, new
peaks of 2960 cm−1, 1680 cm−1 and 1508 cm−1 can
be seen on the spectrum, which can be assigned to
vibration of C N group and the vibration of –NH
group.11 In the IR of B12-MCM-41@Fe3O4, the ratio of
Figure 4. Cell viability of L929 fibroblast cells incubated with Dafo-
Figure 7. N2 adsorption/desorption isotherms of B12-Dafo-MCM-
MCM-41@Fe3 O4.
41@Fe3O4, Dafo-MCM-41@Fe3 O4 and MCM-41@Fe3O4.
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Synthesis of Light-Controlled Superparamagnetic Core–Shell Structured Nanocomposite for Drug Delivery
Chen et al.
Figure 10. Absorbance in visible spectrum of Dafo (2 mmol/mL in
ethanol).
Figure 8. IR spectra of MCM-41@Fe3O4, Dafo-MCM-41@Fe3 O4, and
B12-Dafo-MCM-41@Fe3 O4.
3.7. Determination of Wavelength
The light controlled release property of the Dafo-MCM-
41@Fe3O4 is cause by the flipping of C N bond, there-
fore the wavelength of exciting light should be determined.
According the literature,19 N=N bond has a maximum
absorbance at 450 nm in visible spectrum, so we tested the
absorbance of Dafo at the range from 400 to 650 nm. As
shown in the Figure 10, there is a broad peak in 510 nm
and can be assigned to ꢇ–ꢇ∗ absorption of C N bond.
As a result, in our experiment, 510 nm LED laser was used
as stimulating light to load and release drug molecules.
1680 cm−1:1508 cm−1 is almost two times higher than in
the Dafo-MCM-41@Fe3O4. The characteristic peak of B12
has strengthened the absorbance in this position suggesting
that the drug has been successfully loaded into MCM-41
tunnels.
Thermogravimetric degradation (TGA) is then applied
to confirm drug loading in B12-Dafo-MCM-41@Fe3O4, as
shown in Figure 9. For comparison purposes, Dafo-MCM-
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41@Fe3O4 was first test for TGA, there are two major
IP: 37.9.40.36 On: Thu, 30 Mar 2017 12:27:04
weight loss regions on its TGA curve. Started from 250 ꢁC
Copyright: American Sc3i.e8n. tDifircuPguRbelilsehaesers
the organic ligand begins to decompose therefore we got
the first weight lost. Then at around 480ꢁ the framework
left in Dafo-MCM-41@Fe3O4 starts to degrade which
results in the second weight lost. In the case of B12-Dafo-
MCM-41@Fe3O4, since it is drug loaded. It takes longer
to lost weight before the curve reaches the stable stage at
around 550ꢁ. In the final stage, B12-MCM-41@Fe3O4 lost
16% more weight than Dafo-MCM-41@Fe3O4, which is
close to 0.12 mmol/g.
Figure 11 displays the release behavior of vitamin B12
from the magnetic drug nanoparticle carrier in simulated
body fluids within 60 h. Without light stimulated, drug
release starts from 4% in the first half hour and bursts to
11% in 5 hours then slowly increases to 25% in 60 hours.
With 510 nm light present, the drug release speed becomes
significantly higher. Starts from 10% release rate in the
first half hour and bursts to 38% in 10 hours then reaches
59% in the final, which is two and a half times higher
than when light off. Therefore, the Dafo-MCM-41@Fe3O4
shows light controlled release property. Our nanoparticles
Figure 9. TGA of Dafo-MCM-41@Fe3 O4 and B12-Dafo-MCM-
Figure 11. Cumulative release of B12 from Dafo-MCM-41@Fe3 O4
41@Fe3O4.
with light on and light off.
4530
J. Nanosci. Nanotechnol. 17, 4524–4531, 2017

Chen et al.
Synthesis of Light-Controlled Superparamagnetic Core–Shell Structured Nanocomposite for Drug Delivery
can release drug molecules on target tissue under light
stimulating.
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4. CONCLUSION
In conclusion, a core–shell structured composite was mod-
ified by an organic ligand with a Dafo end, aiming at
releasing drug molecules under light stimulated. Its Fe3O4
core is responsible for site-specific guiding, its MCM-41
shell serves as supporting matrix for drug carrier. This
structure was analyzed and confirmed by SEM, TEM,
XRD, IR spectra, TGA and N2 adsorption/desorption.
Drug carrier’s cytotoxicity was studied by MTT using L929
fibroblast cell, and low cytotoxicity was revealed. Magnetic
measurements show that these composites exhibit sufficient
reactivity under external magnetic field. The Dafo-MCM-
41@Fe3O4 composite shows light controlled release behav-
iors for vitamin B12 in vitro. It has 2.5 times faster release
rate when light present than without light stimulated. We
tentatively concluded that Dafo-MCM-41@Fe3O4 can be
potential vectors for drug delivery.
Acknowledgment: The authors gratefully thank our
universities for their equipments and financial support.
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Delivered by Ingenta to: Rice University
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IP: 37.9.40.36 On: Thu, 30 Mar 2017 12:27:04
(2012).
Copyright: American Scientific Publishers
Received: 7 August 2015. Accepted: 18 January 2016.
J. Nanosci. Nanotechnol. 17, 4524–4531, 2017
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