Dual stimuli-responsive microgels based on photolabile crosslinker: Temperature sensitivity and light-induced degradation

Article abstract of DOI:10.1002/pola.27165

The synthesis and characterization of a new photocleavable crosslinker is presented here. Dual stimuli-responsive P(VCL-co-NHMA) microgels were prepared by precipitation polymerization of vinylcaprolactam (VCL) with N-hydroxymethyl acrylamide (NHMA) and the new crosslinker. The microgels had distinct temperature sensitivity as observed in the case of PVCL-based particles and their volume phase transition temperature (VPTT) shifted to higher temperature with increasing NHMA content. Photolytic degradation experiments were investigated by irradiation with UV light, which led to microgel disintegration caused by cleavage of the photolabile crosslinking points. The degradation behavior of the microgels was conducted with respect to degradation rates by means of the relative turbidity changes. Hence, the microgels could totally degrade into short linear polymers by UV light, thus representing a great potential as new light and temperature dual responsive nanoscale materials.

Full text of DOI:10.1002/pola.27165

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Dual Stimuli-Responsive Microgels Based on Photolabile Crosslinker:
Temperature Sensitivity and Light-Induced Degradation
Shanshan Bian, Jin Zheng, Wuli Yang
State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University,
No. 220 Handan Road, Shanghai 200433, People’s Republic of China
Correspondence to: W. Yang (E-mail: wlyang@fudan.edu.cn)
Received 11 January 2014; accepted 10 March 2014; published online 25 March 2014
DOI: 10.1002/pola.27165
ABSTRACT: The synthesis and characterization of a new photo-
cleavable crosslinker is presented here. Dual stimuli-responsive
P(VCL-co-NHMA) microgels were prepared by precipitation
polymerization of vinylcaprolactam (VCL) with N-hydroxy-
methyl acrylamide (NHMA) and the new crosslinker. The
microgels had distinct temperature sensitivity as observed in
the case of PVCL-based particles and their volume phase tran-
sition temperature (VPTT) shifted to higher temperature with
increasing NHMA content. Photolytic degradation experiments
were investigated by irradiation with UV light, which led to
microgel disintegration caused by cleavage of the photolabile
crosslinking points. The degradation behavior of the microgels
was conducted with respect to degradation rates by means of
the relative turbidity changes. Hence, the microgels could
totally degrade into short linear polymers by UV light, thus
representing a great potential as new light and temperature
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KEYWORDS: microgels; photochemistry; poly(vinylcaprolactam);
radical polymerization; stimuli-sensitive polymers
derivatives have attracted extensive attention in the synthetic
organic chemistry area.24 An o-nitrobenzyl ester changes into
a corresponding o-nitrosobenzaldehyde or o-nitrosobenzo-
phenone upon irradiation with UV light based on the photoi-
somerization mechanism, simultaneously releasing a free
carboxylic acid.25,26 Linkers and protecting groups based on
o-NB chemistry can usually be cleaved when exposed to
300–365 nm light, with time varying from several hours at a
low intensity to a few minutes when applying light of high
intensities.16
INTRODUCTION The research of polymer-based microgels
has gained increasing attention since the discovery of micro-
gels as a unique class of polymeric nanoscale materials.
Microgels possess more flexible and outstanding properties,
such as fluid-like transport performance, superior colloid sta-
bility, and possible control of particle size.1,2 Especially,
stimuli-responsive microgels represent complex multifunc-
tional systems, which are able to change the physicochemical
properties of the network-forming polymers upon applica-
tion of external triggers, which mainly include tempera-
ture,3,4 pH,5–8 light,9 redox,10 and so on. Microgels can be
applied in numerous fields such as sensors,11 optics, colloi-
dal crystals,12 and biomedical fields including drug delivery
systems13–15 and biotechnology.16
Even though o-NB derivatives have been investigated in poly-
mer science since 1977,27,28 it has not been realized until
very recently that studies appeared to take full advantage of
this photo responsive group in polymer and material science
applications. For example, o-NB-based crosslinkers have been
used in the crosslinking of hydrophilic poly(ethylene glycol)
chains, making hydrogels which are commonly used as scaf-
folds in tissue engineering and drug delivery.24 Turro and
coworkers reported an example of model crosslinked net-
works based on o-NB linkers in 2007.29 Recently, dual
stimuli-responsive P(HEMA-co-MAA) microgels were pre-
pared by D. Klinger and K. Landfester with o-NB-based pho-
tolabile crosslinker, and the microgels performed pH-
dependent swelling and light-induced degradation behavior,
Light presents an outstanding position among the different
stimuli as it can be applied in a very precise manner by
selecting suitable wavelength, polarization direction, and
intensity in a noncontact approach, respectively.17,18 In addi-
tion, light offers the possibility to change the polymer prop-
erties in confined spaces and time scales. The utilization of a
broad variety of chromophores, such as aniline,19 azoben-
zene,20 spiropyran,21 and o-nitrobenzyl derivatives has in
general been realized for advantages in triggering release
applications.22,23 Among those, o-nitrobenzyl (o-NB) alcohol
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SCHEME 1 Schematic representation of the preparation and the dual stimuli-responsive characters of the photodegradable PVCL-
based microgels. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
EXPERIMENTAL
which enabled the efficient loading and subsequent release
of myoglobin as a model protein.30
Materials and Chemicals
Acetovanilone (99%) and 1,2-bis(2-chloroethoxy) ethane
Temperature-sensitive microgels have gained extensive atten-
(99%) were purchased from J&K Scientific. N-Vinylcaprolac-
tam (VCL) was obtained from Fluka. NHMA was purchased
from Aladdin Internet Reagent Database. Tetramethyl ethyl-
ene diamine (TMEDA) was purchased from TCI Tokyo
tion for their potential chemical and biomedical applica-
tions.31–35 As a thermally sensitive polymer, the closely
lower critical solution temperature (LCST) of poly(N-vinyl-
caprolactam) (PVCL) to body temperature bestowed it
Chemical Industry. Potassium persulfate (KPS), sodium
widely attention for both scientific studies and technological
applications.36,37 PVCL microgel has been proved to be an
dodecyl sulfate (SDS), and sodium bicarbonate (NaHCO3)
were purchased from Shanghai Chemical Reagents Com-
excellent drug carrier because of the swelling and shrinking
of a polymeric gel network.38–40 Few studies related to tem-
pany. All chemicals were of analytical grade or better and
used without further purification except as mentioned
above.
perature and light dual stimuli microgels have been publicly
reported though Liu’s group reported a thermo- and light-
regulated formation and disintegration double hydrophilic
block copolymer micelle.41
Characterization
1H nuclear magnetic resonance (1H NMR) (500 MHz) spectra
were obtained using a Bruker spectrometer. Ultraviolet visi-
ble (UV–vis) spectra were measured using a Perkin-Elmer
Lambda 35 spectrophotometer. Hydrodynamic diameter and
light-scattering intensity of the microgels were obtained by a
Malvern Zetasizer (Nano-ZS90) at scattering angle of 90ꢀ.
Transmission electron microscopy (TEM) images were deter-
mined on a Hitachi H-600 transmission electron microscope,
and the microgels were negative stained with 1% phospho-
tungstic acid for TEM measurement. Fourier transform infra-
red (FTIR) spectra were measured on a Nicolet Nexus-6700
FTIR spectroscopy.
On the basis of these considerations, we designed and synthe-
sized a symmetrical photolabile crosslinker ((((ethane-1,2-diylbis
(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(5-methoxy-2-nitro-4,1-
phenylene))bis(ethane-1,1-diyl)bis(2-methylacrylate) (DMANB)
through a convenient route. The cleavage behavior of the new
crosslinker was investigated by means of 365-nm UV light irra-
diation. Then, the photocleavable crosslinker was used to build
up dual stimuli-responsive P(VCL-co-NHMA) microgels. The
obtained microgels could be completely disintegrated upon irra-
diation due to the light-cleavable crosslinking points. Mean-
while, the microgels were stable in physiological condition and
the volume phase transition temperature (VPTT) could be
adjusted by changing the amount of hydrophilic co-monomer
N-hydroxymethyl acrylamide (NHMA) (Scheme 1).
The average molecular weight and molecular weight distri-
bution (Mw/Mn) of the degradable polymer linear chains
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SCHEME 2 Synthesis of photolabile crosslinker DMANB.
were estimated by gel permeation chromatography (GPC)
measurements, which were carried out on a HP Angilent
series 1100 Chromatograph equipped with a G1310A pump,
a G1362A refractive index detector, and a G1315A diode-
array detector. Poly(ethylene oxide) (PEO) standard samples
were used for calibration, and the meꢀasurement condition is
0.1 M NaNO3 aqueous solution at 40 C with an elution rate
of 0.5 mL/min.
1,10-((((Ethane-1,2-diylbis(oxy))bis(ethane-2,1-
diyl))bis(oxy))bis(5-methoxy-2-nitro-4,1-
phenylene))diethanone (4)
To a solution of 3 (2.2 g, 5 mmol) in 20 mL of acetic anhy-
dride, nitric acid (2 mL) was added dropwise at 0 ꢀC. Then,
the solution was heated to room temperature and stirred for
2 h. The precipitate was obtained by filtration and washed
with methanol for three times to give compound 4 as a light
yellow solid (1.9 g, 70% yield).
Synthesis of Photolabile Crosslinker
1,10-((((Ethane-1,2-diylbis(oxy))bis(ethane-2,1-
1H NMR (CDCl3): d 5 7.70 (s, 2H), 6.73 (s, 2H), 4.27 (t, 4H),
diyl))bis(oxy))bis(3-methoxy-4,1-phenylene))diethanone (3)
To a solution of acetovanilone 1 (4.0 g, 23.8 mmol) in 50 mL
of DMF, potassium carbonate (5.5 g, 39.8 mmol) and 1,2-
bis(2-chloroethoxy) ethane 2 (1.9 g, 10.0 mmol) wereꢀadded
(Scheme 2). The reaction mixture was heated to 120 C and
kept for 12 h under nitrogen atmosphere. The resulting solu-
tion was poured into 200 mL water and extracted with 200
mL ethyl acetate. Then, the ethyl acetate layer was washed
with Na2CO3 (5%), and then brine. The ethyl acetate layer
was dried with Na2SO4, filtered, and removed under reduced
pressure. The product was recrystallized with ethyl acetate
and hexane to give compound 3 as a pale white solid (3.0 g,
67% yield).
3.94 (s, 6H), 3.92 (t, 4H), 3.74 (s, 4H), 2.48 (s, 6H).
1,10-((((Ethane-1,2-diylbis(oxy))bis(ethane-2,1-
diyl))bis(oxy))bis(5-methoxy-2-nitro-4,1-
phenylene))diethanol (5)
To a solution of 4 (536 mg, 1 mmol) in 50 mL of THF,
NaBH4 (84 mg, 2.2 mmol) was added at room temperature
and allowed to stir at the same temperature. The reaction
progress was monitored by thin-layer chromatography. After
completion of the reaction (3 h), the reaction mixture was
quenched with aqueous solution of saturated NH4Cl. THF
was evaporated under reduced pressure and the crude mix-
ture was purified by silica gel column chromatography to
give compound 5 as a yellow solid (450 mg, 83% yield).
1H NMR (CDCl3): d 5 7.56 (d, 2H), 7.54 (s, 2H), 6.93 (d, 2H),
4.26 (t, 4H), 3.95 (t, 4H), 3.93 (s, 6H), 3.78 (s, 4H), 2.58
(s, 6H).
1H NMR (CDCl3): d 5 7.61 (s, 2H), 7.28 (s, 2H), 5.53 (m, 2H), 4.23
(t, 4H), 3.95 (s, 6H), 3.91 (t, 4H), 3.75 (s, 4H), 1.53 (d, 6H).
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TABLE 1 Synthetic Details for P(VCL-co-NHMA) Microgels
PId
c
Sample
VCL (mg)
NHMA (mg)
DMANB (mg)
Dh (nm)
P(VCL-co-NHMA-1a)
P(VCL-co-NHMA-3)
198
194
190
190
190
2
10
10
10
5
531
589
712
686
862
0.02
0.05
0.10
0.06
0.06
6
P(VCL-co-NHMA-5)
P(VCL-co-NHMA-5–2.5b)
10
10
10
P(VCL-co-NHMA-5–7.5)
15
a
c
Weight ratio of NHMA in respect to sum of NHMA and VCL.
The hydrodynamic diameter (Dh) was determined in water at 25 ꢀC by
b
Weight ratio of crosslinker DMANB in respect to monomer and 5 wt %
DLS.
d
DMANB were used if not labeled specifically.
PI, polydispersity index of the particle size, PI 5 <l2>/C2.43
((((Ethane-1,2-diylbis(oxy))bis(ethane-2,1-
diyl))bis(oxy))bis(5-methoxy-2-nitro-4,1-
by DLS measurement. By monitoring the hydrodynamic
diameters of the particles as a function of NHMA content
with changing temperature from 25 to 60 C, different VPTT
of the family of P(VCL-co-NHMA) were obtained. The stabili-
zation time between each measurement was 300 s.
ꢀ
phenylene))bis(ethane-1,1-diyl)bis(2-methylacrylate)
To a solution of compound 5 (270 mg, 0.5 mmol) in 25 mL
DCM, triethylamine (500 lL) was added into the mixture at
ice bath temperature. To this, methacryloyl chloride (200 lL)
in dichloromethane (25 mL) was added dropwise and stirred
for 12 h at room temperature. The reaction mixture was
quenched with water, extracted with dichloromethane, and
the combined organic extracts were dried over Na2SO4 and
evaporated under reduced pressure. The crude product was
purified by silica gel column chromatography to give the
crosslinker DMANB as yellow oil (300 mg, 89% yield).
Photocleavable Studies of DMANB
A quartz cuvette containing a solution of the crosslinker
DMANB in DMSO (c 5 0.01% w/v) for UV–vis measurements
and in DMSO-d6 for 1H NMR was placed under a UV lamp
(k 5 365 nm, I 5 90 mW/cm2) and the measurements were
performed, respectively, after the sample being irradiated for
fixed time intervals.
1H NMR (DMSO-d6): d 5 7.67 (s, 2H), 7.02 (s, 2H), 6.52 (q,
2H), 6.18 (s, 2H), 5.62 (s, 2H), 4.23 (t, 4H), 3.95 (s, 6H), 3.91
(t, 4H), 3.74 (s, 4H), 1.95 (s, 6H), 1.66 (d, 6H).
Photodegradation of DMANB-Crosslinked Microgels in
Water
Samples of 0.125% (w/v) microgels in water were placed in
a quartz cuvette and irradiated with 365-nm UV light. Sam-
ples were prepared and turbidity measurements were con-
Preparation of DMANB-Crosslinked P(VCL-co-NHMA)
Microgels by Precipitation Polymerization
ducted by using
a
Malvern Zetasizer. After every
Crosslinked P(VCL-co-NHMA) microgels were synthesized by
measurement, the irradiated sample was retained by return-
ing the withdrawn samples to the cuvette. The turbidity was
determined by calculating the ratio of the scattering intensity
at 90ꢀ of the irradiated samples relative to the nonirradiated
sample. Particle size distributions of the irradiated particle
dispersions were obtained by DLS in water.
a
redox-initiated, aqueous precipitation polymerization
approach.42 Microgels were prepared by first mixing VCL,
NHMA, water (20.0 g, 1.1 mol), and 5 wt % of the cross-
linker DMANB dissolving in 1 mL DMSO. In the synthesis of
the family of P(VCL-co-NHMA) microgels, 1 wt % of the sum
of VCL and NHMA but different mass ratios of VCL to NHMA
(VCL/NHMA: 99/1, 97/3, 95/5) were used (Table 1). Here-
after, the mixture was added to a 50-mL glass flask contain-
ing 10.0 mg (5 wt % to monomers) SDS, 10.0 mg (5 wt %)
NaHCO3, then the contents of the vial were heated to 50 ꢀC
and kept under nitrogen atmosphere. After mechanical stir-
ring of 200 rpm for 1 h, the initiator, KPS (10.0 mg) in 1 mL
water was added to the mixture, followed by 10 lL of the
activator TMEDA. The polymerization reaction, while
shielded from light, was conducted under nitrogen condition
for 6 h. After the polymerization, the obtained microgels
were dialyzed for a week via a dialysis bag (molecular
weight cutoff 14,000) to remove the excess surfactant and
the unreacted reagents and impurities.
RESULTS AND DISCUSSION
A novel dual stimuli-responsive P(VCL-co-NHMA) microgel
was synthesized by redox-initiated precipitation polymeriza-
tion with a new photolabile crosslinker DMANB. The synthe-
sized crosslinker structure was determined by 1H NMR and
its photolabile behavior was analyzed by 1H NMR and UV–
vis measurement with the irradiation by 365-nm UV light.
The existence of VCL led to the temperature-sensitivity of
the microgels and the microgels exhibited higher VPTT with
the increasing content of the co-monomer NHMA. Light sen-
sitivity of the microgels was achieved by the utilization of
the new photolabile crosslinker. Irradiation of the microgels
by UV light resulted in the degradation of the crosslinking
points and further to the disintegration of the particle struc-
ture. This dual stimuli-responsive property was designed to
enable the thermosensitivity microgels degrade under the
Thermosensitivity Studies of Crosslinked P(VCL-co-
NHMA) Microgels
The microgels were dispersed in phosphate buffer of pH 7.4
and the thermosensitivity of the microgels was determined
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was put forward to explain the photoreaction.9 The photola-
bile crosslinker degraded into a molecule containing two
ketone moieties and two carboxylic acid groups under UV
light.
Time-dependent 1H NMR spectra and UV–vis measurements
of the crosslinker solution in DMSO were performed to
investigate the photolytic performance of the new photola-
bile crosslinker (Fig. 2). As was shown in Figure 2(a), the
peaks of b and c were assigned to the protons of double
bonds of methacrylic acid ester and the peak of d was
assigned to the proton of methine of phenethyl alcohol.
Along with the irradiation with 365-nm UV light, the peaks
of b, c, and d decreased at the same ratio, which indicated
the generation of ketone moieties, and meantime the peaks
of b0 and c0 increased, which were assigned to the protons of
opened methacrylic acid. The peaks of b, c, and d vanished
FIGURE 1 1H NMR (DMSO-d6) spectrum of crosslinker DMANB.
irradiation of 365-nm UV light, which had potential use in
the biochemistry field.
Synthesis of Crosslinker DMANB
To obtain the photodegradable microgel, we designed and
synthesized
a symmetrical photodegradable crosslinker
DMANB (Scheme 2). Here, a methoxy-nitrobenzyl ether
derivative was selected as the photodegradable part because
of its well-established chemistry and great utilization in
numerous biological applications. Also, a triethylene glycol
spacer was introduced to the nitrobenzyl unit in order to
improve its solubility in water. The key photodegradable
crosslinker DMANB was obtained in four steps as shown in
Scheme 2 which was shorter than the routes of former
crosslinkers9,30,44 and compound 3, 4, 5, DMANB have not
been reported. First, the phenolic hydroxyl group of starting
acetovanilone 1 was treated with 1,2-bis(2-chloroethoxy)
ethane 2 to form 3. Acetic anhydride was a selective solution
for the nitration because the product 4 would precipitate
from acetic anhydride to avoid the byproduct. The nitro-
acetovanillone derivative 4 was reduced by NaBH4 and then
followed by methacrylation of terminal hydroxyl groups to
yield the crosslinker DMANB.9
1H NMR spectrum of DMANB was shown in Figure 1. The
peaks of a, b, and c were assigned to the protons of metha-
crylic acid ester. The peaks of f and g were assigned to the
protons of benzene ring and the peaks of i, j, and k were
assigned to the protons of triethylene glycol spacer.
Photolysis of Crosslinker DMANB in Solution
The crosslinker consists of a central o-nitrobenzylic group,
the respective molecular attachment of the radically photola-
bile chromophore resulted in two mainly photoproducts as
shown in Figure 2(a). A radical mechanism including a rear-
rangement and bond cleavage following by the intramolecu-
lar benzylic hydrogen abstraction by a nitro oxygen group
FIGURE 2 Irradiation of the new photolabile crosslinker
DMANB in DMSO for an intensity of 90 mW/cm2 at 365-nm UV
light: time dependent (a) 1H NMR spectra; (b) UV–vis spectra.
[Color figure can be viewed in the online issue, which is avail-
able at wileyonlinelibrary.com.]
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swelling and degradation property of the microgels, 5 wt %
of crosslinker was added generally. After being dialyzed for a
week via a dialysis bag to remove the excess surfactant, the
unreacted reagents and impurities, the mean hydrodynamic
diameters of microgels were obtained by DLS measurements.
To investigate the conversion of the monomers with the new
crosslinker DMANB, P(VCL-co-NHMA-5) microgels were pre-
pared in deuterium oxide and the products at different reac-
tion time were analyzed by 1H NMR.10 Figure 3 showed the
conversion of main monomer VCL, which indicated most VCL
had been polymerized into polymers in 3 h. In spite of the
good conversion of VCL, the new crosslinker performed
slower conversion rate comparing with methylene biacryla-
mide48 and N,N-bis(acryloyl) cystamine (BAC)10 on account
of the inhibition and retardation effects of o-NB-based cross-
linker DMANB on the free radical polymerization. Size distri-
butions of P(VCL-co-NHMA) with different NHMA content
measuring by DLS were shown in Figure 4(a) which
FIGURE 3 Evolution of the conversion of VCL.
in 6 min and b0 and c0 got maximum values at the same
time, which indicated the end of the reaction.
In Figure 2(b), irradiation with 365-nm UV light resulted in
a red shift of the absorption maximum at 350 nm and the
reduction of the absorbance at 305 nm. Two new absorption
bands at 270 and 380 nm arose under irradiation as shown
in Figure 2(b). The spectra changed slowly after 240 s,
which meant the crosslinker almost photolysis totally under
365-nm UV light. These light-induced changes of the spectra
toward well-defined isosbestic points over the complete irra-
diation time scale points, which indicated a successful cleav-
age of the chromophore in sympathy with the research of
D. Klinger and K. Landfester.45
Preparation of DMANB-Crosslinked P(VCL-co-NHMA)
Microgels
DMANB-crosslinked P(VCL-co-NHMA) microgels were pre-
pared by precipitation polymerization, which is a most com-
mon technique for the preparation of thermosensitive
microgels.46 With regard to the preparation of polymeric
microgels, the precipitation polymerization technique is a
simple one-pot preparation method. In the process of precip-
itation polymerization, the growing polymer chains collapse
when they reach a critical length with the phase-separation
from the continuous medium above its LCST to form particle
nuclei.4 The sulfate groups from initiator incorporated into
polymer chains to stabilize the larger polymer colloid, which
is the result of the nuclei further aggregate. The resulting
microgel aqueous dispersion is a swelling network at room
temperature and could be stable by the formation of hydro-
gen bonds between water molecules and polymer segments.
In this work, a dual-stimuli responsive PVCL-based network
was prepared with VCL, NHMA, and the new photolabile
crosslinker DMANB by precipitation polymerization (Scheme
1 and Table 1). KPS acted as initiator, and NaHCO3 was used
as buffer to avoid the hydrolysis of VCL.47 The incorporation
of co-monomer NHMA controlled the VPTT of the copolymer
with changing the mass of NHMA. In order to compare the
FIGURE 4 (a) Size distribution of P(VCL-co-NHMA) microgels
with different NHMA content measuring by DLS at 25 ꢀC.
(b) Typical TEM image of P(VCL-co-NHMA-1). The dark ring in
the TEM image was obtained by stained phosphotungstic acid
to enhance the polymer contrast. [Color figure can be viewed in
the online issue, which is available at wileyonlinelibrary.com.]
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spectrum of P(VCL-co-NHMA-5) was attributed to the typical
bending vibration of amide from PNHMA,54 which indicated
that NHMA had been copolymerized into the microgels suc-
cessfully via the crosslinker DMANB. In the spectrum of
P(VCL-co-NHMA-5), the peak at 1718/cm was caused by the
stretching vibration of C5O belonged to crosslinker
DMANB,55 which demonstrated that the crosslinker had been
successfully introduced into the microgels.
Thermosensitivity of the Microgels
The prepared microgels were designed to exhibit
a
temperature-sensitivity behavior on the basis of VCL mono-
mer. With the aim to investigate the described behavior, the
DLS measurements were used as shown in Figure 6 under a
heating process. As expected, the DLS results showed a
decreasing hydrodynamic diameters with an increase in tem-
perature, which corresponded to a sharp volume phase tran-
sition as observed in PVCL-based crosslinked particles.56 The
hydrodynamic diameter of P(VCL-co-NHMA-1) microgels
decreased from 550 nm at 25 ꢀC to 437 nm at 55 ꢀC. By
comparing the temperature-sensitivity behavior of the three
microgels, it was noteworthy that the microgels owned
higher VPTT with the increasing NHMA content. The VPTT of
the P(VCL-co-NHMA-1) microgels was 41 ꢀC, while that of
P(VCL-co-NHMA-3) and P(VCL-co-NHMA-5) microgels shifted
to 44 and 48 ꢀC, respectively. These results indicated that
hydrophilic co-monomer NHMA was able to control a shift to
the higher temperature for VPTT of microgels.
FIGURE 5 FTIR spectra of NHMA, P(VCL-co-NHMA-5) and the
crosslinker DMANB (from up to down). [Color figure can be
viewed in the online issue, which is available at wileyonlinelibrary.
com.]
indicated that all microgels had good size distribution (PI ꢁ
0.10) and the hydrodynamic diameter increased from 531 to
712 nm with increasing the mass of NHMA in the recipe
from 1 to 5 wt % (Table 1). The microgels were more swol-
len with more hydrophilic NHMA incorporated into the poly-
mer network, leading to larger size.49 With the increasing
mass content of NHMA, the growing polymer chains became
more hydrophilic and were unable to complete efficient
chain collapse, which resulted in the decrease of the particle
nucleic number, leading to a larger size.50 When the weight
ratio of NHMA in respect to sum of monomer was fixed at 5
wt %, with the feeding amounts of DMANB crosslinker from
2.5 to 7.5 wt %, the hydrodynamic diameter of the as-
prepared microgels increased from 686 to 862 nm which
resulted that P(VCL-co-NHMA) microgels with high cross-
linker density were usually higher in the consideration of
their total size.51
Photodegradation of DMANB-Crosslinked P(VCL-co-
NHMA) Microgels
Photodegradation of the P(VCL-co-NHMA-5) microgels (c 5
0.125% w/v) was investigated by irradiating particles by
365-nm UV light. The light-induced degradation behavior
was determined by turbidity of the samples. Turbidity was
characterized as the relative scattering intensity at 90ꢀ by
DLS measurements. The degradation of cleavable
Figure 4(b) showed the TEM image of P(VCL-co-NHMA-1),
which exhibited uniform and regular spherical morphology.
The size of the microgel observed in TEM was about 300
nm. DLS measurements yielded the hydrodynamic diameters
of the swollen microgels showed an obvious increase com-
pared to the values obtained from TEM measurement. We
reckoned that the microgels could be swollen in an aqueous
solution during the DLS measurement while they collapsed
in dry state in a TEM testing.51,52
The FTIR measurement was used to confirm the structure of
P(VCL-co-NHMA) microgels. The FTIR spectra were shown in
Figure 5. The peaks appearing at 1634/cm caused by amide
I band and 1480/cm of C-N belonged to the characteristic
peaks of PVCL.16 The bands at 2930, 2856, and 1443/cm
were attributed to stretching and bending vibrations of C-H
groups. The spectrum of P(VCL-co-NHMA-5) performed
higher intensity peaks at 2930 and 2856/cm with respect to
the pure crosslinker DMANB on account of abundant -CH2
groups in PVCL.53 The peak appearing at 1541/cm in the
FIGURE 6 Effect of NHMA content on the temperature depend-
ence of the hydrodynamic diameter of the P(VCL-co-NHMA)
microgels in phosphate buffer of pH 7.4. [Color figure can be
viewed in the online issue, which is available at wileyonlineli-
brary.com.]
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FIGURE 7 Investigations on the light-induced P(VCL-co-NHMA-5) microgels degradation with 365-nm UV light: (a) The relative tur-
bidity for different light intensities at 25 ꢀC; (b) The degradation behavior of collapsed state for an intensity of 270 mW/cm2 at 60
ꢀC; (c) The size changes of the microgels at an intensity of 270 mW/cm2 at 25 ꢀC; (d) GPC measurement [the embedded photo-
graph was the comparison of undegraded microgels (left) and degraded microgels (right)]. [Color figure can be viewed in the
online issue, which is available at wileyonlinelibrary.com.]
crosslinking points led to a loosening of the network struc-
ture which resulted in the decreased turbidity, because a
more swollen gel particle was measured by a reduced con-
trast in the refractive indices between solvent and particles.9
15 min. In consideration of the temperature sensitivity of the
microgels, photodegradation behavior of the collapsed P(VCL-
co-NHMA-5) microgels (c 5 0.125% w/v) was also investi-
ꢀ
gated by irradiating particles by 365-nm UV light at 60 C. It
was interesting that it performed a faster degradation rate in
480 s at collapsed state for completely degradation at 270
mW/cm2 than 900 s at swollen state as shown in Figure 7(b).
Figure 7(a) showed the resulting turbidity curve of P(VCL-co-
NHMA-5) microgels with UV light of the wavelength of 365
nm, and all the three different intensities could lead to a coꢀm-
plete degradation of the microgels in different time at 25 C.
An intensity of 90 mW/cm2 did result in a decay of the tur-
bidity down to a constant level of zero in about 90 min. In
contrast, increasing the UV light intensity up to 180 and 270
mW/cm2 resulted in a faster degradation for microgels while
50 min for 180 mW/cm2 and 15 min for 270 mW/cm2,
respectively. In general, it is possible to control the degrada-
tion rate via changing the light intensity and irradiation time
used. After the irradiation of 365-nm UV light at the three dif-
ferent intensities for a certain time, the turbid dispersion
turned into the corresponding transparent solution as shown
in Figure 7(d). The imbedded photograph right in Figure 7(d)
was made by irradiating microgels at 270 mW/cm2 for
To better demonstrate the photodegradable property of
DMANB crosslinked P(VCL-co-NHMA) microgels, the microgels
were tested with 365-nm UV light at an intensity of 270 mW/
cm2 and the particle size and size distribution of the micro-
gels were measured by DLS at different time intervals. As
shown in Figure 7(c), the microgels had the mean size of 698
nm before degradation and swelled to 752 nm within 60 s
due to the decreased crosslinking density by the rupture of
some crosslinking points. After degradation of 660 s, only a
peak of 4 nm was observed which could demonstrate the
microgels completely degrade into short linear polymers. For
a further analysis of the molecular weight of the degraded
polymer chains under the irradiation of UV light, GPC
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14 M. Hamidi, A. Azadi, P. Rafiei, Adv. Drug Deliv. Rev. 2008,
60, 1638–1649.
measurement was used. The degraded polymer was filtered
through a 0.45-lm filter before its injection to GPC to avoid
Mw influence from other polymer chains. In Figure 7(d), the
GPC trace showed that the degraded polymer had a low
molecular weight (Mw, 1990 g/mol) and narrow molecular
weight distribution (Mw/Mn, 1.1) which indicated the cross-
linking points in the microgels were cleaved under irradiation
of UV light leading to the formation of short linear polymers.
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CONCLUSIONS
A novel photodegradable dual stimuli-responsive P(VCL-co-
NHMA) microgel was prepared by redox-initiated precipita-
tion polymerization of VCL and hydrophilic co-monomer
NHMA with a new photolabile crosslinker DMANB. The
crosslinker was synthesized in a facile route and it per-
formed a good photolabile behavior. The obtained microgels
presented uniform spherical shape and narrow size distribu-
tion (PI ꢁ 0.1). These microgels exhibited higher VPTT with
increasing NHMA content. UV light irradiation caused cleav-
age of the DMANB crosslinking points leading to microgel
disintegration. The microgels could totally degrade into short
linear polymers by UV light and increasing light intensity
resulted in a faster degradation. By changing light properties,
we could control the degradation rate of microgels, which
may indicate the potential application in some fields.
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ACKNOWLEDGMENTS
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We are grateful for the support of the National Science Founda-
tion of China (Grant No. 51273047) and the “Shu Guang” project
(12SG07) supported by Shanghai Municipal Education Commis-
sion and Shanghai Education Development Foundation. We thank
Yanlei Yu (Fudan University) for helping with the UV lamp.
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