Multistimuli-responsive hydrogel particles prepared via the self-assembly of PEG-based hyperbranched polymers

Article abstract of DOI:10.1246/cl.150064

Generally, it is very difficult to obtain multistimuli-responsive hydrogel particles. Here, we introduce a novel method for the preparation of multistimuli-responsive hydrogel particles by adding water into the poly(ethylene glycol) (PEG)-based hyperbranched polymers. The produced PEG-base polymers via reversible addition-fragmentation chain transfer (RAFT) polymerization become temperature-sensitive and less soluble when heated above the lower critical solution temperature (LCST) after directly adding water. Subsequently, the hydrogel particles can be formed via hyperbranch-hyperbranch coupling through disulfide exchange. The resulting hydrogel particles are temperature-, photo-, and redox-responsive.

Full text of DOI:10.1246/cl.150064

Received: January 23, 2015 | Accepted: February 11, 2015 | Web Released: March 7, 2015
CL-150064
Multistimuli-responsive Hydrogel Particles Prepared via the Self-assembly
of PEG-based Hyperbranched Polymers
Qian-Bao Chen* and Ye-Zi You
CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering,
University of Science and Technology of China, Hefei 230026, P. R. China
NO2
NO2
Generally, it is very difficult to obtain multistimuli-
responsive hydrogel particles. Here, we introduce a novel
method for the preparation of multistimuli-responsive hydrogel
particles by adding water into the poly(ethylene glycol) (PEG)-
based hyperbranched polymers. The produced PEG-base
polymers via reversible addition­fragmentation chain transfer
(a) H3C
KMnO4
NaOH
CH3
HOOC
COOH
BH3 THF
NO2
O
O
O
NO2
O
Cl
HOH C
2
CH OH
O
2
TEA
(
RAFT) polymerization become temperature-sensitive and less
(
(
b)
c)
soluble when heated above the lower critical solution temper-
ature (LCST) after directly adding water. Subsequently, the
hydrogel particles can be formed via hyperbranch­hyperbranch
coupling through disulfide exchange. The resulting hydrogel
particles are temperature-, photo-, and redox-responsive.
+
+
O
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NH
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O2N
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7
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AIBN THF 60°C
HN
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hyperbranched polymer
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Stimuli-responsive macromolecules and inducing self-
assembled architectures that can exhibit reversible or irreversible
changes in physical properties and chemical structures to
external stimulus such as pH, temperature, ionic strength, light
irradiation, etc., have sparked the interest of the basic science
and biomedical domains due to the possibility of attaining
nanometer-level control in the construction and destruction of
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Self-assembly
disassembly
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Self-crosslinking
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hyperbranched polymer
nanoparticle
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nanogel/macrogel
6­10
covalent and noncovalent interactions.
irradiation release
Of the stimuli, light
11,12
was quite attractive owing to its easy
(
d)
operation, low cost, and fast responsiveness as compared to
conventional stimuli such as pH, temperature, and other
additives.
Temperature and redox are other attractive environmental
triggers. The dual-responsive behaviors of graft copolymers are
easy to obtain and exhibit thermosensitive and redox-sensitive
1
0mM DTT 5min
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properties in water.
To the best of our knowledge, the
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hr 365nm 1h
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combination of light irradiation, temperature, and redox-
triggered release has been less exploited to develop the
hyperbranched polymer, especially via the reversible addition­
fragmentation chain-transfer polymerization.
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nanogel/ macrogel
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Figure 1. The preparation outline of multistimuli-responsive
hydrogels: (a) the synthesis of photodegradable monomer,
b) the PEG-based hyperbranched polymers via RAFT polymer-
ization, (c) the formation of crosslinking nanogels, and (d) the
decomposing process under the stimulus of DTT or 365 nm
irradiation.
Herein we demonstrate a novel design strategy. Instead
of using a single junction between the two blocks,1
5­17
the
(
photolabile and redox decomposing moieties are positioned
along the main chain as the crosslinking component. With this
design, the resulting polymer will lead to a fast release once
exposed to external stimuli.
As described in Figure 1, the photodegradable monomer
characterization using 1H NMR (Supporting Information,
Figure S6) and GPC (Supporting Information, Figure S8).
In order to track the phase transitions of the above
hyperbranched polymer in the aqueous solution, the PEG-
based hyperbranched polymer solution (polymer concentration
1
,3-di(acryloxymethyl)-2-nitrobenzene (DANB) was prepared
by three steps. Reversible addition­fragmentation chain transfer
RAFT) polymerizations of 2-(2-methoxyethoxy)ethyl meth-
acrylate (MEO2MA), oligo(ethylene glycol) methyl ether meth-
acrylate (OEGMA), N,N¤-cystaminebisacrylamide (CBA), and
DANB were carried out in tetrahydrofuran (THF) at 60 °C.
By precipitating in hexane, and drying under vacuum, the
poly(ethylene glycol) (PEG)-based hyperbranched polymers
(
¹
1
is 2 mg mL ) is configured.
When temperature was elevated to 45 °C, the transmittance
of hyperbranched polymer solution fell to 50%. The plot in
Figure 2a shows that the aqueous solution of PEG-based
hyperbranched polymer has a lower critical solution temperature
(
Mn = 33.9 kDa, PDI = 1.6) was prepared and taken for further
Chem. Lett. 2015, 44, 677–679 | doi:10.1246/cl.150064
© 2015 The Chemical Society of Japan | 677

(a)
1
00
80
60
40
20
0
2
5
30
35
40
45
50
55
60
Temperature/°C
(b)
1
0000
2.8 10000
Figure 3. The schematic illustration and images of nanogels/
macrogels responsive to DTT and ultraviolet light.
G'
G"
8
000
2.6
8000
2
2
2
1
1
1
1
1
0
.4
.2
.0
.8
.6
.4
.2
.0
.8
6
000
tan
δ
6000
of the polymer. The occurrence of crosslinking at 45 °C can be
verified by rheological results. The values of storage moduli
G¤ and loss moduli G¤¤ as functions of time were shown in
Figure 2b: it is clear that the hyperbranched polymer can easily
self-crosslink at ca. 45 °C; it took two hours to completely
crosslink the polymer.
4
2
000
000
4000
2000
δ
It has been demonstrated that degradation of the hydrogels
prepared via the self-assembly of hyperbranched polymers can
be readily realized via cleavage of the photolabile and redox-
decomposing moieties. Adding a reducing reagent to dithio-
threitol (DTT) nanogel suspension, the polymer backbone
containing disulfide will decompose. The solution containing
hyperbranched polymers will be transparent when exposed to
irradiation by ultraviolet light (365 nm) for 1 h (Figure 3).
In conclusion, we synthesized PEG-based hyperbranched
polymers bearing photolabile and redox-decomposing moieties.
The nanoparticles can be formed because the disulfides inside
the nanoparticles undergo intermolecular disulfide exchange to
crosslink on adding water into the polymerization system. The
hydrogels are temperature-, photo-, and redox-responsive. Our
results provide an illustration of the molecular design for
programming of the functions of molecular assemblies.
-20
0
20 40 60 80 100 120 140 160 180
t/min
(c)
The research was supported by the financial support
from Nation Science Foundation of China (Nos. 20974103,
Figure 2. (a) Transmittance change of PEG-based hyper-
¹
1
branched polymers solution (2 mg mL ) vs. temperature,
b) evolution of tan ¤, G¤, and G¤¤ of PEG-based hyperbranched
polymers according to time at 45 °C (oscillatory frequency
2
1074121, and 21090354).
(
¹
1
Supporting Information is available electronically on J-STAGE.
½
= 10 rad s , Gap = 900 ¯m), (c) TEM images of hydrogel
¹
1
particles on a carbon film (2 mg mL ). scale bars are 400 nm.
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Chem. Lett. 2015, 44, 677–679 | doi:10.1246/cl.150064
© 2015 The Chemical Society of Japan | 679