One-step synthesis of pegylated cationic nanogels of poly(N,N′-dimethylaminoethyl methacrylate) in aqueous solution via self-stabilizing micelles using an amphiphilic macroRAFT agent

Article abstract of DOI:10.1016/j.polymer.2010.03.036

Cationic nanogels of Pegylated poly(N,N′-Dimethylaminoethyl methacrylate) (PEG-PDAEMA) have been synthesized in aqueous solution by a one-step surfactant-free reversible addition-fragmentation transfer (RAFT) process. A Pegylated amphiphilic macroRAFT agent (mPEG₅₅₀-TTC) with a hydrophobic dodecyl chain was utilized to stabilize the micelles and control the polymerization and crosslinking of DMAEMA in aqueous solution. ¹H NMR, GPC, Elemental analysis, Dynamic light scattering (DLS), Zeta potential and Atomic force microscopy (AFM) measurements confirmed the formation of the cationic nanogels in size of about 20?nm with a narrow distribution. It also revealed that the concentration of monomer and the kinds of crosslinker are the key factors to control the formation of nanogel. This cationic nanogel has potential application in gene delivery.

Full text of DOI:10.1016/j.polymer.2010.03.036

Polymer 51 (2010) 2161e2167
Contents lists available at ScienceDirect
Polymer
journal homepage: www.elsevier.com/locate/polymer
One-step synthesis of pegylated cationic nanogels of poly(N,N0-dimethyl-
aminoethyl methacrylate) in aqueous solution via self-stabilizing micelles using
an amphiphilic macroRAFT agent
*
Lifeng Yan , Wei Tao
Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemical Physics, University of Science and Technology of China, Hefei 230026, PR China
a r t i c l e i n f o
a b s t r a c t
Cationic nanogels of Pegylated poly(N,N0-Dimethylaminoethyl methacrylate) (PEG-PDAEMA) have been
synthesized in aqueous solution by a one-step surfactant-free reversible addition-fragmentation transfer
(RAFT) process. A Pegylated amphiphilic macroRAFT agent (mPEG550-TTC) with a hydrophobic dodecyl
chain was utilized to stabilize the micelles and control the polymerization and crosslinking of DMAEMA
in aqueous solution. 1H NMR, GPC, Elemental analysis, Dynamic light scattering (DLS), Zeta potential and
Atomic force microscopy (AFM) measurements confirmed the formation of the cationic nanogels in size
of about 20 nm with a narrow distribution. It also revealed that the concentration of monomer and the
kinds of crosslinker are the key factors to control the formation of nanogel. This cationic nanogel has
potential application in gene delivery.
Article history:
Received 22 October 2009
Received in revised form
16 March 2010
Accepted 19 March 2010
Available online 27 March 2010
Keywords:
Nanogel
Cationic
RAFT
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
polymerizations such as atom transfer radical polymerization
(ATRP) [11], nitroxide-mediated polymerization (NMP) [12] and
Nanogel is a kind of crosslinked polymer in size of nanometers
with attracting properties [1e3], which has potential application in
biomaterials, such as the delivery system for protein, polypeptide,
RNA and DNA [4e7]. Pegylated of nano-carriers for drug delivery
have attracted special attention for PEG chain can improve the
biocompatible and stability of the carriers in blood. There are
several methods to induce the PEG chains into polymers. Kim et al.
reported the synthesis of copolymer nanogel of a Pegylated poly-
(N-isopropyl acrylamide) (PNIPAM) by a PEG-macroinitiator in
a mixture solvent of water/tetrahydrogenfuran or in pure water [8].
Leobandung et al. reported the synthesis of the Pegylated PNIPAM
nanospheres by copolymerization of PEG macro-monomer with
NIPAM, and the product showed both thermo-sensitivity and high
insulin loading ability [9]. Deng et al. prepared a poly(acrylic acid)-
g-PEG nanogel with pH-responsive properties, which made the
drug of protein stable in stomach environment and has an efficient
releasing of drug in high pH condition [10].
reversible addition-fragmentation transfer (RAFT) polymerization
[13] have also been utilized for the synthesis of nanogels. Among
them, a surfactant-free method has been paid much attention and
developed by using an amphiphilic macroinitiator as surfactant, and
the self-assembly of which results in the formation of micelles and
makes itstable during polymerization[14]. RiegerandCharleuxet al.
recently prepared the Pegylated thermally responsive block copoly-
mer micelles and nanogels of poly(N,N-diethylacrylamide) and poly
(N,N-dimethylacrylamide) via an in situ RAFT aqueous dispersion
polymerization [15]. However, they found that it always results in the
formation of macroscopic gel when an amphiphilic PEO2000-TTC
macroRAFT agent was utilized to control the polymerization of
monomer in the presence of crosslinker MBA (4.6 mol%), and they
believed that the length of hydrophilic PEO2000 is not long enough to
stabilize the micelles during polymerization [15]. So they developed
a two-step strategybased onsequential additionof themonomerand
MBA, and prepared PDEAAm nanogel in size of about 500e800 nm
[15]. Another method they developed is increasing the hydrophilicity
of the macroRAFT. They utilizedmPEO-b-PDMAAmmacroRAFTagent
instead of PEO-TTC in a one-step reaction, and successfully prepared
the nanogel of PDEAAm in size of tens of nanometer [15]. However,
we think it is still possible to prepare nanogels in one-step process by
the PEG-TTC macroRAFT agent using different monomer, crosslinker,
controlling the concentrations of monomer, or shorting the length of
Generally, the synthesis of nanogel was carried out in diluted
monomer solution or in heterogeneous media, such as micro- or
mini-emulsion under the assistant of surfactant. Living radical
* Corresponding author. Tel.: þ86 551 3606853; fax: þ86 551 3602969.
E-mail address: lfyan@ustc.edu.cn (L. Yan).
0032-3861/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.polymer.2010.03.036

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L. Yan, W. Tao / Polymer 51 (2010) 2161e2167
the PEG chain. In addition, the synthesisofPegylatedcationic nanogel
is still an attractive topic for potential application in gene delivery
[16,17].
Poly(N,N0-dimethylaminoethyl methacrylate), PDMAEMA, as
one kind of cationic polymer, has both thermo- and pH-responsive
behavior, which make it an attracting polymer for gene delivery
[18]. There are many reports on the synthesis of PDMAEMA and
various copolymers of it for gene delivery [19e21]. However, there
is still seldom study on the synthesis of the nanogels of PDMAEMA,
especially Pegylated PDAEMA nanogel [22].
Here, a Pegylated cationic PDMAEMA nanogel was tried to be
prepared by a RAFT process in one-step in the absence of surfactant,
and the polymerization and crosslinking of DMAEMA monomer
were carried out in the micelles which were formed and stabilized
by an amphiphilic Pegylated macroRAFT agent, mPEG550-TTC.
Scheme 2. The synthesis sketch map of the Pegylated PDMAEMA nanogel controlled
by the amphiphilic mPEG550-TTC macroRAFT agent.
2. Experimental section
2.1. Materials
aqueous solution was added slowly below 10 ꢀC. After stirring for
another 15 min, a carbon disulfide solution in acetone was added
dropwise (CS2: 3.05 g, 40 mmol; acetone: 4.03 g, 69 mmol). Next the
system was stirred for another 15 min, and then 7.13 g chloroform
(60 mmol) and 16 g of 50 wt% sodium hydroxide (200 mmol) were
added below 10 ꢀC. The ice bath was removed 30 min later, and the
reaction was carried out for 12 h, and then 60 mL of distilled water
and 10 mL of hydrochloric acid (13.6 M) were added. After 30 min,
the system was distilled under reduced press to remove the volatile
solvents and there appeared some yellow precipitation, and which
was collected by filtration. Then the precipitation was dissolved into
200 mL isopropanol under strong stirring, and the undissolved
residuewas removedbyfiltration. After that, the filtratewasdistilled
under reduced press to remove isopropanol, and the residue was
recrystallized in hexane and was dried in vacuum for 24 h. At the
Acetone, Carbon disulfide, Isopropanol, Tetrabutyl ammonium
bromide, Sodium hydroxide, Chloroform, Hexane, and Diethyl
ether were purchased from Sinopharm Chemical Reagent (AR). N,
N0-Dicyclohexylcarbodiimide (DCC, Shanghai Medpep, 99%),
Dodecanethiol (Acros, 99%), mPEG550 (Alfa Aesar, 98%), N,N0-
dimethylamino pyridine (DMAP, Acros, 98%), 4,40-Azobis (cyano-
valeric acid (V501, Alfa Asear, 98%), and N,N0-Dimethylaminoethyl
methacrylate (DMAEMA, Alfa Asear, 97%) were used directly as
received. Azobisisobutyronitrile (AIBN, Shanghai First Reagent Co,
95%)
was
recrystallized
from
methanol.
N,N0-methyl-
enebisacrylamide (MBA, Sinopharm Chemical Reagent, 96%) was
recrystallized twice from methanol before use. Ultra-pure water
(18.2 MU) was produced by a Millipore System (Millipore Q, USA).
end, 9.1 g TTCA RAFTagent was obtained.1H NMR(CDCl3,
(t, 3H, CH2CH3 of the C12H25 chain moiety), 1.23e1.47(m, 18H,
eCH2(CH2)9CH3), 1.67e1.75 (m, 8H, eC(CH3)2eSC(S)
d ppm), 0.9
2.2. Synthesis of S-1-dodecyl-S0-(
trithiocarbonate (TTCA) RAFT agent
a,a a
0-dimethyl-
00-acetic acid)
SeCH2CH2(CH2)9CH3), 3.25(t, 2H, eSC(S)SeCH2CH2e).
The TTCA RAFT agent was synthesized by a method reported in
ref. [23]. In brief, 8.08 g dodecanethiol (40 mmol), 20 mL acetone,
and 0.52 g tetrabutyl ammonium bromide (1.6 mmol) were added
into a 100 mL flask, and it was bubbled with nitrogen gas for 30 min
at 10 ꢀC. After that, 3.35 g 50 wt% sodium hydroxide (42 mmol)
2.3. Synthesis of the amphiphilic mPEG550-TTC macroRAFT agent
mPEG550-TTC macroRAFT agent 6 was synthesized by the reac-
tion of mPEG550 and the TTCA (Scheme 1). Typically, 0.51 g mPEG550
Scheme 1. Synthesis process of the amphiphilic mPEG550-TTC macroRAFT agent.

L. Yan, W. Tao / Polymer 51 (2010) 2161e2167
2163
Fig. 1. 1H NMR spectra of TTCA and the amphiphilic mPEG550-TTC macroRAFT agent in CDCl3.
(0.93 mmol) was dissolved into 150 mL toluene, and it was refluxed
for 24 h. Then toluene was removed by distilling, and 50 mL of
anhydride dichloromethane was added to dissolve PEG550. After
that, 0.728 g TTCA (2 mmol), 0.013 g DMAP (0.106 mmol) and
0.433 g DCC (2.1 mmol) were added into the flask, and the reaction
was carried out 24 h at room temperature. Next dichloromethane
was removed by distilling, and the product was purified by column
chromatography using the mixture of dichloromethane, hexane
and diethyl ether as eluent (2:1:1).
solution was bubbled by nitrogen gas for 60 min. Then the reaction
was carried out for 48 h at 65 ꢀC, and the reaction was quenched by
decreasing the temperature to 0 ꢀC in an ice-bath. The product was
dialyzed for two days with dialysis bag, and was freeze dried.
2.5. Polymerization and crosslinking of DMAEMA controlled
by the amphiphilic mPEG550-TTC macroRAFT agent
The mPEG550-TTC macroRAFT agent, initiator AIBN or V501,
DMAEMA and crosslinker MBA with various ratios were added into
deionized water, and the solution was bubbled by nitrogen gas for
60 min. Then the reaction was carried out for 48 h at 65 ꢀC, and the
reaction was quenched by decreasing the temperature to 0 ꢀC in an
ice-bath. The product was dialyzed for two days with dialysis bag
(Mw:8000e10 000), and was freeze dried. The process was
described in Scheme 2. The mPEG550-TTC macroRAFT is amphi-
philic and it produced micelle at suitable concentration in water.
The self-assemble of the hydrophobic dodecyl groups forms the
core while the PEG segment works as the shell, and the trithio-
carbonate segment is at the interface. There formed a colloid when
mixing the RAFT agent, monomer, crosslinker and initiator in water
at 65 ꢀC, and the polymerization of DMAEMA monomer was carried
2.4. Synthesis of mPEG550-PDMAEMA linear diblock copolymer
by mPEG550-TTC macroRAFT agent in water
The linear diblock copolymer of mPEG550-PDMAEMA was
synthesized by aqueous dispersion polymerization of DMAEMA in
the presence of the mPEG550-TTC macroRAFT agent. In a typical
experiment, 6.4 mmol of DMAEMA, 0.24 mmol of mPEG550-TTC and
0.27 mmol of V501 were dissolved in 25 ml of water, and the
Table 1
Reaction condition for the three sample preparation.
Sample 1
Sample 2
Sample 3
DMAEMA
mPEG550-TTC
Initiator
3 mmol
0.14 mmol
6 mmol
0.28 mmol
6.4 mmol
0.24 mmol
AIBN: 0.015 mmol AIBN: 0.042 mmol V501: 0.27 mmol
Crosslinker MBA 0.13 mmol
0.2 mmol
20 mL
0.26 mmol
25 mL
Water
4 mL
24
26
28
30
32
Monomer
concentration
0.75 M
0.3 M
0.26 M
Retention Time (min)
Product
Macroscopic gel
Nanogel
Nanogel
Fig. 2. GPC trace of mPEG550-PDMAEMA linear copolymer.

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L. Yan, W. Tao / Polymer 51 (2010) 2161e2167
(polymer chain or colloid particle) in dilute solution or dispersion
by D ¼ (<
>/q2)C/0,q/0 and further to hydrodynamic radius (Rh)
, kB,
G
from the StokeseEinstein equation: Rh ¼ kBT/(6phD), where
h
and T are the solvent viscosity, the Boltzmann constant, and the
absolute temperature, respectively. Hydrodynamic radius distri-
bution f(Rh) was calculated from the Laplace inversion of a corre-
sponding measured
dynamic LLS measurements were conducted at a small scattering
angle (
) of 15ꢀ. AFM images were captured in the tapping mode by
G
(2)(t,q) using the CONTIN program. All
q
a NanoScope IIIa MultiMode SPM (Digital Instruments Inc., Santa
Barbara, CA) at room temperature. Silicon tip (model TESP,
Nanoprobes, Digital Instruments) with cantilever length of 125 mm
and resonant frequency of about 300 kHz was used. The scan rates
were in between 0.5 and 1.0 Hz. Height image with 512 ꢁ 512
points were recorded and analyzed by using the AFM software,
WSxM 4.0 (Nanotec Electronic S. L.) and Photoshop 5.0. Zeta
potential of the nanogel was measured by laser doppler velocim-
etry (LDV) at 25 ꢀC using a Zetasizer Nano ZS90 (Malvern Instru-
ments, Malvern, UK), and the concentration of polymer is
Fig. 3. Photography of the PDMAEMA macroscopic gel formed by the RAFT polymer-
ization at high monomer concentration (0.75 M) and AIBN as initiator.
out at the interface. In the presence of the crosslinker, there should
form a crosslinked region between the core and the shell, and result
in the formation of nanogel. The complete ionization of the
PDMAEMA segment in the product was carried out in 1 mM
phosphate buffer at pH 4 at room temperature.
0.1 mg mLꢂ1
.
3. Results and discussion
2.6. Characterization of products
The synthesis of the mPEG550-TTC macroRAFT was carried out
by the reaction of mPEG550 with TTCA under the assistant of DMAP
and DCC in toluene. Fig. 1 shows the 1H NMR spectra of the TTCA
and the as-prepared mPEG550-TTC macroRAFT agent. Comparing to
TTCA, there appears some new peaks for the product at 4.27 ppm,
which correspond to the proton of eCH2eOe(C]O), and the signal
at 3.6 ppm is assigned to the proton in the methylene of the mPEG
chain. The chemical shift of the proton of the terminal methoxyl of
the mPEG appears at 3.4 ppm. The ratios of Af: Aa: Ae: Ah ¼ 2:3:2:3,
and the results confirmed the formation of mPEG550-TTC macro-
RAFT agent [15].
1H NMR spectra were measured by a Bruker spectrometer
(Avance 300, 300 MHz) with CDCl3 or D2O as solvent. The number-
average molar mass (Mn), the weight-average molar mass (Mw),
and the molar mass distribution (Mw/Mn) were determined by
gel permeation chromatography (GPC, Waters 2410) in THF at
1.0 mL/min using PS as the standard. For dynamic laser scattering
measurement, a commercial spectrometer (ALV/DLS/SLS-5022F)
equipped with multi-
s digital time correlation (ALV5000) and
a cylindrical 22 mW UNIPHASE HeeNe laser (l0 ¼ 632 nm) as the
light source was used. The intensityeintensity time correlation
function G(2)(t,q) was measured to determine the line-width
The efficiency of mPEG550-TTC in controlling the polymerization
of DMAEMA in aqueous solution was studied, and Fig. 2 shows the
GPC trace of the as-formed copolymer mPEG550-PDMAEMA. The
distribution G(G). For diffusive relaxation, G is related to the
translational diffusion coefficient (D) of the scattering object
Fig. 4. 1H NMR spectra of the mPEG550-TTC macroRAFT agent (Curve 1), and Sample 2 in both CDCl3 (Curve 2) and D2O (Curve 3), respectively.

L. Yan, W. Tao / Polymer 51 (2010) 2161e2167
2165
Fig. 5. a) Hydrodynamic radii (Rh) and its distribution (f(Rh)) of Sample 2 (0.5 mg mLꢂ1) in water; b) Typical AFM height image of the nanogel of Sample 2 at the surface of the new
cleaved mica in air.
diblock copolymer exhibits an unimodal and narrow distribution,
and the Mn ¼ 4.7 ꢁ 103, Mw ¼ 5.1 ꢁ103 (Mw/Mn ¼ 1.1), indicating the
living radical polymerization of DMAEMA.
room temperature and freeze dried, some powder was obtained.
Elemental analysis result shows that the ratio of N:C:H of the
powder is 0.28:4.19:9.09. Then the molar ratio of mPEG and
PDMAEMA in the product can be calculated by following equation:
The as-prepared mPEG550-TTC macroRAFT agent is an amphi-
philic and could form micelles in aqueous solution. In experiment,
DMAEMA monomer, crosslinker MBA, PEG-RAFT agent and the
initiator AIBN were added into water to form a colloid of micelles
under stirring. The ratios of DMAEMA: MBA: mPEG550-TTC mac-
roRAFT agent: initiator are listed in Table 1. For Sample 1, the
concentration of DMAEMA is 0.115 g mLꢂ1, and the mixture was
heated at 65 ꢀC for 3 h for the polymerization. There formed
a macroscopic gel in yellow-light color as shown in Fig. 3, indicates
the damage of the micelles and the crosslinking of neighboring
micelles. Riger and Charleux found the similar result in the poly-
merization of DEAAm controlled by the mPEO2000-TTC macroRAFT
agent, and they suggested that the hydrophilicity of PEO2000 is too
weak to stabilize the nanogel [15]. However, for PEO2000 the
number of the repeat units is 45 while there are 12 carbons as the
hydrophobic segment, and it makes the macroRAFT more hydro-
philicity. It will be different if mPEG550-TTC macroRAFT agent was
utilized for its ratio of the hydrophilic to hydrophobic segments is
near 1. Another key factor is the concentration of monomer, and
a low concentration should be helpful for avoiding the formation of
macroscopic gel. Thereafter, a new mixture of reactants with ratio
of DMAEMA:MBA:mPEG550-TTC:initiator ¼ 6:0.2:0.28:0.042 was
prepared, and it was polymerized and crosslinked at 65 ꢀC for 3 h
(Sample 2). No apparent macroscopic gel appeared and there
obtained a homogeneous turbid emulsion. After it was dialyzed at
n=ð15n þ 80mÞ ¼ N : H
where n is the number of DMAEMA unit in the product, and m is the
number of PEG-RAFT. The calculated n:m equals 4.6 for Sample 2,
indicates the molar ratio of PDMAEMA and PEG segments in the
polymer is 4.6.
Fig. 4 shows the 1H NMR spectra of the mPEG550-TTC macroRAFT
(Curve 1) agent and the product in both D2O (Curve 2) and CDCl3
(Curve 3), respectively. The characteristic signal of the methylene
proton in PEG (w3.6 ppm) was appeared in every spectrum.
However, there appears apparent difference for the spectra
measured in D2O and CDCl3. In D2O the signal of PDMAEMA is clear
at 3.9 ppm, 3.3 ppm and 2.9 ppm, which are attributed to oxy-
methylene, azamethylene and the terminal methyl protons,
respectively [24]. But the signals are very weak in CDCl3. In addi-
tion, the area ratio of protons signal of PDMAEMA to PEG are
smaller than the values measured by elemental analysis, indicates
the mobility of the PDMAEMA chains in the products are limited.
The result revealed that there may form crosslinking of PDMAEMA
segments. The signal of the proton in PEG segment is strong,
1: PEG
2: Sample 3
2
1
4000 3500 3000 2500 2000 1500 1000 500
Wavenumber (cm-1)
Fig. 6. The chemical structure of initiator AIBN (a) and V501 (b), and the 1H-NMR
spectrum of Sample 3 in D2O (c).
Fig. 7. FT-IR spectra of pure PEG (Curve 1) and Sample 3 (Curve 2).

2166
L. Yan, W. Tao / Polymer 51 (2010) 2161e2167
25
20
15
10
5
Fig. 10. Zeta potential of Sample 3 in water.
0
1
10
100
1000
of DMAEMA monomer into the particles. Comparing with Sample 2,
the PDMAEMA segments in Sample 3 increased. Beside the differ-
ence of the hydrophilicity for AIBN and V501, the other possible key
factor is the half-life (t1/2) of the initiators, and they are 10 h for
AIBN and 29 h for V501 at 65 ꢀC. So the slow decomposition rate for
V501 may be the key point to control the polymerization of
DMAEMA, and result in the formation of small nanogels. The detail
should be studied in near future.
Fig. 7 shows the FT-IR spectra of PEG and Sample 3. Comparing
with the spectrum of pure PEG (Curve 1), the Curve 2 has the
characteristic peaks of PEG. In addition, there appears some new
peaks at 2856 cmꢂ1 for the CeH stretching of the eN(CH3)2 group,
at 1728 cmꢂ1 for the carbonyl group, at 1140 cmꢂ1 for the CeN
stretching, and at 1476 cmꢂ1 for the N-(CH3)3 deformational stretch
vibration [25], also indicate the polymerization of DMAEMA
monomer in Sample 3.
Fig. 8 shows the hydrodynamic radii (Rh) and their distribution
(f(Rh)) of Sample 3 measured by the dynamic laser scattering. The
average size of the nanogel is about 10 nm, and the distribution is
narrow. The result revealed that Pegylated nanogels of PDMAEMA
with a narrow distribution can be prepared by using V501 as the
initiator.
Fig. 9 shows the typical AFM height images of Sample 3 after
depositing its suspension onto the surface of the new cleaved mica
by a spin-coater (3000 rpm) at room temperature. There appear
many particles and the size of the particles is about 20 nm in
diameter, which is consistent with the DLS result.
2R (nm)
h
Fig. 8. Hydrodynamic radii (Rh) and its distribution (f(Rh)) of Sample 3 (0.5 mg mLꢂ1
)
in water.
indicates the free extend of PEG chains, and it suggested that the
PEG chains surround the crosslinked PDMAEMA core [23].
Fig. 5a shows the hydrodynamic radii (Rh) and their distribution
(f(Rh)) of Sample 2 measured by the dynamic laser scattering. The
polymer owns a wide distribution of size in aqueous solution, and
the major particles are in size of about 75 nm while there are some
particles in size of about 200 nm in radii. The result revealed that
there formed nanogel of PDMAEMA. However, the size of the
nanogels is in a wide distribution. Fig. 5b shows the AFM image of
the nanogels of Sample 2 on the surface of substrate, and the
particles are also in a wide distribution, and the result is consistent
with the DLS result.
AIBN is a typical hydrophobic initiator, and it may interact with
the hydrophobic core of the formed micelle and makes it unstable,
especially during the polymerization. So a more hydrophilic initi-
ator may be good to control the distribution of the size of nanogels.
Here, V501, a carboxyl modified AIBN was utilized for the prepa-
ration of Sample 3, and a mixture reactant with the ratio of
DMAEMA:MBA:mPEG550-TTC:initiator ¼ 6.4:0.26:0.24:0.27 was
prepared and polymerized. Fig. 6 shows the 1H NMR spectrum of
Sample 3 in D2O, and the signal of protons in the PEG segments are
clearly showed while the signals of protons for PDMAEMA are
weak, and the result is similar to that of Sample 2, indicates the
limitation of mobility of the PDMAEMA chains in product.
Elemental analysis measurement showed that the ratio of N:C:
H ¼ 0.32:4.27:8.87 for the as-prepared product, and the calculated
n:m equals 6.4. So in the product the molar ratio of the repeated
unit of DMAEMA to PEG is 6.4, indicates a successful polymerization
It is well known that PDMAEMA is positive, and it is expected
that the as-prepared nanogel should also be positive. Fig. 10 shows
the Zeta potential measurement of Sample 3 with a complete
ionization, and the zeta potential is þ30 mV.
4. Conclusion
Here, a simple method was reported to synthesize the Pegylated
cationic nanogel of PDMAEMA in one-step via the in situ formation
of micelle by an amphiphilic trithiocarbonate macroRAFT agent
(mPEG550-TTC). Elemental analysis, dynamic laser scattering and
atomic force microscopy studies confirmed the formation of the
nanogels of PDMAEMA, and their size depended strongly on the
monomer concentration and the kinds of initiator. The as-prepared
nanogel initiated by V501 is in size of about 10 nm in radii and its
zeta potential is about þ30 eV, which is a potential gene delivery
system for further biomedical application.
Acknowledgements
This work is supported by the National Natural Science Foun-
dation of China (No.20874095), the National Basic Research
Fig. 9. Typical AFM height images of the nanogel of Sample 3 at the surface of the new
cleaved mica in air.

L. Yan, W. Tao / Polymer 51 (2010) 2161e2167
2167
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