Hybrid Assemblies for Enhanced MRI Contrast Agents
COMMUNICATION
persity of the assemblies. The solution density 1 of the as-
larger as in water, but remained constant over a period of
3 d (Figures S10 and S11). The Rg/Rh value is, within experi-
mental error, the same as in pure water, which indicates that
the PHSAM/GdW assemblies prepared in pure water or in a
150 mm solution of NaCl have a similar structure, although
the solution density is calculated to be somewhat smaller
with 1=0.15.
It has been reported that Gd-POMs can accelerate the re-
laxation of water protons owing to the accommodation of
paramagnetic Gd3+ ions in its framework, and thus, can
serve as MRI contrast agents.[6] The contrast ability of Gd-
POMs is influenced by several factors, such as molecular
size, ambient hydrophobicity, and self-assembly behavior.[12]
To investigate the influence of the microenvironment of
PHSAM/GdW assemblies on the contrast ability of GdW,
we compared the in vitro T1-weighted MR images of GdW
and PHSAM/GdW assemblies by using a clinical 1.5 T MR
scanner at room temperature. As shown in row a in
Figure 5, the images of GdW in water gradually become
semblies may be estimated to 1=0.25 gcmÀ3 by utilizing 1=
3
3M /
N
Rh =70 nm, and NA =Avogadro number. Thus, the structures
are swollen by approximately a factor of 4 by water, which
allows bulk and GdW-coordinated water to exchange.
To further confirm the electrostatic interaction between
PHSAM and GdW in the assemblies, X-ray photoelectron
spectroscopy (XPS) was used to study the dry assemblies de-
posited on a silicon substrate. As shown in the N 1s spectra
(Figure 4a), the binding energy of the nitrogen atoms of
Figure 4. a) Contrast N 1s XPS spectra of PHSAM and PHSAM/GdW as-
semblies and b) contrast W 4f XPS spectra of GdW and PHSAM/GdW
assemblies. The r values of all the assemblies are 0.5.
PHSAM is about 401.2 eV, corresponding to the ammonium
bromide groups on the side chains of PHSAM. In contrast,
the assemblies with r=0.5 exhibit a new peak of N 1s be-
sides 401.2 eV, appearing at a relatively low binding-energy
position of 399.3 eV, which should be ascribed to the ammo-
nium groups electrostatically interacting with GdW clusters.
Since the charge ratio of GdW to PHSAM is 0.5 in the as-
semblies, only half of the positive charge of PHSAM is neu-
tralized by GdW. Therefore, it is reasonable to observe both
the free and the electrostatically bound ammonium groups
in XPS spectra. On the other hand, in previous works we
have found that the electrostatic encapsulation of tungsten-
containing POMs by cationic surfactants can induce the
W 4f peaks of POMs to shift to low-binding energy position,
because the d1 electrons in POMs become more difficult to
delocalize.[11] For the PHSAM/GdW assemblies, a similar
shift of the W 4f peaks was also observed in comparison
with the pristine GdW (Figure 4b), which is another evi-
dence for the electrostatic interaction between GdW and
PHSAM.
In general, the stability of electrostatic assemblies is sensi-
tive to the ionic strength of the ambient environment. In-
creasing the ionic strength can weaken the electrostatic in-
teraction and destruct the assemblies. Therefore, it is impor-
tant to evaluate the stability of PHSAM/GdW assemblies in
a physiological environment containing abundant types of
ions. For this purpose, we prepared PHSAM/GdW assem-
blies in an isotonic salt solution (150 mm NaCl). SLS results
revealed the assemblies with r=0.5 to be stable. The molar
mass increased to Mw =300ꢁ106 gmolÀ1, the Rh and Rg
values were both determined to 90 nm, also being somewhat
Figure 5. In-vitro T1-weighted MR images of a) the aqueous solutions of
GdW, b) the aqueous solutions, and c) the 150 mm solutions of PHSAM/
GdW assemblies in NaCl with r=0.5.
brighter with increasing concentration, which demonstrates
the contrast ability of GdW. Enhanced contrasts are also ob-
served for the PHSAM/GdW assemblies with r=0.5 either
in pure water or in the aqueous 150 mm solution of NaCl
(row b and c in Figure 5) when the concentration of the as-
semblies is increased, indicating that the contrast ability of
GdW is well maintained in the assemblies. It should be
noted that the Rh values of the assemblies are stable in the
varied concentration range (Figures S9 and S12). More im-
portantly, the assemblies exhibit obviously brighter contrast
images than the pristine GdW, which is consistent with the
measured r1 of GdW and PHSAM/GdW assemblies that are
4.6 and 13.7 mmÀ1 SÀ1, respectively (Figure S13). Thus, the
relaxivity of GdW is enhanced about 3 times in the assem-
blies. It has been reported that polymer micelles loaded
with the clinically used gadopentetic acid (4.1 mmÀ1 SÀ1) also
showed a much higher relaxivity (48 mmÀ1 SÀ1) than the free
gadopentetic acid, because the restricted local motion of ga-
dopentetic acid led to a prolongation of the rotational corre-
lation time.[13] Therefore, we infer that the relaxivity en-
hancement of PHSAM/GdW assemblies is attributed to the
Chem. Eur. J. 2013, 19, 13317 – 13321
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