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Core–Shell MnSe@Bi2Se3 Fabricated via a Cation Exchange
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Method as Novel Nanotheranostics for Multimodal
Imaging and Synergistic Thermoradiotherapy
Guosheng Song, Chao Liang, Hua Gong, Meifang Li, Xianchuang Zheng, Liang Cheng,
Kai Yang,* Xiqun Jiang, and Zhuang Liu*
Radiation therapy (RT), which is an extensively used cancer
treatment strategy accompanying with surgery and chemo-
therapy, uses ionizing radiation to destruct tumors primarily
through the generation of oxygen radicals to attack biomole-
cules of importance (e.g., DNA) inside cancer cells.[1] However,
external RT using high-energy radiation (X-ray or γ-ray) to kill
cancer cells would in the meantime cause severe damages to
normal tissues which are penetrated by the radiation rays.[2]
Moreover, due to the hypoxic nature inside the tumor micro-
environment, tumor cells containing insufficient oxygen are
more resistant to ionizing radiation than normal cells, resulting
in the resistance or failure of RT.[3]
Nanomedicine to improve the efficacy and reduce toxic effects
of conventional cancer therapeutics has attracted tremendous
attentions in recent years.[4] As far as RT is concerned, tumor-
homing nanoagents with high-Z elements such as gold,[5] rare
earth elements,[6] and bismuth[7] as radiosensitizers can effec-
tively concentrate a greater local radiation dose within the
tumor, thus enhancing the RT efficacy to cancer while reducing
radiotoxicity to surrounding normal tissues.[5b,6,8] On the other
hand, new approaches with the help of nanotechnology have
also been proposed to improve the oxygenation level in the
tumor,[3b,9] such as by using manganese dioxide nanoparticles
to trigger the production of O2 from H2O2 which is enriched
in tumor microenvironment, so as to surmount hypoxia-associ-
ated radioresistance.[10] Using carefully engineered nanoagents
as multifunctional platforms, RT may be combined with other
types of therapeutic strategies, including near-infrared (NIR)
Dr. G. Song, C. Liang, H. Gong, Prof. L. Cheng,
Prof. Z. Liu
Institute of Functional Nano and Soft Materials
(FUNSOM)
Collaborative Innovation Center of Suzhou
Nano Science and Technology
Soochow University
Suzhou, Jiangsu 215123, China
E-mail: zliu@suda.edu.cn
M. Li, Prof. K. Yang
School of Radiation Medicine and Protection and School
for Radiological and Interdisciplinary Sciences (RAD-X)
Medical College of Soochow University
Suzhou, Jiangsu 215123, China
E-mail: kyang@suda.edu.cn
Dr. X. Zheng, Prof. X. Jiang
College of Chemistry and Chemical Engineering
Nanjing University
Nanjing 210093, China
DOI: 10.1002/adma.201503006
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light induced photothermal therapy (PTT), to realize combina-
tion therapy of cancer for highly effective cancer treatment.[6,11]
Despite those encouraging achievements reported in the past
1–2 years, how exactly the photothermal effect would enhance
the efficacy of RT via a synergistic manner merits careful inves-
tigation. Moreover, the synthesis of nanostructures with the
multiple imaging and therapy functions via simplified methods
are still desired for the development of imaging-guided, NIR-
triggered thermoradiotherapy.
Herein, MnSe@Bi2Se3 core–shell nanostructures are ration-
ally designed and successfully fabricated by a partial cation
exchange method, using MnSe nanocrystal as a template,
whose outer layer of manganese is replaced by bismuth to
form a Bi2Se3 shell. In this system, the paramagnetic MnSe
core offers contrasts for both T1- and T2-weighted magnetic
resonance (MR) imaging, whereas the Bi2Se3 shell endows the
nanostructure with strong absorbance of both X-ray and NIR
light, useful for computed tomography (CT) imaging, enhanced
RT, as well as PTT. It is found that the combination of RT and
PTT using MnSe@Bi2Se3 nanoparticles can bring a strong syn-
ergistic effect for the treatment of a mouse tumor model. It is
then discovered that such a synergistic treatment outcome is
owing to the remarkably increased oxygenation resulted from
the mild hyperthermia during PTT to boost the blood flow into
the tumor, enhancing the efficacy of RT for effective cancer
killing. Our work not only presents a simple cation exchange
method to fabricate core–shell nanostructures with highly inte-
grated imaging and therapy functions but also demonstrates a
promise concept to enhance conventional RT by: i) using X-ray
absorbing agents to locally concentrate radiation energy and
ii) employing NIR triggered PTT to overcome hypoxia-associated
radioresistance.
There are numerous examples for syntheses of core–shell
nanoparticles by sequential growth methods, which, however,
often contains tedious synthetic procedures and would result in
structures obviously larger than the original cores.[4e,6,12] Here
a cation exchange method was used to produce MnSe@Bi2Se3
core–shell nanostructures from pre-made MnSe nanoparticles
by simply adding a controlled amount of Bi source into a solu-
tion of MnSe (Figure 1a). Compared to manganese chalcoge-
nides, bismuth chalcogenides have a much lower solubility
(higher pKsp).[13] This will be a thermodynamic driving force
favorable for the cation exchange reaction of manganese by
bismuth.[14]
The as-prepared MnSe nanoparticles showed a bullet-like
morphology as revealed by transmission electron microscopy
(TEM) imaging (Figure 1b and inset), with an average length
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Figure 1. Synthesis and characterization of MnSe@Bi2Se3 core–shell nanoparticles. a) A scheme showing the fabrication of MnSe@Bi2Se3 core–shell
nanostructure by cation exchange and the subsequent PEGylation. TEM images of as-synthesized MnSe b) and MnSe@Bi2Se3 c) nanoparticles. Inset:
The corresponding magnified TEM images (scale bar = 50 nm). d) HAADF-STEM images of an individual MnSe@Bi2Se3 core–shell nanostructure.
The element maps showed the distribution of Mn (red), Se (yellow), and Bi (green). e) Line scan profiles recorded from a MnSe@Bi2Se3 nanoparticle.
f) Powder XRD patterns of MnSe and MnSe@Bi2Se3 nanoparticles. g) UV–vis–NIR absorbance spectra of MnSe and MnSe@Bi2Se3 nanoparticles
dispersed in chloroform at the same concentration (60 µg mL−1).

of 132 ± 19 nm and width of 105 ± 25 nm. After the bismuth
source was introduced into the reaction solution of as-made
MnSe templates, the solution temperature was slowly increased
to activate the cation exchange. The resulted MnSe@Bi2Se3
core–shell nanostructures showed well-maintained morphology
and size (length = 132 ± 21 and width = 111 ± 21 nm) (Figure 1c
and inset). The precise control/preservation of morphology and
sizes is an obvious advantage of the cation exchange method in
comparison to the conventional sequential growth method to
prepare core–shell nanoparticles.[13–15]
The successful fabrication of MnSe@Bi2Se3 core–shell
nanostructures was evidenced by the high-resolution TEM
imaging (Figure S1, Supporting Information), energy disper-
sive spectra (EDX) (Figure S2, Supporting Information), and
elemental mapping by the high-angle annular dark-field scan-
ning TEM (HAADF-STEM) (Figure 1d,e). As expected, char-
acteristic X-ray diffraction (XRD) peaks of both rhombohedral
Bi2Se3 and hexagonal MnSe crystal planes were observed in
the as-prepared MnSe@Bi2Se3 sample (Figure 1f). The above
results unambiguously reveal that those nanoparticles are com-
posed by the MnSe core together with the Bi2Se3 shell and
show a bullet-like morphology with clear boundary of core–
shell nanostructure. Moreover, after coating with the Bi2Se3
shell, the obtained MnSe@Bi2Se3 core–shell nanoparticles
exhibited greatly enhanced optical absorption from visible to
NIR region, in marked contrast to bare MnSe core nanoparti-
cles which showed light yellow color with little absorbance at
longer wavelengths (Figure 1g). As determined by inductively
coupled plasma atomic-emission spectroscopy (ICP-AES) meas-
urement, the exact molar ratio of Mn and Bi was 1:1.97 for our
MnSe@Bi2Se3 nanoparticles. Note that for MnSe nanoparticles
with the current size, even if excess Bi source was added, the
internal MnSe core still could not be fully replaced by Bi2Se3
(Figure S3, Supporting Information).
Next, we would like to functionalize as-made oleylamine
capped MnSe@Bi2Se3 nanoparticles to make them soluble in

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water and stable in physiological solutions. An amphiphilic
polymer, PEG-grafted poly(maleicanhydride-alt-1-octadecene)
(C18PMH-PEG), was introduced to coat those nanoparticles
by hydrophobic interaction.[16] The resulted PEG modified
MnSe@Bi2Se3 (MnSe@Bi2Se3-PEG) exhibited excellent dis-
persity in various solutions including water, phosphate buff-
ered saline (PBS), and cell culture medium, without showing
any agglomeration as evidenced by the consistent diameters
(≈140 nm) measured by dynamic light scattering (DLS) (Figure S4,
Supporting Information). The zeta potential of MnSe@Bi2Se3-
PEG nanoparticles was measured to be −3.25 ± 1.32 mV in cell
culture medium.
The X-ray attenuation agents usually containing high-Z
elements are able to produce contrasts in CT imaging.[17] Bis-
muth has a higher X-ray attenuation coefficient compared to
several stable nonradioactive heavy elements such as I, W, Au,
and Ta used in CT imaging.[7,18] The CT images of MnSe@
Bi2Se3-PEG aqueous solutions thus showed a sharp signal
enhancement as the increase of Bi concentrations (Figure S5,
Supporting Information). The slope of Hounsfield units (HU)
for MnSe@Bi2Se3-PEG (≈5.85 HU mM−1) appeared to be
higher than that of a clinically used CT contrast agent (Iohexol,
≈4.48 HU mM−1) (Figure 2a). The excellent CT signal enhance-
ment ability of MnSe@Bi2Se3-PEG encouraged us to further
use it for in vivo CT imaging. In our experiments, 4T1 murine
breast tumors growing on Balb/c mice were injected with a
solution of MnSe@Bi2Se3-PEG (10 mg kg−1). Animal experi-
ments were carried out under protocols approved by Soochow
University Laboratory Animal Center. As revealed by in vivo CT
imaging (Figure 2b), a strong contrast showed up in the tumor
upon injection of nanoparticles, with the HU value increased
from ≈50.4 to ≈126.2 HU, suggesting the great CT contrasting
efficiency of MnSe@Bi2Se3-PEG.
Magnetic resonance (MR) imaging possesses excellent spa-
tial resolution and is more sensitivity than CT imaging.[19]
Mn2+ with five unpaired 3d electrons is known to be a contrast
agent in T1-weighted MR imaging.[20] Encouragingly, with the
increase of MnSe@Bi2Se3-PEG concentrations, the acquired
MR images became brighter under the T1-weighted mode,
while gradually turned darker under the T2-weighted mode
(Figure S5, Supporting Information). The corresponding lon-
gitudinal relaxivity (r1) and transverse relaxivity (r2) of MnSe@
Bi2Se3-PEG were measured to be r1 = 5.44 mM−1 s−1, and r2 =
27.6 mM−1 s−1, respectively (Figure 2c), which were comparable
to manganese oxide nanoparticles.[21] Although being encapsu-
lated inside the Bi2Se3 shell, the paramagnetic MnSe core still
could induce the effective shortening of T1 relaxation of sur-
rounding water protons, similar to many other magnetic nano-
particles shelled by Au, SiO2, CuS2−x, or TaOx coatings.[6,12a,22]
Then, the contrast enhancing effect in vivo was evaluated in
Balb/c mice bearing 4T1 tumors before and after injection of
MnSe@Bi2Se3-PEG (10 mg kg−1) (Figure 2d). For T1-weighted
MR imaging, the tumor became brighter and showed marked
positive enhancement, while the T2-weighted images showed
negative contrast in the tumor after injection of nanoparticles,
demonstrating the capability of MnSe@Bi2Se3-PEG to serve as

Figure 2. CT and MR imaging with MnSe@Bi2Se3-PEG. a) HU values of MnSe@Bi2Se3-PEG or Iohexol solutions at different concentrations under CT
imaging. b) CT images of a 4T1 tumor-bearing mouse before (up) and after (down) injection with MnSe@Bi2Se3-PEG. The CT contrast was obviously
enhanced in the mouse tumor after nanoparticle injection. c) T1 relaxation rate (1/T1) and T2 relaxation rate (1/T2) of MnSe@Bi2Se3-PEG solutions
measured as the function of Mn2+ concentrations. d) T1-weighted MR images (up) and T2-weighted MR images (down) of a 4T1 tumor-bearing mouse
before (left) and after (right) injection with MnSe@Bi2Se3-PEG. Our nanoparticles offered strong contrasts in the tumor under both T1-weighted and
T2-weighted MR imaging modes.

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Figure 3. In vitro PTT and enhanced RT. a) Confocal fluorescence images of 4T1 cells treated with PBS, NIR, MnSe@Bi2Se3-PEG, and MnSe@Bi2Se3-
PEG + NIR. Live and dead cells were stained by Calcein AM and PI and presented in green and red colors in those images, respectively. b) Imaging
of the marker (γ-H2AX) for double-strand DNA breaks in 4T1 cells treated with PBS, RT (4 Gy), MnSe@Bi2Se3-PEG, and MnSe@Bi2Se3-PEG + RT
(4 Gy). Cells exposed to nanoparticles after RT exhibited the highest level of DNA damage (positive in γ-H2AX). c) Clonogenic survival assay of 4T1
cells treated with and without MnSe@Bi2Se3-PEG under series of radiation doses at 0, 2, 4, and 6 Gy. The error bars represent the standard error of
mean of at least three replicates. P values: *P < 0.05, **P < 0.01.

the contrast agent for both T1- and T2-weighted MR imaging.
Notably, the integration of T1- and T2-weighted MR modes in
a single nanoagent may potentially enhance the ability of dis-
criminating hypointense tissue in MR imaging, to overcome
the intrinsic shortcoming of the T2-weighted mode.[12a]
Our MnSe@Bi2Se3-PEG exhibited no obvious adverse effects
to the viabilities of 4T1 and HeLa cells at tested concentrations
from 1.56 to 100 µg mL−1 for 24 h, as evaluated by the methyl
thiazolyl tetrazolium (MTT) assay (Figure S6, Supporting Infor-
mation). With strong NIR absorbance contributed by the topo-
logical insulator Bi2Se3 shell,[18a] effective photothermal heating
of MnSe@Bi2Se3-PEG could be induced upon irradiation by
the 808 nm NIR laser (Figures S7 and S8, Supporting Informa-
tion). Those MnSe@Bi2Se3-PEG nanoparticles also possessed
excellent photothermal stability without significantly losing
their absorbance after multiple rounds of NIR laser irradiation
(Figure S9, Supporting Information). Therefore, as expected,
4T1 cancer cells incubated with MnSe@Bi2Se3-PEG could
be effectively ablated by the NIR laser (808 nm, 1 W cm−2)
(Figure 3a).
Next, we wondered whether MnSe@Bi2Se3-PEG with strong
X-ray attenuation ability would be able to enhance RT trig-
gered by ionizing radiation such as X-ray. 4T1 cells were incu-
bated with either phosphate buffered saline (PBS) or MnSe@
Bi2Se3-PEG (40 µg mL−1) and then exposed to X-ray radiation
at a dose of 4 Gy. Cells were then immunofluorescently labeled
for γ-H2AX, a marker of double-strand DNA breaks, to evaluate
DNA damage in cancer cells induced by RT (Figure 3b). While
our nanoparticles by themselves induced no detectable DNA
damage to cells, a remarkably enhanced DNA damage level
induced by X-ray was observed for cells treated with MnSe@
Bi2Se3-PEG in comparison to the PBS control, suggesting the
strong RT enhancement effect of those Bi-containing nanopar-
ticles. In addition to the DNA damage assay, the clonogenic sur-
vival assay was also conducted to evaluate the in vitro efficacy
of RT (Figure 3c). The group treated with MnSe@Bi2Se3-PEG
showed much lower percentages of viable cell colonies than that
without nanoparticle treatment, at the same X-ray irradiation
doses. By using a linear-quadratic model to analyze enhance-
ment of radiation effects,[8] the sensitizing enhancement ratio
of MnSe@Bi2Se3-PEG was calculated to be ≈1.16, which is
comparable to gold nanoparticles as a radiosensitizer.[8,23] These
results confirmed that MnSe@Bi2Se3-PEG could increase X-ray
induced DNA damage and thus enhance the efficacy of RT to
inhibit the proliferation of cancer cells, likely due to MnSe@
Bi2Se3-PEG nanoparticles inside cells to absorb and concentrate
the radiation dose toward those cells.[6,8]
After demonstrating the capability of MnSe@Bi2Se3-PEG to
trigger PTT and enhance RT in vitro, we then would like to use
these nanoparticles for in vivo cancer treatment in a mouse tumor
model. Balb/c mice bearing subcutaneous 4T1 tumors were
intratumorally injected with MnSe@Bi2Se3-PEG (4 mg kg−1),
and then irradiated with the 808 nm laser (0.6 W cm−2). As
monitored by a IR thermal camera, after 20 min of NIR irra-
diation, the temperature of tumors injected with MnSe@Bi2Se3-
PEG increased to ≈45 °C, while those injected with PBS were
not notable heated (final temperature ≈ 36 °C) (Figure 4a,b).
To study the in vivo efficacy of PTT, enhanced RT, and the
combination of PTT and RT induced by MnSe@Bi2Se3-PEG, a
total of seven groups of mice were used in our experiments:
Group 1: PBS; Group 2: PBS + NIR; Group 3: MnSe@Bi2Se3-
PEG; Group 4: X-ray irradiation without nanoparticle injection
(RT alone); Group 5: MnSe@Bi2Se3-PEG + NIR (PTT); Group 6:
MnSe@Bi2Se3-PEG + X-ray (enhanced RT); Group 7: MnSe@
Bi2Se3-PEG + NIR + X-ray (PTT + enhanced RT). The nano-
particle dose was (4 mg kg−1) in all groups. The tumor growth
curves and representative photographs of mice from different
groups were shown in Figure 4c and Figure S10 (Supporting
Information), respectively. As expected, neither NIR irradiation
nor MnSe@Bi2Se3-PEG injection showed appreciable effect
on tumor growth. The mild PTT treatment with injection of
MnSe@Bi2Se3-PEG followed by NIR irradiation (0.6 W cm−2)

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Figure 4. In vivo combined cancer treatment with MnSe@Bi2Se3-PEG. a) IR thermal images of 4T1 tumor-bear mice with injection of PBS or MnSe@
Bi2Se3-PEG (dose = 4 mg kg−1), under the 808 nm laser irradiation (0.6 W cm−2). b) Temperature changes of tumors monitored by the IR thermal camera
during laser irradiation. c) Tumor volume growth curves of mice after various treatments (five mice for each group). NIR irradiation was conducted
by the 808 nm laser at 0.6 W cm−2 for 20 min and the radiation dose used for RT was 4 Gy. Statistical analysis was performed using the Student's
two-tailed t-test (*P < 0.05 and **P < 0.01).

(Group 5) was able to partially inhibit the tumor growth, with
the overall tumor growth inhibition (TGI) ratio determined to
be ≈38%. Compared with RT alone (Group 4) (TGI ≈ 23%),
injection of MnSe@Bi2Se3-PEG plus X-ray irradiation (Group
6) induced more significant tumor growth inhibition (TGI ≈
41%, P < 0.05), suggesting the ability of MnSe@Bi2Se3-PEG to
enhance the efficacy of in vivo RT. Most importantly, a remark-
able tumor growth inhibition efficiency (TGI ≈ 90%) was
observed for the tumors treated by MnSe@Bi2Se3-PEG + NIR +
RT (Group 7), demonstrating the synergistically enhanced ther-
apeutic effect by such combined PTT and RT therapy. Micro-
scopy images of hematoxylin and eosin (H&E) stained and ter-
minal deoxynucleotidyl transferase-mediated dUTP-biotin nick
end labeling (TUNEL) stained tumor slices also uncovered that
the combined PTT and RT triggered by MnSe@Bi2Se3-PEG
(Group 7) exerted the most significant damages to tumor cells
(Figure S11, Supporting Information).
The presence of hypoxic tumor cells in tumor micro-
environment is one of the main reasons of resistance to
RT.[3] The effect of ionizing radiation can be largely increased
under well-oxygenated conditions compared with treatment
of hypoxic tumors.[3b,9a,24] To examine the effect of mild PTT
on the tumor hypoxia, the in vivo imaging of tumor hypoxia
was performed with a recently reported fluorescence probe,
poly(N-vinylpyrrolidone)-conjugated iridium (III) complex (Ir-
PVP).[25] The phosphorescence emission of Ir-PVP is quenched
by oxygen in normal tissues but could be turned on when the
oxygen content is reduced, providing hypoxia specificity during
fluorescence imaging.[25] The mixture of Ir-PVP + MnSe@
Bi2Se3-PEG showed no obvious fluorescence change after NIR
irradiation, indicating the great stability of this fluorescent
probe during PTT (Figure S12, Supporting Information). Mice
bearing subcutaneous 4T1 tumors were intratumorally injected
with Ir-PVP or a mixture of Ir-PVP + MnSe@Bi2Se3-PEG. From
the whole body imaging (Figure 5a,b), the tumors treated with
MnSe@Bi2Se3-PEG + NIR showed obviously decreased fluores-
cence intensity post-NIR irradiation. In contrast, the fluores-
cence intensities in tumors treated with MnSe@Bi2Se3-PEG
without NIR irradiation or NIR irradiation alone remained
unchanged. Therefore, the oxygenation of tumor hypoxia was
improved immediately after NIR irradiation.
To further confirm the ability of mild PTT to overcome
hypoxia in vivo, hypoxyprobe (pimonidazole) immuno-histo-
chemical assay was performed for tumor slices post different
treatments.[3a,26] Images of immunoperoxidase stained tumor
slices revealed that PTT treatment induced by MnSe@Bi2Se3-
PEG + NIR could largely reduce the hypoxic level in almost the
whole tumor (Figure 5c). Immunofluorescence staining assay
was further carried out by staining the cell nuclei, blood vessels,
and hypoxia areas with 2-(4-amidinophenyl)-6-indolecarbami-
dine dihydrochloride (DAPI) (blue), anti-CD31 antibody (red),
and antipimonidazole antibody (green), respectively (Figure 5d).

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Figure 5. Effect of NIR-induced PTT on tumor hypoxia. a) Whole-body fluorescence imaging of mice bearing subcutaneously 4T1 tumors with i.t.
injection of tumor hypoxia fluorescence probe Ir-PVP, or a mixture of Ir-PVP + MnSe@Bi2Se3-PEG. The images were taken before and after NIR irradia-
tion. b) The relative fluorescence intensities of Ir-PVP in tumors for different groups of mice at different time points after NIR irradiation. P values: *P
< 0.05. c) Immunoperoxidase staining by the hypoxyprobe for tumor slices without (left) or with (right) MnSe@Bi2Se3-PEG induced PTT treatment.
d) Representative immunofluorescence images of tumor slices. The nuclei, blood vessels, and hypoxia areas were stained with DAPI (blue), anti-CD31
antibody (red), and antipimonidazole antibody (green), respectively.

Consistent to immunoperoxidase staining results, the tumor
treated with MnSe@Bi2Se3-PEG + NIR showed obviously weak-
ened pimonidazole-stained (green) hypoxic area compared to
the control group, indicating that the tumor hypoxia was effec-
tively reduced by mild hyperthermia. More interestingly, for
tumor tissues nearby blood vessels identified by CD31 staining
(red), the hypoxia situation was greatly reversed, suggesting
that the mild PTT may enhance blood flow into the tumor and
then improve the tumor oxygenation.[3,27] Therefore, the overall
tumor oxygenation status could be improved immediately after
PTT, decreasing the hypoxia-associated radioresistance,[1b,27a,28]
and thus resulting in excellent synergistic therapeutic effects
achieved by the combined PTT and RT.
Bismuth is considered to have low toxicity among heavy ele-
ments.[7] Some Bi-containing compounds could be gradually
metabolized by the liver.[7] To investigate whether MnSe@Bi2Se3-
PEG would result in any side effect, blood chemistry, complete
blood panel analysis, and histology examination were carried out
for healthy mice after intravenous injection of MnSe@Bi2Se3-PEG
(10 mg kg−1), at the 1st, 7th, 14th, and 28th day post-injection
(Figure S13, Supporting Information). Encouragingly, most of
measured parameters are rather close to those of untreated healthy
mice and fell within the normal reference ranges. Moreover, no
noticeable tissue damage and adverse effect to major organs was
observed from the H&E stained organ slices (Figure S14, Sup-
porting Information). Our preliminary data showed no obvious
clue of toxicity induced by MnSe@Bi2Se3-PEG to the treated mice.
Nevertheless, further careful studies are still required to system-
atically look into the long-term biodistribution, excretion, and toxi-
cology behaviors of those nanoparticles in animals.

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In conclusion, we have used the cation exchange method
for the synthesis of multifunctional MnSe@Bi2Se3 core–shell
nanostructures. During cation exchange, those core–shell nano-
particles show well-preserved size and morphology without size
expansion and interior composition mixing. This nanoscale
cation exchange reaction is able to produce novel nanomaterials
with multicomponent compositions and structures that are
not easily accessed by traditional sequential growth methods.
In such MnSe@Bi2Se3 system, the paramagnetic MnSe core
offers contrasts for both T1- and T2-weighted MR imaging,
while the Bi2Se3 shell endows the nanostructure with the ability
of absorbing ionizing radiation useful for CT imaging and
enhanced RT as well as high NIR optical absorbance to enable
PTT. Using MnSe@Bi2Se3-PEG as the multifunctional agent,
the efficacy of RT could be enhanced not only by the nanopar-
ticles in the tumor to concentrate radiation energy but also by
the mild PTT triggered by the NIR laser to improve the oxy-
genation level in the tumor to overcome hypoxia-associated
radioresistance. Our work, on the one hand, presents an inter-
esting cation exchange approach to construct multifunctional
theranostic nanostructures, and on the other illustrates a prom-
ising concept to enhance the efficacy of RT using nanoagents
absorbing both ionizing radiation and NIR optical light, so as to
achieve synergistic therapeutic outcomes via the combination
therapy.
Supporting Information
Supporting Information is available from the Wiley Online Library or
from the author.
Acknowledgements
This work was partially supported by the National Natural Science
Foundation of China (Grant Nos. 51302180, 51222203, 51002100,
and 51132006), the National “973” Program of China (Grant Nos.
2011CB911002 and 2012CB932601), a Project Funded by the Priority
Academic Program Development of Jiangsu Higher Education
Institutions, and Postdoctoral science foundation of China (Grant Nos.
2014M561706 and 2013M531400).
Received: June 22, 2015
Revised: July 15, 2015
Published online: September 2, 2015
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