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Accepted Article

Title: Aggregation-Induced Emission Gold Clustoluminogens for

Enhanced Low-Dose X-ray-Induced Photodynamic Therapy

Authors: Wenjing Sun, Li Luo, Yushuo Feng, Yuting Cai, Yixi Zhuang,
Rongjun Xie, Hongmin Chen, and Xiaoyuan Chen

This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201908712

Angew. Chem. 10.1002/ange.201908712

Link to VoR: http://dx.doi.org/10.1002/anie.201908712

http://dx.doi.org/10.1002/ange.201908712
Angewandte Chemie International Edition 10.1002/anie.201908712

Aggregation-Induced Emission Gold Clustoluminogens for

Enhanced Low-Dose X-ray-Induced Photodynamic Therapy

Wenjing Sun, Li Luo, Yushuo Feng, Yuting Cai, Yixi Zhuang, Rong-Jun Xie, Xiaoyuan
Chen*, Hongmin Chen*

Accepted Manuscript
W. Sun, L. Luo, Y. Feng, Dr. H. Chen
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center
for Molecular Imaging and Translational Medicine
School of Public Health
Xiamen University
Xiamen 361102, China
E-mail: hchen@xmu.edu.cn

Y. Cai, Dr. Y. Zhuang, Dr. R. Xie

College of Materials
Xiamen University
Xiamen 361005, China

Dr. X. Chen
Laboratory of Molecular Imaging and Nanomedicine
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
National Institutes of Health (NIH)
Bethesda, MD 20892, USA
E-mail: shawn.chen@nih.gov

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Angewandte Chemie International Edition 10.1002/anie.201908712

Abstract
Radiotherapy is highly effective against solid tumor with high doses of radiation. The
use of gold nanoparticles as radiosensitizers is an effective way to boost the killing
efficacy while drastically limiting the received dose and reducing the possible damage
to normal tissues. Herein, we designed aggregation-induced emission gold
clustoluminogens (AIE-Au) to achieve efficient low-dose X-ray-induced

Accepted Manuscript
photodynamic therapy with negligible side effects. The aggregations of glutathione-
protected gold clusters (GCs) assembled by cationic polymer enhanced X-ray-excited
optical luminescence by 5.2-fold. Under low-dose X-ray irradiation, AIE-Au strongly
absorbed X-rays and efficiently generated hydroxyl radicals, which enhanced the
radiotherapy effect. Additionally, AIE-Au converted X-rays to optical luminescence,
which excited the conjugated photosensitizers, resulting in a photodynamic therapy
effect. The in vitro and in vivo experiments demonstrated that AIE-Au
clustoluminogens effectively triggered the generation of reactive oxygen species with
an order-of-magnitude reduction in the X-ray dose, enabling highly effective cancer
treatment via the unique X-PDT mechanism.

Keywords
Aggregation-induced emission, Au clustoluminogens, X-ray-induced photodynamic
therapy, radiotherapy, radiosensitizers

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Angewandte Chemie International Edition 10.1002/anie.201908712

X-ray has a high penetration depth in the human body and has been widely used in
clinical tumor imaging and therapy. As a powerful therapeutic methodology used for
over a century, radiotherapy (RT) is a leading cancer treatment approach that addresses
the needs of more than 70% cancer patients.[1] Despite such advances, it is still
challenging to use RT alone to eradicate tumor cells due to its toxic effects on normal
tissues and the radioresistance of cancer cells.[2]

Accepted Manuscript
One way to meet the current challenges in RT is developing potential radiosensitizers,
which can locally increase the radiation damage to the cells. Typical radiosensitizers
are high-Z elements that can strongly absorb, scatter, and reemit radiation energy,
resulting in a local radiation dose increase when they accumulate in tumors.[3] For
example, hafnium dioxide (HfO2) nanoparticles (NBTXR3) have been in clinical trials
in Europe since 2012 for various cancers,[4] and recently used in US to treat
hepatocarcinoma [NCT02721056]. Among the emerging potential radiosensitizers,
gold (Au) nanoparticles are particularly attractive due to their strong interaction with
radiation, excellent chemical stability and inertness, and high biocompatibility.[5]
Although radiosensitizers have the potential to enhance the RT effect, more effort is
still needed to decrease the toxic effects on normal tissues due to the use of high X-ray
doses (50–70 Gy).[1a]
Since the conception of X-ray-induced photodynamic therapy (X-PDT), in vitro and in
vivo investigations have demonstrated that X-PDT combines the advantages of both RT
and PDT for treating deep-penetrating tumors.[6] We and others have reported on a
series of photosensitizer-loaded nanosensitizers to convert X-rays to optical
luminescence, and achieve the synergistic effects of RT and PDT under low-dose X-
ray irradiation.[7] These nanosensitizers include rare-earth element based inorganic
scintillators,[7a, 7b, 7e] nanoscale metal-organic frameworks or layers,[7d] and inorganic
persistent luminescent nanoparticles.[7c, 7f] As a typical radiosensitizer, Au clusters (GCs)
represent a new type of luminescent nanomaterial to achieve enhanced RT with low
cytotoxicity.[5] Recent studies revealed that protein-protected GCs emit X-ray-excited
optical luminescence (XEOL) under X-ray irradiation[8] and could also be used as a

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Angewandte Chemie International Edition 10.1002/anie.201908712

contrast agent for imaging.[9] Herein, we designed photosensitizer-conjugated

aggregation-induced emission heterogeneous Au clustoluminogens (AIE-Au) by
employing glutathione-protected GCs to achieve efficient low-dose X-PDT with minor
side effects (Scheme 1). The glutathione-protected GCs formed heterogeneous Au
clustoluminogens (AIE-GCs), which enhanced emissions by 3.1-fold under UV
excitation (Schemes 1a, b). Under low-dose X-ray irradiation, the AIE-Au strongly

Accepted Manuscript
absorbed X-rays to generate hydroxyl radicals, which enhanced the RT effect by
damaging double-stranded DNA. Additionally, the AIE-Au efficiently converted X-
rays to optical luminescence and excited the conjugated photosensitizers, which
induced a PDT effect by oxidizing lipid membranes (Scheme 1c). The AIE-Au
clustoluminogens triggered the generation of reactive oxygen species (ROS) with an
order-of-magnitude reduction in the X-ray dose and enabled highly effective cancer
treatment via the unique X-PDT mechanism.
Fluorescent GCs were synthesized using glutathione as a protector.[10] As revealed by
transmission electron microscopy (TEM), the size of the GCs was 2.5 ± 0.6 nm (Figure
1a). Using a cationic polymer poly (allylamine hydrochloride) (PAH)-mediated
approach, GCs self-assembled into AIE clustoluminogens (AIE-GCs) with a size of
65.6 ± 0.8 nm (Figure 1b).[11] Elemental mapping analysis indicated that the AIE-GCs
contained an abundant amount of Au and sulfur (S) elements (Figure 1c). The oxidation
states of the Au on the GCs and AIE-GCs were determined by X-ray photoelectron
spectroscopy (XPS). Our results indicated that approximately 16.1% of the Au(I)
present on the surface of GCs stabilized the Au clustoluminogen core (Figure S1). After
forming the aggregates, the AIE-GCs showed a decreased Au(I) percentage
(approximately 6.6%), indicating the presence of more atomic Au species in these
nanocluster-aggregations, which induced a stronger luminescence (Figure 1d).[12] The
cationic polymer-mediated AIE process is made through Au NC cross-linking, which
strongly affects the ligand-to-metal charge transfer, and the cationic polymers with high
molecular weight achieved enhanced AIE.[13] Higher molecular weight leads to more
binding of Au NCs per chain and increases the electrostatic interactions between Au

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Angewandte Chemie International Edition 10.1002/anie.201908712

NCs.[11] However, more detailed theoretical calculations will be needed to further

understand the relationship between the electronic structure of Au NCs and the AIE
phenomenon.[14] The hydrodynamic diameters and surface charges of the GCs and AIE-
GCs were 3.1 ± 0.6 nm and 93.2 ± 1.3 nm, and -27.8 mV and +50.1 mV, respectively
(Figures S2, S3). Under X-ray irradiation, both GCs and AIE-GCs showed XEOL at a
peak of 570 nm, and AIE-GCs showed a 5.2-fold enhancement in fluorescence (Figure

Accepted Manuscript
1d), which was similar to the luminescence under UV excitation (Figure S4). The
XEOL was similar to the absorption of rose bengal (termed RB, a clinically used
photosensitizer containing four iodine (I) atoms with an absorbance at 570 nm) (Figure
S5).[15] RB was then conjugated to GCs (RB-GCs) by EDC/NHS chemistry (Figure
1e),[16] which had no effects on the size and dispersibility. After the same AIE process,
RB-GCs self-assembled into AIE Au clustoluminogens (AIE-Au) (Figure 1f).
Elemental mapping analysis confirmed that the AIE-Au contained Au, S, and I elements,
indicating the successful conjugation of RB molecules (Figure 1g). To achieve an
enhanced tumor-targeting ability, integrin recognizing RGD peptide was then
conjugated onto AIE-Au (term as R-AIE-Au) by EDC/NHS chemistry (Figure 1h).[17]
The size of RB-GCs, AIE-Au, and R-AIE-Au were 2.9 ± 0.2 nm (Figure 1e), 65.2 ±
3.2 nm (Figure 1f), and 68.2 ± 6.4 nm (Figure 1h), respectively. The modifications
were confirmed by the changes of hydrodynamic diameters, surface charges, and
absorption spectra (Figures S2, S3, S6). The R-AIE-Au nanosensitizer dispersion in
various media exhibited good colloidal stability under physiological conditions during
storage for at least one week (Figure S7). In addition, the RB loading efficiency in AIE-
Au was about 217 μg·mg−1, and the large amount of RB molecules in AIE-Au enable
fluorescence imaging (Figure S8). Moreover, high-Z elements (I atoms of RB and Au
atoms) in AIE-Au enhanced X-ray absorption that can be used for both computed
tomography (CT) imaging and radiosensitization (Figure S9).
After the successful design of AIE-Au, the performance of X-PDT in solution was
evaluated using 9,10-anthracenediyl-bis (methylene) dimalonic acid (ABDA) as the
singlet oxygen (1O2) probe. The methylene blue (MB) was used to determine the

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Angewandte Chemie International Edition 10.1002/anie.201908712

presence of hydroxyl radicals. Under X-ray irradiation (1 Gy), the absorbance of ABDA
and MB in the AIE-Au group decreased dramatically; however, the controls showed
minimal changes (Figures 2a, S10). These results indicated that AIE-Au efficiently
generated 1O2 and hydroxyl radicals under low-dose X-ray irradiation.
Next, we tested X-PDT and the enhanced RT effect by AIE-Au and Au
radiosensitization after X-ray irradiation in cancer cells in vitro. We first investigated

Accepted Manuscript
the uptake efficiency of the nanosensitizers in human glioblastoma (U87MG) cells. As
shown in Figure S11, the fluorescence signal in cells was weak in control groups,
indicating few nanosensitizers were ingested by U87MG cells. After surface-
conjugation of RGD peptides, both RB-GCs-RGD and R-AIE-Au showed significantly
enhanced cell uptakes which were confirmed by the enhancement of the fluorescence
signals in both cells and blocking experiments (Figure S11). We then investigated the
cytotoxicity of the nanosensitizers via a 4-nitrophenyl chloroformate 3-(4,5-
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. As shown in
Figures 2b and S12, there was no significant effect on cell viability at concentrations
up to 400 µg/mL, which indicated good biocompatibility of the nanosensitizers. Under
X-ray irradiation (1 Gy), the R-AIE-Au induced significant cytotoxicity with a half
maximal inhibitory concentration (IC50) value of 304.8 ± 2.6 μg/mL. Under the same
condition (Au: 60 μg/mL; incubation for 24 h; X-ray: 1 Gy), X-PDT using R-AIE-Au
substantially decreased cell viability; however, RT using R-AIE-GCs had little effect
on cell viability (Figure S12).
As compared with controls, strong green fluorescence of 1O2 probes and almost
complete cell death confirmed by using live/dead double-staining assays were observed
only in cells treated with R-AIE-Au and X-ray irradiation (Figures 2c, 2d, S13, S14).
Then, the underlying mechanism of R-AIE-Au mediated X-rays-induced cancer cells
killing was investigated systematically. After X-ray irradiation, the level of lipid
peroxidation increased to 255.0 ± 10.7%, 194.3 ± 11.3%, and 146.4 ± 19.6% for R-
AIE-Au, AIE-GCs, and PBS, respectively (Figure 2e). This indicated that X-PDT
generated more 1O2, resulting in increased oxidation of cell membranes. The

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Angewandte Chemie International Edition 10.1002/anie.201908712

radiosensitization effect was evaluated by single cell electrophoresis (i.e., comet assay).
Both the AIE-GCs-mediated RT and X-PDT groups induced a high frequency of strand
breaks, forming a long comet-like appearance (Figure 2f). The AIE-Au nanosensitizer
has high absorption coefficient and energy deposition for X-ray irradiation. Therefore,
upon a low-dose of X-ray, the gold clusters in AIE-Au could be excited to produce
enhanced-radiotherapy and XEOL effects simultaneously, and the latter further

Accepted Manuscript
activates the PDT process of RB. Western blot analysis further confirmed that X-PDT
using AIE-Au nanosensitizers induced significant levels of lipid oxidation and DNA
damage as shown by the expression of COX-2 and γH2AX (Figure 2g).
The surviving fraction of U87MG cells was evaluated by a clonogenic assay. As shown
in Figure 2h, both enhanced AIE-GCs-mediated RT (termed as ERT) and X-PDT
induced excellent radiosensitization with radiation enhancement factors at the dose
required for 10% survival (* P < 0.05, *** P < 0.001).[18] The X-PDT contribution was
confirmed by fitting the dose-response curves with the function: 𝐹(𝐷) = 𝑒𝑥𝑝( −
𝛼 𝐷 − 𝛽𝐷 ), where D is the radiation dose and F(D) is the survival fraction. The α/β
value indicated the extent of the early radiation response (ERT, 1.70; X-PDT, 2.83). At
the same Au concentration, X-PDT displayed more efficient radiosensitization, which
generated free radicals from RT and 1O2 from PDT at the same time.[7d]
Since we observed efficient cellular uptake and killing of R-AIE-Au by X-PDT, the
accumulation of R-AIE-Au in U87MG tumors was then investigated. Both fluorescence
and CT imaging were conducted in tumor-bearing mice after tail vein injection of R-
AIE-Au (20 mg/kg) at 0, 2, 4, 8, 12 and 24 h post-injection. The phantom study revealed
that AIE-Au showed strong CT signals, due to the existence of Au and I atoms (Figure
S9), and strong fluorescence signals of RB (Figure S8). Strong fluorescence (Ex/Em:
570/585 nm) (Figures 3a, b) and CT signals (Figures 3c, d) were found in the tumor
region (red circles) and the intensity increased over time, reaching a plateau at 24 h
post-injection, which suggested effective accumulation in the tumors. The
biodistribution and clearance behaviors of R-AIE-Au on U87MG tumor-bearing mice
indicated that AIE-Au had a relatively long circulation half-life (3.7 ± 0.4 h) (Figure

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Angewandte Chemie International Edition 10.1002/anie.201908712

3e), which resulted in the accumulation of AIE-Au in U87MG tumors at levels as high
as 16.7 ± 1.2% injected dose per gram tissue (%ID/g), as well as a low
reticuloendothelial system uptake (tumor-to-liver, 1.0 ± 0.2; tumor-to-spleen, 1.0 ± 0.1)
(Figure 3f).
Encouraged by the efficient cellular killing rate of the low-dosage of X-PDT in vitro
and high tumor uptake in vivo, we then evaluated in vivo anticancer efficacies in

Accepted Manuscript
U87MG tumor-bearing mice after tail vein injection of R-AIE-Au (20 mg/kg). When
the tumors reached approximately 80 mm3 in volume, the mice were randomly divided
into five groups (n = 5/group), and the treatments were scheduled as shown in Figure
4a. Both R-AIE-GCs and R-AIE-Au resulted in tumor regression at low X-ray doses (1
Gy). More impressively, the R-AIE-Au treatment achieved rapid tumor regression at
the end, and the tumor inhibition rate was 97.1% (P < 0.001) (Figures 4b, c), compared
with the tumor inhibition rate of the R-AIE-GCs treatment (32.7%, P < 0.05). The
photographs of the mice on days 0, 6, and 15 also exhibited consistent results with the
tumor growth (Figure 4d). The size of the tumors in the R-AIE-Au treatment group
was significantly smaller than that of the other groups. H&E histological staining
indicated that tumors in the R-AIE-Au treatment group had serious destruction of the
architecture of the tumor tissue (Figure 4e). All of the treatments showed minimal
toxicity, as evidenced by the stable body weights (Figure 4f), lack of histopathological
changes in major organs (Figure S15), and normal results for serum and blood panel
analysis (Figures S16, S17).
Moreover, we evaluated the in vitro and in vivo anticancer efficacies of R-AIE-Au
nanosensitizers in other radioresistant cancer models, including hepatocellular
carcinoma (HepG2) and prostate cancer (PC3) cell lines. MTT (Figures 5a, 5b) and
clonogenic assays (Figures 5c, 5d) of both HepG2 and PC3 cells showed significant
destruction in the short-term survival and proliferation abilities with X-PDT treatment.
The in vivo therapy of subcutaneous HepG2 and PC3 tumors Showed X-PDT treatment
(1 Gy) resulted in rapid tumor regression at extremely low X-ray doses with minor
toxicity (Figures 5e, 5f, S18) than that of RT group with a high dose of irradiation (5

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Angewandte Chemie International Edition 10.1002/anie.201908712

Gy) (Figures 5e, 5f, S19).

In summary, we designed an aggregation-induced emission heterogeneous
photosensitizer-conjugated gold clustoluminogen (AIE-Au) for efficient low-dose X-
ray induced photodynamic therapy (X-PDT). The integration of glutathione-protected
GCs into heterogeneous clustoluminogen led to aggregation-induced emission. Under
a low-dose of X-ray irradiation, Au atoms not only strongly absorbed X-rays and

Accepted Manuscript
efficiently generated hydroxyl radicals, resulting in an enhanced RT effect, but also
converted X-rays to optical luminescence, exciting the conjugated photosensitizers for
PDT. X-ray-triggered ROS generation by the AIE-Au enabled a highly effective
treatment for radioresistant cancers via the unique X-PDT mechanism, with an order-
of-magnitude reduction in the X-ray dose. Thus, AIE-Au has the potential for the
treatment of deep-penetrating cancer.

Supporting information and the ORCID identification number(s) for the author(s) of
this article can be found under:
https://doi.org/xxx.

Conflict of interest
The authors declare no conflict of interest.

Acknowledgements
The work was supported by the National Key Research and Development Program of
China (2018YFA0107301), the National Science Foundation of China (81771977), the
Fundamental Research Funds for the Central Universities of China (20720180054), and
the Intramural Research Program (IRP), National Institute of Biomedical Imaging and
Bioengineering (NIBIB), National Institutes of Health (NIH). All animal experiments
were approved by the Animal Management and Ethics Committee of the Xiamen
University. We thank LetPub (www.letpub.com) for its linguistic assistance during the
preparation of this manuscript.

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Accepted Manuscript
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Accepted Manuscript
Scheme 1. Schematic diagrams of gold nanosensitizers-mediated X-ray-induced
therapy for radioresistant tumors: (a, b) Schematic illustrations showing the preparation
of AIE-GCs (a) and R-AIE-Au (b) nanosensitizers. (c) A working model of R-AIE-Au
for fluorescence and CT imaging-guided X-ray-induced enhanced RT and PDT.

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Angewandte Chemie International Edition 10.1002/anie.201908712

Accepted Manuscript
Figure 1. Synthesis and characterization of AIE-GCs and AIE-Au nanosensitizers. (a,
b) TEM images of GCs (a) and AIE-GCs (b). (c) STEM elemental mapping of AIE-
GCs. (d) The luminescence spectra of GCs (black line) and AIE-GCs (red line)
activated by X-ray irradiation (50 kV, 70 μA). (e, f) TEM images of RB-GCs (e) and
AIE-Au (f). (g) STEM elemental mapping of AIE-Au. (h) TEM images of R-AIE-Au.

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Accepted Manuscript
Figure 2. Mechanism studies on the U87MG cell killing efficacy: (a) The absorption
spectra of ABDA in different solutions with or without X-ray irradiation (50 kV, 70 μA).
(b) The viability of U87MG cells treated with different concentrations of R-AIE-Au
with or without X-ray irradiation (1 Gy). (c) Fluorescent images of U87MG cells
stained by SOSG after different treatments. Green fluorescence indicated the presence
of 1O2. (d) Fluorescent images of calcein-AM (green fluorescence for live cells) and PI
(red fluorescence for dead cells) co-stained U87MG cells exposed to different
treatments. (e) Lipid damage assessment measured by lipid peroxidation assays. (f)
DNA damage (dashed circle) was assessed by single cell electrophoresis assays. (g)
Western blot analysis confirmed the impact of X-PDT on DNA and membrane lipids.
(h) Cell reproductive capacity as measured by clonogenic assays taken 10 days after
different treatments (RT, ERT, and X-PDT).

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Angewandte Chemie International Edition 10.1002/anie.201908712

Accepted Manuscript
Figure 3. The in vivo imaging and metabolism assays with intravenously injected R-
AIE-Au nanosensitizers: (a, b) The in vivo fluorescent images of tumor-bearing mice
(a) and the corresponding fluorescence intensity in tumors (b) at 2, 4, 8, 12, and 24
hours post-injection of R-AIE-Au. (c, d) The in vivo CT imaging of tumor-bearing mice
(c) and the corresponding CT signal in tumors (d) at 2, 4, 8, 12, and 24 hours post-
injection of R-AIE-Au. The red circles indicate the tumors. (e) Blood-circulation
lifetime of R-AIE-Au determined by ICP-MS analysis of gold elements after
intravenous injection into BALB/c mice (n = 3). The concentration in the blood was
normalized as the percentage of the injected dose per gram of blood (%ID/g). (f)
Biodistribution of R-AIE-Au in tissues and tumors after intravenous administration at
various time intervals (1, 2, 4, 8, 12, 24, and 48 hours) (n = 3). The R-AIE-Au
concentrations were normalized as the percentage of the injected dose of gold element
per gram of each organ (%ID/g).

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Angewandte Chemie International Edition 10.1002/anie.201908712

Accepted Manuscript
Figure 4. The in vivo evaluation of X-PDT. (a) A schematic illustration of in vivo
antitumor treatment. (b) Tumor growth curves of different groups of tumor-bearing
mice after various treatments (***: P < 0.001, *: P < 0.05). (c) Images of representative
tumors taken from mice in different treatment groups. (d) Representative photographs
of mice bearing U87MG tumors that were treated on days 0, 6, and 15. (e) Hematoxylin
& eosin (H&E)-stained tumor sections from tumor-bearing mice after various
treatments (scale bar, 100 µm). (f) The change in body weight of mice bearing tumors
in different treatment groups.

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Angewandte Chemie International Edition 10.1002/anie.201908712

a 120
- X-rays + X-rays HepG2 b 120 - X-rays + X-rays PC3
100 100

Cell viability (%)

Cell viability (%)

***
***
80 80

60 60

40 40

20 20

0 0
0 50 100 200 400 0 50 100 200 400
R-AIE-Au (μg/mL) R-AIE-Au (μg/mL)

Accepted Manuscript
c HepG2
d PC3
100 100
Survival fraction (%)

Survival fraction (%)

***
***
10 10
PBS+X-ray PBS+X-ray
R-AIE-Au+X-ray R-AIE-Au+X-ray

1 1
0 2 4 6 8 0 2 4 6 8
Dose (Gy) Dose (Gy)
e 6
HepG2
f PC3
PBS+5 Gy X-rays PBS+5 Gy X-rays
Relative tumor volume (V/V0)

8
Relative tumor volume (V/V0)

R-AIE-Au+1 Gy X-rays R-AIE-Au+1 Gy X-rays

4 6

***
***

2
2

0 0
0 3 6 9 12 15 0 3 6 9 12 15
Time (days) Time (days)

Figure 5. The in vitro and in vivo anticancer efficacies of R-AIE-Au nanosensitizers in

radioresistant hepatocellular carcinoma (HepG2) and prostate cancer (PC3) cells: (a, b)
Viability of HepG2 (a) and PC3 (b) cells treated with different concentrations of R-
AIE-Au with or without X-ray irradiation (1 Gy). (c, d) Cellular reproductive capacity
of HepG2 (c) and PC3 (d) cells as measured by clonogenic assays performed 10 days
after RT (X-ray) or X-PDT (R-AIE-Au + X-ray). (e, f) Tumor growth curves of HepG2
(e) and PC3 (f) tumor-bearing mice after different treatments.

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Angewandte Chemie International Edition 10.1002/anie.201908712

TOC

Accepted Manuscript

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