Polymerization-Enhanced Photosensitization

Article abstract of DOI:10.1016/j.chempr.2018.06.003

Effective photosensitizers are highly desirable in many applications, such as photodynamic therapy, photocatalytic organic waste decomposition, and synthetic chemistry. Herein, we demonstrate polymerization-enhanced photosensitization, in which conjugated-polymer-based photosensitizers show much higher efficiency in singlet oxygen (¹O₂) production than their small-molecule analogs. Based on small-molecule photosensitizers SM1–SM4 with long wavelength emission, four conjugated polymer photosensitizers, CP1–CP4, were prepared. Interestingly, the conjugated polymer photosensitizers CP1–CP4 showed 5.06-, 5.07-, 1.73-, and 3.42-fold higher ¹O₂ generation efficiency than SM1–SM4, respectively. The improved intersystem crossing process from the singlet excitation states to the triplet excitation states and improved light-harvesting ability are essential to the enhancement of ¹O₂ generation efficiency. To illustrate the advantages of conjugated polymer photosensitizers on various applications, we demonstrate the superior performance of CP1 by using photoinduced organic waste decomposition, photoinduced organic oxidation reaction, and photodynamic cancer therapy as examples. Organic photosensitizers (PSs) are unique compounds that can absorb light or electromagnetic waves and transform them into reactive molecules, such as singlet oxygen (¹O₂). Highly efficient PSs are in great demand for many applications, such as photodynamic therapy, photoinduced organic waste decomposition, and photocatalytic organic synthesis. In this work, we propose the concept of polymerization-enhanced photosensitization. We show that polymerization of small-molecule PSs into conjugated polymers could significantly enhance their efficiency in ¹O₂ production with superior performance to that of commercial PSs (e.g., Ce6) in various applications. This concept is anticipated to open up new opportunities for rational photosensitizer design and applications. Effective photosensitizers are highly desirable in many applications. Herein, Liu and co-workers demonstrate polymerization-enhanced photosensitization, in which conjugated-polymer-based photosensitizers show much higher efficiency in singlet oxygen (¹O₂) production than their small-molecule analogs. Based on this concept, conjugated polymer photosensitizer CP1 with an aggregation-induced emission feature is proposed to show highly efficient ¹O₂ generation ability superior to that of its small-molecule analog SM1 and commercial photosensitizer Ce6 in photodynamic therapy, organic waste decomposition, and photocatalytic reactions.

Full text of DOI:10.1016/j.chempr.2018.06.003

Article
Polymerization-Enhanced Photosensitization
Wenbo Wu, Duo Mao, Shidang
Xu, ..., Xueqi Li, Deling Kong,
Bin Liu
cheliub@nus.edu.sg
HIGHLIGHTS
The concept of ‘‘polymerization-
enhanced photosensitization’’ is
proposed
Highly efficient AIE-conjugated
polymer photosensitizers are
synthesized
Conjugated polymer (CP)
photosensitizers offer highly
efficient photodynamic therapy
CP photosensitizers are effective
in organic waste decomposition
and organic synthesis
Effective photosensitizers are highly desirable in many applications. Herein, Liu
and co-workers demonstrate polymerization-enhanced photosensitization, in
which conjugated-polymer-based photosensitizers show much higher efficiency in
singlet oxygen (1O2) production than their small-molecule analogs. Based on this
concept, conjugated polymer photosensitizer CP1 with an aggregation-induced
emission feature is proposed to show highly efficient 1O2 generation ability
superior to that of its small-molecule analog SM1 and commercial photosensitizer
Ce6 in photodynamic therapy, organic waste decomposition, and photocatalytic
reactions.
Wu et al., Chem 4, 1–15
August 9, 2018 ª 2018 Elsevier Inc.
https://doi.org/10.1016/j.chempr.2018.06.003

Please cite this article in press as: Wu et al., Polymerization-Enhanced Photosensitization, Chem (2018), https://doi.org/10.1016/
j.chempr.2018.06.003
Article
Polymerization-Enhanced Photosensitization
Wenbo Wu,1,2,5 Duo Mao,1,5 Shidang Xu,1 Kenry,1 Fang Hu,1 Xueqi Li,1 Deling Kong,3 and Bin Liu1,4,6,
*
SUMMARY
The Bigger Picture
Organic photosensitizers (PSs) are
unique compounds that can
absorb light or electromagnetic
waves and transform them into
reactive molecules, such as singlet
oxygen (1O2). Highly efficient PSs
are in great demand for many
applications, such as
Effective photosensitizers are highly desirable in many applications, such as
photodynamic therapy, photocatalytic organic waste decomposition, and syn-
thetic chemistry. Herein, we demonstrate polymerization-enhanced photosen-
sitization, in which conjugated-polymer-based photosensitizers show much
higher efficiency in singlet oxygen (1O2) production than their small-molecule
analogs. Based on small-molecule photosensitizers SM1–SM4 with long wave-
length emission, four conjugated polymer photosensitizers, CP1–CP4, were
prepared. Interestingly, the conjugated polymer photosensitizers CP1–CP4
showed 5.06-, 5.07-, 1.73-, and 3.42-fold higher 1O2 generation efficiency
than SM1–SM4, respectively. The improved intersystem crossing process from
the singlet excitation states to the triplet excitation states and improved
light-harvesting ability are essential to the enhancement of 1O2 generation
efficiency. To illustrate the advantages of conjugated polymer photosensitizers
on various applications, we demonstrate the superior performance of CP1 by
using photoinduced organic waste decomposition, photoinduced organic
oxidation reaction, and photodynamic cancer therapy as examples.
photodynamic therapy,
photoinduced organic waste
decomposition, and
photocatalytic organic synthesis.
In this work, we propose the
concept of polymerization-
enhanced photosensitization. We
show that polymerization of small-
molecule PSs into conjugated
polymers could significantly
enhance their efficiency in 1O2
production with superior
INTRODUCTION
Photosensitized singlet oxygen (1O2) has attracted tremendous research interest
because of its potential applications in numerous fields.1–9 In a typical photosensitiza-
tion process (Figure 1A), the photosensitizer molecule is excited under light irradiation.
The excited electrons then migrate to the lowest triplet excited state (T1) from the
lowest singlet excited state (S1) through a specific process known as intersystem
crossing (ISC). Subsequently, the interactions between T1 of PS and ground-state O2
(3O2) can induce the generation of 1O2, which is one of the main relaxation mechanisms
from T1 to ground state of photosensitizers. 1O2 is generally unstable and possesses a
strong oxidizing property, which can kill surrounding cancer or bacterial cells to realize
photodynamic therapy (PDT),1–5 destroy organic waste to realize wastewater treat-
ment,6 and oxidize some reactants to yield new organic compounds.7,8 For many prac-
tical applications, such as PDT and wastewater treatment, photosensitizers are usually
used in aqueous phase. Under such conditions, hydrophobic organic photosensitizers
tend to aggregate and result in aggregation-caused fluorescence quenching with
reduced 1O2 production.10,11 To address this issue, we developed photosensitizers
with aggregation-induced emission (AIE).12,13 AIE is a unique phenomenon for
fluorophores containing rotor structures, which show enhanced fluorescence in the
aggregate state compared with in solution because the restriction of intramolecular
motion can severely suppress the non-radiative transition of AIE photosensitizers in
the aggregate state.14 It has also been confirmed that AIE photosensitizers are able
to offer effective 1O2 production in the aggregate nanoparticle format.15,16 Therefore,
modification on AIE photosensitizers has great potential to offer further improved
photosensitization performance because of their quenched non-radiative decay in
the aggregate state. To date, AIE photosensitizers have been widely employed in
image-guided cancer cell and bacteria ablation.17–23
performance to that of
commercial PSs (e.g., Ce6) in
various applications. This concept
is anticipated to open up new
opportunities for rational
photosensitizer design and
applications.
Chem 4, 1–15, August 9, 2018 ª 2018 Elsevier Inc.
1

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Figure 1. Working Mechanism of Photosensitizers and the Design Principle of This Work
The different photosensitization processes of small-molecule photosensitizer (A) and conjugated
polymer photosensitizer (B).
From the photosensitization process shown in Figure 1A, it is well understood that
the 1O2 generation efficiency, which is one of the most important parameters of
PSs, can be controlled by manipulation of the ISC process, and several methods
have been used to enhance the ISC process for better performance of photosensi-
tizers. Introducing heavy atoms serves as one of the most effective strategies
for controlling the ISC process because it can enhance spin-orbit coupling of photo-
sensitizers.9,24 However, heavy atoms often induce dark toxicity, making them
unsuitable for PDT applications.24–26 Recently, we confirmed that reducing DES1-T1
(the energy gap between S1 and T1) is advantageous in promoting the ISC pro-
cess.27–29 This was achieved through separation between the highest-energy occu-
pied molecular orbital (HOMO) and the lowest-energy unoccupied molecular orbital
(LUMO), which yielded photosensitizers with limited conjugation and poor visible-
light absorption, rendering them less suitable for highly effective photosensitiza-
tion.28,29 Although our recent design of D-A-p-A type photosensitizers can partially
fix this problem,29 this strategy requires very precise molecular design. As such, it
remains challenging to achieve significant improvement in the performance of
organic photosensitizers.
Conjugated polymers are macromolecules with backbones containing p-conju-
1Department of Chemical and Biomolecular
Engineering, National University of Singapore, 4
Engineering Drive 4, Singapore 117585,
Singapore
gated structural units. This configuration endows them with a strong light-harvesting
ability in comparison with that of their small-molecule analogs.30–32 For example,
with the extension of the conjugation length, the absorption peaks of fully
conjugated polyporphyrin are significantly red-shifted with enhanced absorbance.33
With the improved light-harvesting ability, conjugated polymers have been used
as energy donors to improve the photosensitization via energy transfer from conju-
gated polymers to the photosensitizer acceptors.31,34,35 In addition, compared with
traditional small-molecule photosensitizers, conjugated polymers possess many
energy levels in each energy band (Figure 1B).36 This feature offers two major
advantages. First, as shown in Figure 1B, the relatively broad energy bands can
reduce the overall DES-T value, which is helpful for 1O2 production.27–29 Second,
besides the original ISC process from S1 to T1, some other ISC processes from singlet
states to different triplet states are also possible because of their similar energy
levels (Figure 1B).36,37 Therefore, once small molecules are polymerized into conju-
gated polymers, they can serve as more effective photosensitizers with enhanced
photosensitizing performance.
2Department of Materials Science and
Engineering, National University of Singapore, 7
Engineering Drive 1, Singapore 117574,
Singapore
3State Key Laboratory of Medicinal Chemical
Biology, Key Laboratory of Bioactive Materials,
Ministry of Education and College of Life
Sciences, Nankai University, Tianjin 300071, China
4Institute of Materials Research and Engineering,
Innovis, 2 Fusionopolis Way, Singapore 138634,
Singapore
5These authors contribute equally
6Lead Contact
*Correspondence: cheliub@nus.edu.sg
https://doi.org/10.1016/j.chempr.2018.06.003
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Figure 2. The Molecules Investigated in This Work
The chemical structures of small molecules SM1–SM4 and conjugated polymers CP1–CP4.
In this contribution, we propose a method to improve the photosensitization effi-
ciency of organic photosensitizers. Based on three reported AIE photosensitizers
SM1–SM3 and a non-AIE compound of SM4, four conjugated polymer photosensi-
tizers, CP1–CP4 (Figure 2), were prepared. Compared with their small-molecule
counterparts, CP1–CP4 show much higher photosensitization efficiency attributable
to the improved ISC process and enhanced light-harvesting ability of conjugated
polymers, which is termed the ‘‘polymerization-enhanced photosensitization’’
effect in this work. Among these conjugated polymers, CP1 showed the highest
1O2 generation efficiency in aqueous media, which was 3.71-fold higher than
that of Ce6, the most widely used PS, under white-light irradiation (60 mW/cm2,
400–700 nm).38,39 Such a high 1O2 generation efficiency makes CP1 a good
candidate for practical applications, which we confirmed via in vitro and in vivo
photodynamic cancer cell ablation and tumor therapy, photoinduced organic waste
decomposition, and organic synthesis by photocatalytic oxidation reaction.
RESULTS AND DISCUSSION
Molecular Design and Optical Properties
SM128,29 and SM2 (Figure 2)16 are two reported photosensitizers with AIE character-
istics, whereas SM340 is a more established AIE fluorophore. Based on SM1–SM3,
CP1–CP3 (Figure 2), whose repeat units have structures very similar to those of
SM1–SM3, were designed and synthesized (their synthetic routes, nuclear magnetic
resonance spectra, and gel permeation chromatography chromatograms are shown
in Scheme S1 and Figures S1–S4, respectively) for the study of the structure-property
relationship between small-molecule photosensitizers and conjugated polymer
photosensitizers. In addition, SM441 and CP442 (Figure 2) without AIE characteristics
were also synthesized for demonstrating the generality of polymerization-enhanced
photosensitization. All of the conjugated polymers had molecular weights in the
range of 9,500–19,500 g/mol (Table 1).
SM1 (Figure 2), with methoxy-substituted tetraphenylethylene as the electron donor
and dicyanovinyl as the electron acceptor, had absorption and emission maxima
at 410 and 620 nm, respectively, in a tetrahydrofuran (THF)/water (1/99, v/v)
solution (Figures 3A and 3B). Because of the increased conjugation length, CP1
(Mw = 17,000, Mw/Mn = 1.45) showed better absorption than SM1 in the visible range
(Figure 3A), indicating stronger light-harvesting ability of CP1. Inheriting from SM1,
CP1 also exhibited the AIE feature. As shown in Figure 3B, CP1 was non-emissive in
THF solution, whereas its emission with a maximum at around 640 nm was observed
along with the addition of water, a poor solvent of CP1. In THF/water (1/99, v/v), the
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Table 1. Comparison between Conjugated Polymer Photosensitizers and Small-Molecule
Photosensitizers
No. Mwa (g$molꢀ1
)
Mw/Mn
(ꢀ)
lmaxb (nm)
c3 (L$molꢀ1$cmꢀ1
)
QYd (%) 1O2 Generation
Efficiencye (nmol)
a
SM1 (ꢀ)
318
420
335
335
435
340
435
315
485
320
485
335
460
380
520
2.59 3 104
1.16 3 104
5.50 3 104
3.02 3 104
9.01 3 103
3.60 3 104
1.02 3 104
2.28 3 104
1.11 3 104
4.00 3 104
1.47 3 104
2.26 3 104
1.36 3 104
1.92 3 104
2.24 3 104
12.1
4.02
CP1 17,000
SM2 (ꢀ)
1.45
6.2
1.2
20.3
(ꢀ)
0.27
1.37
2.5
CP2 19,500
SM3 (ꢀ)
1.66
(ꢀ)
ꢁ0
39.2
5.5
CP3 9,500
SM4 (ꢀ)
1.92
(ꢀ)
4.3
14.2
1.7
3.75
CP4 10,800
2.00
16.4
aDetermined by gel permeation chromatography in THF on the basis of polystyrene calibration.
bAbsorption peaks of photosensitizers in THF/water = 1/99 (v/v).
cMolar absorption coefficients of photosensitizers at the absorption peaks in THF/water = 1/99 (v/v).
dQuantum yield of photosensitizers in THF/water = 1/99 (v/v) with 4-(dicyanomethylene)-2-methyl-6-
(4-dimethylaminostyryl)-4H-pyran (43% in methanol) as reference.
eTested with ABDA as an indicator, the values are based on the consumed amount of ABDA by 10 nmol of
different photosensitizers upon white-light irradiation (60 mW/cm2, 400–700 nm) for 1 min.
quantum yield of CP1 was 6.2% (reference: 4-(dicyanomethylene)-2-methyl-6-
(4-dimethylaminostyryl)-4H-pyran, 43% in methanol), nearly half that of SM1
1
(12.1%). To evaluate the O2 generation efficiency of SM1 and CP1, we used 9,10-
anthracenediyl-bis(methylene)dimalonic acid (ABDA), a commercially available
1O2 indicator. As shown in Figures 3C and S5, both SM1 and CP1 gradually
decreased the absorbance of ABDA (50 mmol/L) in THF/water (1/99, v/v) mixture
under white-light irradiation (60 mW/cm2, 400–700 nm; Figure S6A). This indicates
that ABDA was degraded by the generated 1O2. From the degradation of ABDA,
the 1O2 generation efficiency was evaluated. Within 1 min, 4.02 and 20.3 nmol
(Table 1) of ABDA were degraded by 10 nmol of SM1 and CP1, respectively. Under
the same testing conditions, for 10 nmol of Ce6, only 5.47 nmol of ABDA was
degraded, which reveals the high efficiency of CP1 in 1O2 generation (Figure S7).
In addition, when NaN3, an 1O2 scavenger, was added to the tested system, the
absorbance of ABDA could not change with SM1 or CP1 under white-light irradia-
tion (60 mW/cm2, 400–700 nm; Figure 3C), which confirms that 1O2 was the main
component of generated reactive oxygen species by these photosensitizers under
light irradiation.
Similar phenomena were also observed in the SM2/CP2 and SM3/CP3 systems. As
shown in Figure S8 and Table 1, in THF/water (1/99, v/v), SM2 showed absorption
and emission maxima at 435 and 650 nm, respectively, and a quantum yield of
1.2%. SM2 (10 nmol) degraded 1.04 nmol ABDA within 1 min under light irradiation
(60 mW/cm2, 400–700 nm). The same light illumination condition was used for other
comparisons. After polymerization, CP2 (Mw = 19,500, Mw/Mn = 1.66) displayed an
4
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Figure 3. Optical and Photosensitization Properties of SM1 and CP1
(A) UV-vis spectra of SM1 and CP1 in THF/water = 1/99 (v/v).
(B) PL spectra (lex = 420 nm) of SM1 and CP1 in THF (dashed line) and THF/water = 1/99 (v/v) (solid line).
(C) Degradation rates of ABDA by SM1 and CP1 with or without NaN3 in THF/water = 1/99 (v/v); A0 and A are the absorbance of ABDA in the presence of
the photosensitizers at 378 nm before and after irradiation (60 mW/cm2, 400–700 nm), respectively. Conditions: [SM1] = 1 3 10ꢀ5 M, [CP1] = 1 3 10ꢀ5 M
based on repeat unit, [ABDA] = 5 3 10ꢀ5 M, [NaN3] = 10 mg/mL.
absorption peak similar to that of SM2 but with a slightly enhanced light absorption.
Compared with SM2, CP2 exhibited nearly no emission. However, it showed 5.07-
fold higher 1O2 generation in the THF/water (1/99, v/v) mixture. The lower photolu-
minescence (PL) intensity and decreased 1O2 generation efficiency of CP2 relative to
those of CP1 occurred because the acceptor in CP2 was much stronger than that in
CP1. The strong charge transfer character led to quenched fluorescence and
reduced 1O2 generation in polar media. Figure S9 and Table 1 illustrate the proper-
ties of SM3 and CP3 in THF/water (1/99, v/v). SM3 showed absorption and emission
peaks at 480 and 620 nm, respectively, and a fluorescence quantum yield of 39.2%.
CP3 (Mw = 9,500, Mw/Mn = 1.92) had absorption and emission maxima similar to
those of SM3, but its fluorescence quantum yield was significantly decreased to
5.5%. On the contrary, the 1O2 generation efficiency of CP3 was obviously improved.
In fact, CP3 (10 nmol) was able to degrade 4.3 nmol ABDA within 1 min under light
irradiation, which is nearly twice that for SM3.
To study whether polymerization-enhanced photosensitization can be applied to a
non-AIE system, we also tested the properties of SM4 and CP4, and the results
are shown in Figure S10 and Table 1. In THF/water (1/99, v/v), the absorption and
emission peaks of SM4 were centered at 460 and 615 nm, respectively. After poly-
merization, these peaks were red-shifted to 510 and 670 nm, respectively, indicating
better conjugation in CP4 (Mw = 10,800, Mw/Mn = 2.00). Similar to the previous ex-
amples, the fluorescence quantum yield of CP4 (1.7%) was significantly lower than
that for SM4 (14.2%). Within 1 min, 3.75 and 16.4 nmol of ABDA were degraded
by 10 nmol of SM4 and CP4 under white-light irradiation, respectively. Considering
obviously different light-harvesting abilities between SM4 and CP4, a blue LED with
a narrow emission peak centered at 450 nm (50 mW/cm2, spectrum shown in Fig-
ure S6B) was further employed as the light source to normalize light absorption.
At the same concentration, both SM4 and CP4 showed a similar absorbance at
450 nm (Figure S9A). As shown in Figures S10E and S10F, the 1O2 generation
efficiency of CP4 was still 3.42-fold higher than that of SM4, indicating that polymer-
ization-enhanced photosensitization is also effective in a non-AIE system, which
expanded the scope of the concept.
Mechanism of Polymerization-Enhanced Photosensitization Effect
Among these polymers, CP1 showed the highest PL intensity and the most effective
1O2 generation upon excitation, which was 3.71-fold higher than that of the most
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widely used photosensitizer Ce6. As such, the SM1/CP1 system was selected as the
model for further investigation of the polymerization-enhanced photosensitization.
Based on the chemical structures of SM1 and CP1, model compounds 1–4 (whose
chemical structures and optimized 3D structures are shown in Figures 4A and S11,
respectively) with different repeat units were proposed. Time-dependent density
functional theory (TD-DFT) investigations43,44 were then performed on these model
compounds 1–4 in both singlet and triplet excited states to probe the differences
between small molecules and conjugated polymers. As shown in Figure 4B, with
the increased number of repeat units, the energy of upper excited states (Sn and
Tn) decreased gradually and moved closer to the lowest excited states (S1 and T1).
The more repeat units, the denser the excited states. Therefore, it can be hypothe-
sized that further increasing the number of repeat units could eventually lead to
two band-like energy-level distributions emerging in singlet and triplet states. It is
noteworthy that the dense energy-level distributions are highly beneficial for the
ISC process to facilitate 1O2 production, which has been confirmed by the Kohn-
Sham frontier orbital analysis (Figure 4C). When n = 1, the calculated energy gap be-
tween S1 and T1 is 0.23 eV, which is smaller than 0.3 eV, facilitating the singlet-triplet
ISC process.44 In addition, the transitional configurations and iso-surfaces of S1 and
T3 are similar (Figures S12 and S13), rendering the spin-orbit coupling and the ISC
process from S1 to either T2 or T3 possible (Figure 3C and Table S1).45 These three
ISC transitions endow SM1 with a photosensitization capability. When n = 4, the
energy levels of T1–T7 are all lower than that of S1, and all energy gaps between
S1 and Tn (n = 1–7) are smaller than 0.3 eV (Figure 3C). In addition, according to
calculations, most ISC transitions from S1 to Tn (n = 1–12) are possible (Figures
S14 and S15 and Table S2). The significantly enhanced energy transition channels
from n = 1 to n = 4 should greatly facilitate the ISC process.46 When the repeat units
are further increased to form conjugated polymers, the energy transition channels
for ISC from singlet to triplet states should increase accordingly. As a consequence,
the 1O2 generation efficiency of conjugated polymers is expected to be higher than
that of their small-molecule analogs. Meanwhile, because of the much easier ISC
process from singlet to triplet states, the fluorescence quantum yield of conjugated
polymers is lower than that of small molecules.
Besides ISC process, the light-harvesting ability is also very important for 1O2 pro-
duction.27,29,34,35 Therefore, the oscillator strength of the model compounds was
also calculated by the TD-DFT method (Figure S16). In comparison with n = 1, the
oscillator strength in the visible range was obviously enhanced at n = 4, indicating
that the absorbance in the visible range of CP1 should be larger than that of SM1,
which is consistent with the experimental result. In fact, not only in the CM1/CP1
system but also in the other three systems, the molar absorption coefficients of
conjugated polymers were enhanced compared with those of their corresponding
small-molecule counterparts. As such, the improved light-harvesting ability could
enhance the photosensitization effect of conjugated polymers.
Photoinduced Organic Waste Decomposition
Photocatalysis organic waste decomposition is considered a promising option in
sewage purification for areas with insufficient infrastructure but high yearly sun-
shine.6 The typical photocatalytic technology is based on the interaction of light
with suspended photosensitizers to produce highly oxidative species to decompose
the waste.47–50 Considering the efficiency and stability, the most widely used photo-
sensitizers are inorganic materials47–50 or metal complexes.6 So far, pure organic/
polymeric photosensitizers have not been used in this area, since most of the
commercially available photosensitizers (e.g., Ce6, methylene blue, Rose bengal,
6
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Figure 4. Modeling Analysis by TD-DFT
(A) Chemical structures of the model compounds.
(B) Singlet and triplet energy levels of different model compounds.
(C) Calculated energy levels and possible ISC channels of different model compounds. S, T, H, and L stand for singlet, triplet, HOMO, and LUMO,
respectively. The plain and dashed arrows refer to the major and minor ISC channels, respectively.
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Figure 5. Behavior of CP1 and SM1 in Photoinduced Organic Waste Decomposition
(A) UV-vis spectra of Cy7 in the presence of CP1 under light irradiation (60 mW/cm2, 400–700 nm) for different times in water.
(B) Degradation rates of Cy7 by CP1, SM1, and Ce6; A0 and A are the absorbance of Cy7 in the presence of different photosensitizers at 780 nm before
and after irradiation (60 mW/cm2, 400–700 nm), respectively.
(C) Images of Cy7 solutions with different treatments: (a) in darkness; (b) under light irradiation for 2 min; (c) with SM1 under light irradiation for 2 min; (d)
with CP1 under light irradiation for 2 min.
(D) UV-vis spectra of Rhodamine 6G in the presence of CP1 under light irradiation (60 mW/cm2, 400–700 nm) for different times in water.
(E) Degradation rates of Rhodamine 6G by CP1, SM1, and Ce6; A0 and A are the absorbance of Rhodamine 6G in the presence of different
photosensitizers at 530 nm before and after irradiation (60 mW/cm2, 400–700 nm), respectively.
(F) Images of Rhodamine 6G solutions with different treatments: (a) in darkness, (b) under light irradiation for 2 hr, (c) with SM1 under light
irradiation for 2 hr, (d) with CP1 under light irradiation for 2 hr. Conditions: [SM1] = 1 3 10ꢀ5 M, [CP1] = 1 3 10ꢀ5 M based on repeat unit, [Cy7 or
Rhodamine 6G] = 1 3 10ꢀ4 M.
indocyanine green) are not stable under light irradiation (Figure S17), owing to their
reactions with the generated 1O2. Herein CP1, with excellent photostability (Fig-
ure S17), was used in organic waste decomposition for the first time. Under light irra-
diation, the generated 1O2 was expected to oxidize and dispose the waste. Here,
Cy7 and Rhodamine 6G were used as the organic waste samples for examination
of the photoinduced organic waste decomposition ability of CP1. In the presence
of CP1 (1 3 10ꢀ5 M based on repeat unit), Cy7 (1 3 10ꢀ4 M) could be totally decom-
posed under light irradiation (60 mW/cm2, 400–700 nm) within 2 min (Figure 5A). As
a reference, only 43%, and 53% of Cy7 could be decomposed by SM1 and Ce6 under
the same conditions (Figure 5B), respectively. Figure 5C shows the images of Cy7
solutions subjected to different treatments. It is obvious that in the presence of
CP1 after 2 min light irradiation, the solution became colorless and transparent in
comparison with other control groups.
In contrast to Cy7, Rhodamine 6G is much more stable. Therefore, a longer time was
needed (120 min) for its decomposition (1 3 10ꢀ4 M) by CP1 (1 3 10ꢀ5 M based on
repeat unit) under light irradiation (Figure 5D). As shown in Figures 5E and 5F,
without photosensitizers Rhodamine 6G was very stable under light irradiation
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Figure 6. Behavior of CP1 and Other Photosensitizers in Photoinduced Oxidation Reaction
(A) Conversion of benzaldehyde oxidation reaction with different photosensitizers as the catalysts
under irradiation (150 mW/cm2, 400–700 nm). The experiments were repeated three times, and the
error bars indicate the standard deviation of the three experiments.
(B) Results of different reactions with CP1 as the photosensitizer.
Reaction conditions: benzaldehyde, 1.06 g, 10 mmol; photosensitizers, 1 mmol. The conversion
efficiency was measured by high-performance liquid chromatography.
(60 mW/cm2, 400–700 nm), whereas with SM1 (1 3 10ꢀ5 M) or Ce6 (1 3 10ꢀ5 M), only
19% or 16% of Rhodamine 6G (1 3 10ꢀ4 M) was decomposed after 2 hr of light irra-
diation. The good performance of CP1 in decomposing organic waste by white light
promoted us to further investigate its behavior under sunshine. As shown in Fig-
ure S18, under sunshine for 2 hr most of the Rhodamine 6G (1 3 10ꢀ4 M) was decom-
posed by CP1 (1 3 10ꢀ5 M based on repeat unit), indicating the potential of CP1 in
decomposing organic waste. In addition, as CP1 is insoluble in water, it can be easily
removed by filtration after organic waste treatment (Figure S18).
Photoinduced Organic Synthesis by Oxidation Reaction
As the oxidizing property of 1O2 is much stronger than that of oxygen, in principle it
can oxidize some relatively stable compounds to yield new products.51,52 Effective
photosensitizers could be considered as catalysts for the realization of organic
synthesis under light irradiation. At present, this type of photoinduced oxidation
reaction has been applied to several reactions, such as bromination reaction,53
oxidative Ugi-type reaction,54 alcohol oxidation,55 and aldehyde oxidation.56
Because oxygen is a sustainable and clean oxidant, this type of reaction is very
promising in organic synthesis. The key for high reaction efficiency is the availability
of stable and highly effective photosensitizers, and the most common ones are
based on inorganic materials,55 microporous polymers,53 and metal complexes.54,56
In this study, we used the oxidation reaction of benzaldehyde to benzoic acid as an
example to demonstrate the applicability of CP1 for photoinduced organic synthe-
sis. After light irradiation (150 mW/cm2, 400–700 nm) for 4 hr, it is obvious that the
liquid benzaldehyde was converted to benzoic acid, a white solid, in the presence of
CP1 (Figure S19). Figure 6A shows the quantitative analysis results. With CP1 as the
photocatalyst, most of the benzaldehyde could be oxidized to benzoic acid under
light irradiation (150 mW/cm2, 400–700 nm) for 4 hr with a conversion rate of
78.3%. Under the same reaction conditions, the conversion rates were only 40.8%,
24.9%, and 20.6% with SM1, Rose bengal, and Ce6 as the photocatalysts, respec-
tively. Besides its effective 1O2 production, the good stability of CP1 also plays a
key role in its effective catalytic activity. As shown in Figure 6A, within 1 hr, a conver-
sion rate of 10% was achieved with Ce6 as the photosensitizer. However, this value
was only improved to 20.6% after 4 hr of light irradiation, given that Ce6 is unstable
under the same light irradiation condition (Figure S17). On the contrary, CP1 could
continuously generate 1O2 to oxidize the reactant. This result compares favorably
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with a literature report56 wherein a much longer time of 72 hr was required by using a
metal complex as the photocatalyst to yield 84% conversion of benzaldehyde to
benzoic acid. Additionally, we also tested two other substrates with ꢀF as the elec-
tron-withdrawing group or with ꢀOCH3 as the electron-donating group to demon-
strate the applicability of CP1 as the photocatalyst for oxidation (Figure 6B). Detailed
analysis revealed that both reagents could be oxidized with CP1 as the photocata-
lyst, and 4-fluorobenzaldehyde with electron-withdrawing group showed a higher
conversion rate of 84.2%.
Photoinduced Cancer Cell Ablation and Tumor Therapy
Given its good 1O2 generation efficiency and fluorescence quantum yield, CP1 was
selected for further PDT application with SM1 and Ce6 as the reference. As shown in
Figure 7A, to endow these hydrophobic photosensitizers with water dispersibility,
we encapsulated them within the DSPE-PEG2000 polymer matrix by a co-precipita-
tion method to generate nanoparticles (NPs). These NPs showed uniform sizes of
40–50 nm (Figure S20). The polyethylene glycol (PEG) chains of these NPs extend
into the aqueous medium to ensure their good water dispersibility, whereas the
hydrophobic photosensitizers are aggregated in the core.57 The AIE feature of
CP1 and SM1 enabled the NPs to show bright emission and effective 1O2 generation
(Figure S21A). As expected, CP1 NPs also showed much more effective 1O2 gener-
ation than SM1 NPs and Ce6 NPs. We further measured the 1O2 generation
efficiency of CP1 NPs in PBS buffer with different pH. As shown in Figure S21B,
CP1 NPs could still effectively generate 1O2 under physiological conditions
upon white-light irradiation, and in weak acid condition (pH = 5.6), which is the tumor
environment, its 1O2 generation was slightly more effective. This is very beneficial for
photodynamic anticancer therapy.
We chose 4T1 breast cancer cells to assess the image-guided PDT effect of CP1 NPs at
the cellular level. First, different photosensitizer NPs and 40,6-diamidino-2-phenylindole
(DAPI) were incubated with 4T1 cells for 12 hr, and the fluorescent signals were moni-
tored with a laser confocal fluorescence microscope. The obvious red fluorescence as
observed from the confocal images (Figure 7B) confirmed that CP1 NPs have good
imaging functionality similar to that of SM1 NPs and Ce6 NPs. Second, dichlorofluores-
cein diacetate (DCFDA, a reactive oxygen species indicator) was incubated with the
NP-labeled 4T1 cancer cells for 30 min. After 30 s of light irradiation, the cells showed
bright-green emission of DCFDA (Figures 7C and S22), verifying the 1O2 production of
NPs. Furthermore, given the emission brightness, it was evident that the 1O2 generation
efficiency of CP1 NPs in cancer cells was much higher than that of SM1 NPs and Ce6 NPs.
Thissuggeststhe better photodynamic efficacy of CP1 NPs, which was also confirmed by
the live- and dead-cell staining experiments, wherebylive and dead cells were stained by
fluorescein diacetate (green fluorescence) and propidium iodide (red fluorescence),
respectively. In the control group, only bright-green fluorescence was observed (Fig-
ure S23). However, under light irradiation (60 mW/cm2, 400–700 nm) for 5 min, the pop-
ulation of dead cells, as indicated by red fluorescence, increased at the expense of live
green emissive cells (Figure 7D). According to the proportion of cells with red and green
fluorescence, the PDT efficacy of CP1 NPs is much better than that of SM1 NPs and Ce6
NPs, which is consistent with their 1O2 generation efficiency. Quantitative evaluation re-
sults, measured by methylthiazolyldiphenyltetrazolium bromide (MTT) assay, are pre-
sented in Figures 4E–4G and S24. After incubating 4T1 cells with 100 mg/mL of CP1
NPs (based on CP1) for 12 hr, the cell viability was higher than 95%, indicating extremely
low toxicity of CP1 NPs. However, CP1 NPs were able to induce cytotoxicity to 4T1 cells
under only 5 min of light irradiation (60 mW/cm2) with a half-maximal inhibitory concen-
tration(IC50) of0.9 mg/mL, which ismuchlower thanthatof SM1 NPs (2.1 mg/mL) and Ce6
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Figure 7. Image-Guided PDT Results of CP1, SM1, and Ce6 NPs at Cellular Level
(A) Preparation of CP1 NPs.
(B) Confocal images of 4T1 breast cancer cells after incubation with different NPs (5 mg/mL based on molecule) for 12 hr. The red fluorescence of CP1 or
SM1 NPs was collected above 560 nm upon excitation at 405 nm, the red fluorescence of Ce6 NPs was collected above 650 nm upon excitation at
620 nm, and the blue fluorescence of DAPI was collected between 420 and 450 nm upon excitation at 405 nm. In all images, scale bars represent 50 mm.
(C) Detection of generated 1O2 in different NP-labeled 4T1 cancer cells (NP concentration = 5 mg/mL based on molecule) by dichlorofluorescein
diacetate (DCFDA, excitation: 488 nm, collection: 505–525 nm), followed by 2 min light irradiation (60 mW/cm2, 400–700 nm). In all images, scale bars
represent 50 mm.
(D) Live and dead staining of different NP-treated 4T1 cancer cells (NP concentration = 5 mg/mL based on molecule) after 5 min light irradiation (60 mW/cm2,
400–700 nm). The live cells were stained with fluorescein diacetate (green, 50 mg/mL for 10 min), whereas the dead cells were stained with propidium iodide (red,
100 mg/mL for 10 min). In all images, scale bars represent 50 mm.
(E–G) The viability of different NP-treated 4T1 cancer cells in darkness (E), under 60 mW/cm2 light irradiation for 5 min (F), or under 30 mW/cm2 light
irradiation for 10 min (G) was were tested by MTT assay. The experiments were repeated three times, and the error bars indicate the standard deviation
of the three experiments. *p < 0.05, **p < 0.01, one-way ANOVA.
NPs(1.3 mg/mL). Inaddition, evenunderalowerirradiationpowerdensityof30mW/cm2,
CP1 NPs could kill 4T1 cancer cells effectively with an IC50 value of 1.4 mg/mL, demon-
strating effective 1O2 generation ability of CP1 NPs.
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Figure 8. Behavior of CP1, SM1, and Ce6 NPs in In Vivo Image-Guided PDT
(A) Time-dependent in vivo fluorescent images of 4T1 tumor-bearing mouse after i.v. injection with
CP1 NPs (1 mg/mL based on CP1, 100 mL per mouse).
(B) Average fluorescence intensity of mice tumors over time after the mice were injected i.v. with
CP1 NPs (1 mg/mL based on CP1, 100 mL per mouse). Error bars indicate SEM.
(C) Tumor volume measurement of different groups of mice (NP dosage: 1 mg/mL based on molecule,
100 mL per mouse). Error bars indicate SEM (***p < 0.001, n = 5 per group, PDT of CP1 NPs versus control
groups; **p < 0.01, n = 5 per group, PDT of CP1 NPs versus PDT of SM1 or Ce6 NPs).
(D and E) H&E staining (D) and TUNEL immunostaining (E) of the tumor sections of mice after
14 days of treatment. The green fluorescence indicates the TUNEL signal, whereas the blue
fluorescence indicates the cell nuclei as stained by DAPI.
The excellent performance of CP1 NPs at the cellular level prompted us to further
investigate the in vivo behaviors of these NPs. The mouse model was established
by subcutaneously inoculating murine 4T1 cancer cells into the left back of BALB/c
mice. After intravenous (i.v.) injection of CP1 NPs (1 mg/mL based on CP1, 100 mL
per mouse), the mice were imaged with the Maestro system at various time points.
As shown in Figures 8A and 8B, thanks to the ability of NPs to accumulate in tumors
through a passive enhanced permeability and retention (EPR) effect, the fluores-
cence intensity of CP1 NPs in the tumor site increases over time upon excitation
at 455 nm. At 7 hr after CP1 NP injection the mice were sacrificed, and their tumors
and major tissues were isolated for ex vivo fluorescence imaging. Fluorescent
signals were mainly observed in tumor and liver tissues (Figure S25), which is
consistent with the in vivo imaging results, confirming the advantages of CP1
NPs in passive tumor targeting through EPR effect. At 7 hr after i.v. injection of
12
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different photosensitizer NPs (1 mg/mL based on photosensitizer, 100 mL per
mouse, each group of five mice), the 4T1 tumor sites of the mice were exposed
to white light (400–700 nm, 300 mW/cm2) for 10 min so that the photosensitizers
in the tumor sites could generate 1O2 to realize tumor therapy. We measured
the tumor size at different time points to evaluate the PDT efficacy of different
photosensitizer NPs. We note that SM1 NPs and Ce6 NPs could only hinder tumor
growth but could not reduce tumor size or inhibit tumor growth directly (Figure 8C),
as reported previously in the literature.3,4,58 Under the same conditions, CP1 NPs
could directly inhibit tumor growth, thus confirming their effectiveness in PDT.
After 15 days, the mice were sacrificed and the tumors were collected for histolog-
ical analysis. As shown in Figure 8D, H&E staining showed normal tumor tissue
morphology in tumor sections from mice in the saline group. Modest nucleus disso-
ciation and tissue necrosis were found in tumor sections from mice in both the SM1
NP and Ce6 NP groups. In contrast, tumor sections from mice in the CP1 NP group
exhibited serious tissue deterioration, confirming the higher PDT efficacy of CP1
NPs. The TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining data also
showed that the amount of apoptotic cells in tumor sections from mice in the
CP1 NP group was significantly increased compared with those in other groups
(Figure 8E). In addition, the pharmacokinetics results showed that both CP1 and
SM1 NPs can be automatically metabolized by the liver at around 1 week (Fig-
ure S26). Coupled with the negligible low in vivo dark toxicity (Figure S27), CP1
NPs are highly promising for application in image-guided photodynamic anticancer
therapy.
Conclusion
In summary, we have proposed the concept of polymerization-enhanced photosen-
sitization for the design of highly effective photosensitizers. In this work, four conju-
gated polymer photosensitizers, CP1–CP4, were prepared on the basis of the three
reported AIE molecules SM1–SM3 and SM4, which has no AIE features. Among
them, CP1 showed the highest fluorescence quantum yield of 6.2% and the most
effective 1O2 generation, which is 3.71-fold higher than that of Ce6. Coupled with
negligible dark in vivo toxicity, CP1 is promising for image-guided PDT application,
which has been further confirmed by both in vitro and in vivo results. Different from
most of the commercial photosensitizers, CP1 NPs exhibit excellent photostability,
which is very useful for photoinduced organic waste decomposition and photoin-
duced organic synthesis. The successful demonstration of conjugated-polymer-
based photosensitizers with enhanced photosensitizing effect and excellent stability
is anticipated to open up new opportunities for rational photosensitizer design and
applications.
EXPERIMENTAL PROCEDURES
Full experimental procedures are provided in the Supplemental Information.
SUPPLEMENTAL INFORMATION
Supplemental Information includes Supplemental Experimental Procedures, 27 fig-
ures, 2 tables, and 1 scheme and can be found with this article online at https://doi.
org/10.1016/j.chempr.2018.06.003.
ACKNOWLEDGMENTS
We thank the Singapore NRF Competitive Research Program (R279-000-483-281),
NRF Investigatorship (R279-000-444-281), National University of Singapore (R279-
000-482-133), the Program for Changjiang Scholars and Innovative Research
Chem 4, 1–15, August 9, 2018
13

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j.chempr.2018.06.003
Team in University (IRT13023) and the National Natural Science Foundation of China
(81220108015 and 51622305) for financial support.
AUTHOR CONTRIBUTIONS
W.W., D.M., and B.L. conceived the project. W.W., D.M., S.X., K., F.H., and X.L. per-
formed the experiments. W.W., D.M., D.K., and B. L. discussed results. W.W. and
B.L. wrote the manuscript.
DECLARATION OF INTERESTS
The authors declare no competing interests.
Received: January 31, 2018
Revised: March 7, 2018
Accepted: June 7, 2018
Published: June 28, 2018
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