Platinum-based photosensitizer with near-infrared aggregation-induced emission for synergistic photodynamic-chemo theranostics

Article abstract of DOI:10.1016/j.orgel.2021.106105

Photodynamic therapy (PDT) is of great interest as an emerging paradigm towards cancer treatment, owing to its advantages of minimal invasiveness and low toxicity. In this work, we incorporated cisplatin into an AIE-based photosensitizer (BT) and achieved

Full text of DOI:10.1016/j.orgel.2021.106105

Organic Electronics 92 (2021) 106105
Contents lists available at ScienceDirect
Organic Electronics
journal homepage: http://www.elsevier.com/locate/orgel
Platinum-based photosensitizer with near-infrared aggregation-induced
emission for synergistic photodynamic-chemo theranostics
a
a
b
b
a,*
Yuting Gao , Jiaxin Zhang , Zhenyan He , Liang Luo , Chunjie Yan
a
Engineering Research Center of Nano-Geomaterials of the Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan,
30074 China
4
b
National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074,
China
A R T I C L E I N F O
A B S T R A C T
Keywords:
Photodynamic therapy (PDT) is of great interest as an emerging paradigm towards cancer treatment, owing to its
advantages of minimal invasiveness and low toxicity. In this work, we incorporated cisplatin into an AIE-based
photosensitizer (BT) and achieved a highly efficient antitumor drug (BT-Pt). Possessing AIE characteristics, BT-Pt
exhibited NIR fluorescence with large Stokes shift in cells, which can guide the location of the drug. More
importantly, the ROS generation efficiency of BT-Pt has extremely been promoted with the fabrication of
cisplatin, compared with BT. As a result, BT-Pt demonstrated favorable therapeutic efficacy with a half maximal
AIE
Photosensitizer
Near-infrared emission
Large Stokes shift
Photodynamic-chemo theranostics
inhibitory concentration (IC50) value of 1.54 M for HeLa cells upon white light irradiation, attributed to its
μ
synergetic PDT and chemotherapy. The design strategy of such platinated photosensitizer showed great potential
in developing multifunctional anticancer drugs with combinatorial photodynamic–chemotherapy, especially
when ablating cisplatin resistant cancer cells and hypoxic tumors.
1
. Introduction
Photodynamic therapy (PDT), an emerging noninvasive therapeutic
design [9,10]. Unlike ACQ effects, the non-radiative decay pathway of
the AIE molecules is largely blocked in the aggregated state, which
promotes both the radiative pathway and intersystem crossing (ISC)
process of the excited states [11–13]. Hence, PSs with AIE characteristic
can improve illumination and ROS generation efficiency in
image-guided photodynamic therapy. In addition to PSs, light penetra-
tion depth and oxygen reliance also affect the efficacy of PDT towards
deep solid and hypoxic tumors, which limited its extensive application
in clinic [14,15]. Therefore, combinational therapy using two or more
therapeutic modalities has been demonstrated as a promising alternative
to eliminate the disadvantages of PDT [16–18].
Recently, PSs functionalized with transition metal complexes have
been designed with both photodynamic and chemo-therapeutic ability
for malignant tumor ablation, especially for platinum-based complexes
[19,20]. For example, cisplatin, a well-known chemotherapeutic drug, is
widely used in treatment of numerous human cancers including bladder,
head and neck, lung, ovarian, and testicular cancers [21]. However, its
drug resistance and numerous other undesirable side effects cannot be
ignored, such as severe kidney problems, cardiotoxocity, allergic re-
actions, decrease immunity to infections, gastrointestinal disorders,
hemorrhage, etc [22,23]. On the other hand, the distribution,
modality for cancer and non-oncological disorders treatments, has ob-
tained increased attention in clinical research, because of its advantages
of localized treatment and low systemic toxicity [1–4]. In PDT, the
photosensitizer (PS) located in malignant tissues would be excited by
light in a determined wavelength. Then the excited PSs can react with
the surrounding molecular oxygen or substrates to generates cytotoxic
1
singlet oxygen ( O
2
) and other reactive oxygen species (ROS) in target
tissues, which could oxide and destroy cellular biomolecules, such as
nucleic acids, lipids, and proteins, thus leading to cell death [5,6].
According to the above principles, the key elements of PDT are
photosensitizer, light and oxygen. Among them, PS is the most impor-
tant prerequisite determining the ROS generation efficiency to the
cancerous cell ablation. However, most conventional photosensitizers
(
PSs) suffer from the notorious aggregation-caused quenching (ACQ)
effect at high concentrations or in aggregate states, which dramatically
decreases their ROS generation efficiency and fluorescence quantum
yield [7,8]. To overcome such ACQ conundrum, aggregation-induced
emission (AIE) characteristics have been introduced in effective PSs
*
Corresponding author.
E-mail address: chjyan@cug.edu.cn (C. Yan).
https://doi.org/10.1016/j.orgel.2021.106105
Received 14 January 2021; Received in revised form 1 February 2021; Accepted 13 February 2021
Available online 18 February 2021
1
566-1199/© 2021 Elsevier B.V. All rights reserved.

Y. Gao et al.
Organic Electronics 92 (2021) 106105
column with hexane/dichloromethane (v/v = 1/1) to give compound 2
1
as a dense yellow oil (2.5 g). Yield: 88%. H NMR (400 MHz, CDCl
3
) δ
9
4
.75 (s, 1H), 7.63 (d, J = 8.7 Hz, 2H), 7.20–7.03 (m, 4H), 6.93–6.86 (m,
H), 6.85 (d, J = 8.8 Hz, 2H), 3.82 (s, 6H).
2
.1.3. 4-Methoxy-N-(4-methoxyphenyl)-N-(4-vinylphenyl)aniline (3)
Under a nitrogen atmosphere, a mixture of 4-(Bis(4-methoxyphenyl)
methyl)benzaldehyde
(2.00
g,
6.0
mmol)
and
methyl-
triphenylphosphonium bromide (6.43g, 18.0 mmol) in THF (40 mL) was
◦
stirred and cooled to 0 C for 30 min. Then a solution of t-BuOK (4.49 g,
◦
4
0.00 mmol) in 20 mL THF was injected slowly into the mixture at 0 C
Fig. 1. Proposed mechanism of BT-Pt for synergistic photodynamic-chemo
and stirred for another 30 min before it was moved to room temperature.
The progress of the reaction was monitored by thin layer chromatog-
raphy (TLC). After complete consumption of the starting material (12 h),
the reaction was quenched by the addition of dilute hydrochloric acid to
a neutral pH. Then the solvent was removed under vacuum and the raw
product was extracted three times by using dichloromethane (DCM) and
water. The organic layers were combined and dried by anhydrous
Theranostics.
accumulation, and metabolism of most platinum drugs in the body are
difficult to be tracked, making the study on platinum drugs a more
challenging issue. Thus, conjugating cisplatin to PSs can help monitor of
the drug location during the treatment [24,25]. What’s more, Pt-based
complexes have shown ability to promote rapid ISC process because of
heavy-atom effect, facilitating a more efficient ROS generation for
Pt-based PSs [26].
2 4
Na SO . After filtration, the solvent was removed under reduced pres-
sure, and the residue was purified by chromatography on a silica gel
column with Hexane/DCM (v/v = 2:1) to give compound 3 as a light
In this work, we introduced cisplatin into our AIE-based PS (BT) to
achieve a highly efficient antitumor drug (BT-Pt), which can perform not
only photodynamic therapy but also chemotherapy, as shown in Fig. 1.
The combination therapies of cisplatin fabricated PS can help alleviate
the drug-resistance and toxicity of cisplatin. Meanwhile, cisplatin can
facilitate the eradication of deep solid and hypoxic tumors, compen-
sating for each other’s drawbacks. What’s more, after the fabrication of
cisplatin, BT-Pt exhibited much better ROS generation efficiency than
BT. Remarkably, BT-Pt also showed near-infrared (NIR) fluorescence of
yellow oil drop (1.05 g, yield: 52.5%). 1H NMR (400 MHz, CDCl
3
) δ
7
.24–7.17 (m, 2H), 7.08–6.97 (m, 4H), 6.91–6.85 (m, 2H), 6.84–6.77
(
m, 4H), 6.62 (dd, J = 17.6, 10.9 Hz, 1H), 5.57 (dd, J = 17.6, 0.9 Hz,
1
H), 5.08 (dd, J = 10.9, 0.9 Hz, 1H), 3.78 (s, 6H).
2
.1.4. Synthesis of (E)-4-(2-(7-bromobenzo[c][1,2,5]thiadiazol-4-yl)
vinyl)-N,N-bis(4-methoxyphenyl)aniline (4)
Under a nitrogen atmosphere, a mixture of compound 3 (662.8 mg,
2
.0 mmol), 4,7-Dibromo-2,1,3-Benzothidiazole (646.7 mg, 2.2 mmol)
>
650 nm, providing the possibility of real-time monitor of drug uptake
and Palladium (II) Acetate (54.0 mg, 0.24 mmol), NaOAc (3.28 mg, 40
in deep penetration with low fluorescence interference.
mmol), Bu
4
NBr (0.71 g, 2.2 mmol) in DMF (80 mL) was stirred and
◦
heated to 100 C for 24 h. After cooling down to room temperature, the
solvent was removed under reduced pressure and the raw product was
extracted three times using dichloromethane (DCM) and water. The
2
. Experimental section
The details of materials and instruments can be found in the Sup-
2 4
organic layers were combined and dried by anhydrous Na SO . After
porting Information (SI). The synthesis methods of the BT-Pt and rele-
vant in vitro study are described below.
filtration, the solvent was removed under reduced pressure, and the
residue was purified by chromatography on a silica gel column with
Hexane/DCM (v/v = 3:1) to give compound 3 as an red-purple powder
1
2
2
.1. Synthesis methods
(370 mg, yield: 34%). H NMR (400 MHz, CDCl
3
) δ 7.84 (d, J = 16.3 Hz,
1
H), 7.77 (d, J = 7.7 Hz, 1H), 7.52–7.33 (m, 4H), 7.12–7.01 (m, 4H),
13
.1.1. 4-Methoxy-N-(4-methoxyphenyl)-N-phenylaniline (1)
6.91 (d, J = 8.7 Hz, 2H), 6.87–6.76 (m, 4H), 3.79 (s, 6H). C NMR (101
MHz, CDCl
) δ 156.13, 153.79, 152.97, 149.07, 140.35, 133.92, 132.37,
130.83, 128.92, 127.81, 126.90, 125.75, 120.60, 119.84, 114.73,
The intermediate compound 1 was synthesized according to our
3
previous report [27]. 4-iodoanisole (7.20 g, 30.76 mmol), aniline (1.14
mL, 12.49 mmol), ophenanthroline (0.45 g, 2.30 mmol), cuprous iodide
3 2
111.27, 55.48. HRMS (APCI): m/z calcd for C28H22BrN O S, 546.0629;
(
0.48 g, 2.52 mmol) and potassium hydroxide (5.60 g, 100.00 mmol)
were dissolved in a round-bottom flask in 100 mL toluene. The mixture
was refluxed under N atmosphere and the progress of the reaction was
found: 546.0632.
2.1.5. Synthesis of (E)-4-methoxy-N-(4-methoxyphenyl)-N-(4-(2-(7-
(pyridin-4-yl)benzo[c][1,2,5]thiadiazol-4-yl)vinyl)phenyl)aniline (BT)
Under an nitrogen atmosphere, a mixture of compound 4 (320 mg,
0.58 mmol), pyridine-4-boronic acid (108.4 g, 0.88 mmol) and Pd
2
monitored by thin layer chromatography (TLC). When the reaction was
completed, the mixture was filtered and the solvent was removed under
vacuum. The residue was then purified by column chromatography on
silica gel column (hexane/dichloromethane, v/v = 3/1) to afford the
(PPh
3
)
4
(68.0 mg, 0.06 mmol) in THF (30 mL) was stirred and heated to
1
◦
product 1 as a light yellow powder (2.9 g). Yield: 76%. H NMR (400
60 C, then a solution of potassium carbonate (1.65 g, 12.0 mmol) in 6
mL water was injected slowly and the mixture was heated to refluxed for
8 h. After it was cooled, 100 mL water was added to quench the reaction
and the raw product was extracted three times using dichloromethane
(DCM) and water. The organic layers were combined and dried by
MHz, CDCl
3
) δ 7.16 (t, J = 7.9 Hz, 1H), 7.04 (d, J = 8.8 Hz, 2H), 6.93 (d,
J = 8.1 Hz, 1H), 6.90–6.72 (m, 2H), 3.79 (s, 3H).
2
.1.2. 4-(Bis(4-methoxyphenyl)methyl)benzaldehyde (2)
The intermediate compound 2 was synthesized according to our
2 4
anhydrous Na SO . After filtration, the solvent was removed under
previous report [27]. To the stirred solution of 1 (2.6 g, 8.5 mmol) in
reduced pressure, and the residue was purified by chromatography on a
silica gel column with Hexane/ethyl acetate (v/v = 4:1) to give com-
pound BT as a purple solid (150 mg, yield: 48%). 1H NMR (400 MHz,
◦
DMF (40 mL), POCl3 (1.1 mL,. 12.0 mmol) was added at 0 C under Ar.
◦
The reaction was performed at 90 C and monitored by TLC. When the
reaction is completed, 50 mL ice water was added slowly to quench the
reaction and the raw product was extracted using dichloromethane and
water. The organic layers were combined and dried using anhydrous
CDCl
3
) δ 8.80 (d, J = 6.1 Hz, 2H), 8.00 (d, J = 6.2 Hz, 2H), 7.95 (d, J =
16.3 Hz, 1H), 7.83 (d, J = 7.5 Hz, 1H), 7.75 (d, J = 7.7 Hz, 1H), 7.53 (d,
J = 16.3 Hz, 1H), 7.48 (d, J = 8.7 Hz, 2H), 7.12–7.08 (m, 4H), 6.94 (d, J
1
3
Na
2
4
SO . After filtration, the solvent was removed under reduced pres-
= 8.7 Hz, 2H), 6.88–6.84 (m, 4H), 3.82 (s, 6H). C NMR (101 MHz,
sure, and the residue was purified by chromatography on a silica gel
CDCl
3
) δ 156.18, 153.91, 153.37, 149.76, 149.19, 140.29, 134.48,
2

Y. Gao et al.
Organic Electronics 92 (2021) 106105
Scheme 1. Synthetic routes to BT-Pt.
1
1
5
32.39, 129.18, 128.86, 127.96, 126.95, 125.18, 123.65, 120.79,
room temperature, the mixture was poured into diethyl ether. The
precipitate was then washed with diethyl ether three times and dried
under reduced pressure to afford the product as a dark purple solid (81
+
19.75, 114.73, 55.48. HRMS (ESI ): m/z calcd for C33
H
26
N
4
O
2
S,
43.1810; found: 543.1845.
mg, yield: 64%). 1H NMR (400 MHz, DMSO‑d
6
) δ 8.82 (d, J = 6.9 Hz,
2
.1.6. Synthesis of BT-Pt
2H), 8.26 (d, J = 6.9 Hz, 2H), 8.22 (d, J = 7.6 Hz, 1H), 8.09 (d, J = 16.3
Hz, 1H), 8.00 (d, J = 7.6 Hz, 1H), 7.59 (d, J = 16.3 Hz, 1H), 7.54 (d, J =
8.8 Hz, 1H), 7.15–7.03 (m, 2H), 6.99–6.89 (m, 2H), 6.77 (d, J = 8.8 Hz,
2H), 4.68 (s, 3H), 4.30 (s, 3H), 3.74 (s, 6H).
In a 25 mL round-bottom flask, a mixture of cisplatin (61.20 mg,
0
.204 mmol) and silver nitrate (34.68 mg, 0.204 mmol) in N,N-
◦
dimethylformamide (DMF) (30 mL) was stirred and heated to 60
C
1
3
for 24 h under a nitrogen atmosphere. After cooling to room tempera-
ture, the reaction mixture was separated by centrifugation. The super-
natant was added with compound BT (84.56 mg, 0.156 mmol) and
C NMR (101 MHz, DMSO‑d
6
) δ 156.67, 153.57, 153.16, 153.06,
150.37, 149.51, 146.57, 139.87, 133.01, 128.67, 128.51, 127.72,
+
127.64, 126.43, 125.46, 123.67, 118.80, 115.53, 55.73. HRMS (ESI ):
◦
+
stirred at 60 C for 24 h under a nitrogen atmosphere. After cooling to
m/z calcd for C33
H32ClN
6
O
2
PtS , 806.1638; found: 806.1634.
Fig. 2. (a) UV–vis spectra of BT-Pt. (b) Fluorescence (FL) spectra of BT-Pt (10
μ
M) in toluene/DMSO mixtures with different ethanol fractions (f
t
). λex = 510 nm. (c)
Plot of peak intensity ratio I/I
0
versus toluene fraction, where I
0
is the emission peak intensity in pure DMSO. (d) FL spectra of BT-Pt (10
μM) in the presence of
different amounts of BSA. λex = 510 nm.
3

Y. Gao et al.
Organic Electronics 92 (2021) 106105
Fig. 3. UV–vis absorption spectra of ABDA in BT-Pt (a), BT (b) and blank (c) solutions irradiated for different durations with white light irradiation (300–800 nm, 4
ꢀ 2
mW cm ). (d) Corresponding absorbance of ABDA aqueous solutions at 379 nm in BT-Pt, BT, and blank solutions for different durations. [BT-Pt] = [BT] = 10
ABDA] = 100 M.
μM,
[
μ
2
.2. Cellular imaging by CLSM
molecular orbital (HOMO) – lowest unoccupied molecular orbital
LUMO) separation, thus facilitate the ISC process [30]. Herein, we
designed a D– –A structure-based PDT PSs, BT-Pt, as depicted in Scheme
1. Possessing special propeller-like molecular structure and good
electron-donating ability, triphenylamine (TPA) is recognized as an
excellent donor to construct AIE fluorochrome. 2,1,3-benzothiadiazole,
an electron acceptor, was conjugated to TPA via ethylenic bond by heck
(
HeLa cells were cultured in chamber (LAB-TEK, Chambered Cover
π
◦
Glass System) at 37 C. After 80% confluence, the medium was replaced
with BT-Pt in DMEM (10 M) and incubated for 12 h. Then the cells were
μ
washed with PBS for three times and imaged by using Olympus FV3000
microscope with × 100 objective lens.
reaction to give structures of D- -A configuration, which can help
π
2
.3. Cell cytotoxicity assay
redshift molecular absorption and emission peaks through intra-
molecular charge transfer (ICT) process. Then after a suzuki coupling
reaction with pyridine-4-boronic acid (BT), cisplatin was coupled with
BT to achieve BT-Pt with synergistic treatment effects. The synthetic
routes to the photosensitizer BT-Pt were shown in Scheme 1, and the
structural characterization of BT and BT-Pt were shown in the Sup-
porting Information (Fig. S1-S6).
The cytotoxicity of the BT-Pt and BT in the absence and presence of
white light irradiation was assessed by MTT assays. HeLa cells were
seeded in 96-well plates and cultured in standard medium containing
ꢀ 1
1
1
0% FBS and 1% antibiotics (penicillin, 10,000 U mL , streptomycin
ꢀ 1
◦
2
0 mg mL ) for 24 h (37 C, 5% CO ). The cells were then incubated
with PS solutions at various concentrations (diluted with standard me-
dium) in the dark for 12 h. Then the PS solutions were replaced with
fresh standard DMEM before it is exposed or unexposed (in dark) to
3.2. AIE properties
ꢀ
2
white light (300–800 nm, 4 mW cm ) for 40 min. After the cells were
The photophysical properties of the BT-Pt were firstly investigated.
Being fabricated with cisplatin, BT-Pt displayed much better solubility in
polar solvents, such as, DMSO, DMF and water, compared with BT. BT-Pt
exhibited a maximum absorption peak at 515 nm and negligible fluo-
rescence in DMSO (Fig. 2a and b). When we added toluene, a poor
solvent to BT-Pt, and increased the volume ratio of toluene/DMSO
further cultured for 6 h, 10
μ
L of freshly prepared MTT (5 mg mL 1
ꢀ
)
solution was added into each well. After incubation for 4 h, the mixture
solution was carefully removed, and DMSO (150 L) was added to
μ
dissolve the formazan formed. The absorbance of MTT at 570 nm was
measured by the microplate reader (Varioskan LUX, Thermo Scientific,
USA).
mixtures (f ), the emission intensity (I) of BT-Pt was gradually enhanced
t
t
at a wavelength of ~700 nm (Fig. 2b). When f reached 90%, the
3
. Results and discussion
emission peak intensity increased about 18 times compared with that in
pure DMSO (Fig. 2c). Such phenomenon can be ascribed to AIE effect,
which fluorogens exhibit very weak emission in dissolved molecular
state but become highly emissive in aggregated state due to the re-
striction of intramolecular motion (RIM). It is noteworthy that BT-Pt
shows large Stokes shifts of 185 nm in aggregated states, contributing
to the minimized interference between excitation and emission, which
are favorable for bioimaging.
3
.1. Molecular design and synthesis
As noted above, the design of PS plays a predominate role in PDT
process. According to the previous research, the efficient ISC process
from the lowest excited singlet state (S ) to the lowest triplet state (T ) is
crucial for PS to generate 1
[28,29]. Theoretically, introduction of a
donor– –acceptor (D– –A) structure can help decrease the energy gap
between the S state and the T state through the highest occupied
1
1
O
2
π
π
In addition, when bovine serum albumin (BSA), a negatively charged
albumen with hydrophobic sites, was added into BT-Pt aqueous solution,
1
1
4

Y. Gao et al.
Organic Electronics 92 (2021) 106105
Fig. 4. CLSM images of HaLa cells after incubation with BT-Pt (10
μ
M)for 6h. (a) Red channel (600–700 nm), λex = 561 nm. (b) Bright channel. (c) Merged image.
The scale bar is 10
μ
m. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
verified by the absorption spectra of BT-Pt in the absence and presence
of BSA, which is shown in Fig. S7. The bathochromic-shift and extended
absorption tails indicated the interaction of the BT-Pt and BSA, and the
fomation of aggregates (Mie effect), respectively.
3
.3. Singlet oxygen generation
We next investigated the ability of BT-Pt in singlet oxygen generation
by employing 9,10-anthracenediyl-bis(methylene)dimalonic acid
ABDA) as 1
probe. ABDA is a widely-used ROS probe that can
2
selectively react with O and simultaneously induce a corresponding
(
O
2
1
decrease in its absorbance. When an aqueous solution of ABDA is
exposed to white light irradiation in the presence of BT-Pt, the charac-
teristic absorption peaks of ABDA decrease promptly (Fig. 3a), indi-
cating the efficient production of 1
2
O . In contrast, the decline in
absorption peaks of ABDA containing BT was much slower than that of
BT-Pt at the same conditions (Fig. 3b). We can observe from Fig. 3d that
the decomposition rate of ABDA in BT-Pt solution was about 8 times
1
faster than BT. Such boost in O
2
generation of BT-Pt should be ascribed
to the platinization of BT, since the spin orbit coupling of Pt can promote
effective singlet-to-triplet transition and facilitate the generation of
Fig. 5. Cell viability of HeLa cells pretreated with increasing doses of cisplatin
and BT-Pt in the absence and presence of white light irradiation (300–800 nm,
1
singlet oxygen from molecular oxygen. Besides, negligible
2
O was
ꢀ
2
4
mW cm , 40 min).
detected for ABDA alone upon the same light irradiation, excluding the
influence of light towards ABDA (Fig. 3c).
we can also observe an obvious emission enhancement at emission peak
at ~670 nm (Fig. 2d). Such increase in fluorescence could be attributed
to the interaction between BT-Pt with BSA, which restricted the intra-
molecular motions of the molecules, and consequently blocked the
nonradiative decay and turned on the fluorescence. This can be further
3.4. PDT efficacy in vitro
To investigate the cell uptake of BT-Pt, the cellular imaging in vitro
was studied by confocal laser scanning microscopy (CLSM). After we
◦
incubated HeLa cells with BT-Pt for 6 h at 37 C in the culture medium,
Fig. 6. Detection of intracellular ROS generation in HeLa cells incubated with or without BT-Pt upon different irradiation time (λex = 561 nm, laser power: 10%). The
Green channel is fluorescence of DCF (λex = 488 nm; λem = 500–560 nm). Scale bar: 30
μ
m. (For interpretation of the references to colour in this figure legend, the
reader is referred to the Web version of this article.)
5

Y. Gao et al.
Organic Electronics 92 (2021) 106105
their images were captured by CLSM with excitation at 561 nm, and the
fluorescent signals were collected from 650 to 750 nm. We can observe
obvious NIR fluorescence signals from cell cytoplasm in Fig. 4, indi-
cating effective cellular uptake of BT-Pt.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.orgel.2021.106105.
To demonstrate synergistic antitumor effect of BT-Pt, the cytotox-
icity of BT-Pt towards HeLa cells in the absence and presence of light
irradiation was examined by standard 3-(4,5-dimethyl-2-thiazolyl)-2,5-
diphenyl tetrazolium bromide (MTT) assays. HeLa cells were incubated
with escalated doses of BT-Pt for 6 h, followed by washing with PBS and
irradiation or not. As shown in Fig. 5, BT-Pt induced dose-dependent cell
death with a half maximal inhibitory concentration (IC50) value of 1.54
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μ
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