“Turn-On” Activatable AIE Dots for Tumor Hypoxia Imaging

Article abstract of DOI:10.1002/chem.201902296

A hypoxia-responsive fluorescence probe of amphiphilic PEGylated azobenzene caged tetraphenylethene (TPE) for tumor cell imaging is reported; it possesses excellent solubility in aqueous medium due to the easy formation of micelles by self-assembly. The f

Full text of DOI:10.1002/chem.201902296

A Journal of
Accepted Article
Title: “Turn-On” Activatable AIE Dots for Tumor Hypoxia Imaging
Authors: Tianhao Xue, Xiangqian Jia, Jilei Wang, Jingyuan Xiang, Wei
Wang, Juanjuan Du, and Yaning He
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To be cited as: Chem. Eur. J. 10.1002/chem.201902296
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“Turn-On” Activatable AIE Dots for Tumor Hypoxia Imaging
Tianhao Xue┴,[a] Xiangqian Jia┴,[b] Jilei Wang,[a] Jingyuan Xiang,[a] Wei Wang, [a] Juanjuan Du*[b] and
Yaning He*[a]
┴ These authors contributed equally to this work
Abstract: This communication reported
a
hypoxia-responsive
Hypoxia is among the most important features of malignant
tumors. [10-12] As the tumor grows in an exaggerated way, interior
cells of the tumor rapidly outgrow their blood supply, leading to a
fluorescence probe of amphiphilic PEGylated azobenzene caged
tetraphenylethene (TPE) for tumor cell imaging, which possessed
excellent solubility in aqueous medium due to the easily forming
micelles by self-assembly. Due to the fluorescence resonance
energy transfer (FRET) process, the fluorescence of the azobenene
caged AIE fluorogen will be quenched efficiently. When cultured with
tumor cells, the azo-bond is reduced under hypoxia conditions and
the fluorescence of AIE fluorogen recovers dramatically. Besides
using UV light, near-infrared (NIR) light can also be used as the
excited light resource to generate the fluorescence due to the two
photon fluorescence imaging process.
reduced
oxygen
concentration
in
the
intratumoral
microenvironment. Furthermore, tumor hypoxia alters cancer cell
metabolism and contributes to cancer cell invasion, metastasis,
and therapy resistance. Therefore, sensing tumor hypoxia is
particularly important for tumor diagnosis and prognosis. [13-15]
Azobenzene derivatives with intense absorption bands in the
UV-visible light region often serve as non-fluorescent energy
[16]
acceptors to quench fluorophores in proximity.
The
azobenzene quenched system has been used for proteolysis
[17]
and nucleic acid hybridization detection.
What’s more, the
azobenzene chromophore can be reduced efficiently in the
Different from the conventional fluorophores that were self-
quenched in an aggregation state, aggregation-induced
emission (AIE) fluorogens emit strong fluorescence in
aggregation states, due to the restriction of intramolecular
motions. [1-3] For example, the tightly packed AIEgens in the core
of AIE nanoparticles yields high fluorescence brightness, which
[18-24]
hypoxic microenvironment,
to recover the fluorescence of
the system. Therefore, the reducible azobenzene-containing
fluorophores can be used as ‘‘off–on’’ fluorescent probes for the
detection of tumor hypoxia. [14, 25-31]
[4,5]
can be 10−40 times brighter than that of quantum dots.
Additionally, AIE aggregates show an excellently linear
concentration-dependent increase in brightness and high
[6]
resistance to photobleaching. Moreover, due to the large two-
photon absorption cross-sections, AIE aggregates are especially
[7]
suitable for two-photon fluorescence imaging.
Therefore, AIE
fluorogens have recently become appealing fluorescence agents
for bioimaging. Among them, AIE dots are nanoparticles with an
AIE fluorogen (AIEgens) core and biocompatible materials as
the shell. [6-8] Due to the high brightness and biocompatibility, the
AIE dots have gained great success in bioimaging. However,
[9]
studies on AIE dot based biosensors remain rare. Developing
novel environment-sensitive AIE dots is in need to further
expand the application of these exceptional fluorescence
nanoaggregates. Therefore, in this work, we present an
activatable AIE dot (aAIE dot), which is an organic dot that can
be activated to emit AIE fluorescence in response to
environmental cues.
Scheme 1. Fabrication of activatable polymeric AIE aggregates via self-
assembly in aqueous solution.
[a]
T.H. Xue, J.L. Wang, J.Y. Xiang, W. Wang, Dr. Y.N. He
Department of Chemical Engineering
Key Laboratory of Advanced Materials (MOE)
Tsinghua University, Beijing, 100084, China.
E-mail: heyaning@mail.tsinghua.edu.cn
X.Q. Jia, Dr. J.J. Du
School of Pharmaceutical Sciences
Tsinghua University, Beijing, 100084, China.
Email: dusps@mail.tsinghua.edu.cn
Although conventional fluorophores caged by azobenzene
have been explored as hypoxia-sensitive fluorescent probes, the
azobenzene caged AIE fluorescent probe has not been reported
yet. In this communication, we reported a “turn-on” hypoxia-
responsive fluorescence probe of PEGylated azobenzene caged
tetraphenylethene (TPE) (Scheme 1). Due to the amphiphilic
chemical structure, this PEGylated azobenzene-TPE derivative
can form nanoaggregates by self-assembly in the aqueous
medium, yielding stable azobenzene-caged aAIE dots. The
fluorescence of the azobenzene-caged AIE fluorogen will be
[b]
Supporting information for this article is given via a link at the end of
the document.
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quenched efficiently because of fluorescence resonance energy
transfer (FRET) process. In hypoxic tumor microenvironment,
the overexpressed azoreductase cleaves the azobenzene
moieties, recovering the fluorescence of the AIE fluorogen. In
addition, we have demonstrated that this “turn-on” fluorescent
probe can be used for two-photon imaging with near-infrared
(NIR) light as the excitation light source.
The hypoxia-responsive fluorescence probe of amphiphilic
PEGylated azobenzene caged TPE (PEG-Azo-TPE) was
synthesized by the macromolecular azo coupling reaction
between a PEG diazonium salt and a TPE modified aniline
(Scheme 1, the detailed synthesis route is shown in Figure S1).
The macromolecular azo coupling reaction has been proved to
The resulted PEG-Azo-TPE is amphiphilic, with
hydrophobic TPE head and a hydrophilic PEG tail linked by the
azobenzene linker. Thus, this amphiphilic macromolecule can be
self-assembled into micelles in aqueous solutions, yielding
azobenzene-caged TPE aAIE dots stabilized by biocompatible
PEG. The TEM image of the self-assembled aggregates is
shown in Figure 1. Uniform nanoparticles with a mean diameter
around 90 nm were obtained (estimated statistically from the
TEM image). This observation is consistent with the results of
the dynamic light scattering (DLS) measurement (Figure S5).
a
be a very efficient method to prepare amphiphilic diblock
[32-35]
copolymers.
Here, we use the macromolecular azo
coupling reaction to obtain the designed PEG-Azo-TPE. A
diazonium salt of PEG-NH2 was prepared by adding an aqueous
solution of sodium nitrite into a mixture of PEG-NH2, HCl (36%)
and H2O. Then the diazonium salt of PEG-NH2 was added
dropwise into the solution of TPE modified aniline to afford PEG-
Azo-TPE. The synthetic details of PEG diazonium salts and TPE
1
modified aniline are shown in the supporting materials. The H
NMR spectra of the prepared PEG-Azo-TPE is shown in Figure
S2. The characteristic peaks corresponding to the protons of the
azobenzene caged TPE moiety (6.63-8.12 ppm) and the PEG
chain (3.50-3.70 ppm) indicate the successful construction of
PEG-Azo-TPE. Figure S3 shows the gel permeation
chromatography (GPC) of PEG monomethyl ether and PEG-
Azo-TPE, demonstrating the molecular weight gain after
conjugating the Azo-TPE groups to the PEG chain. Figure S4
reveals the UV−visible absorption spectrum of PEG-Azo-TPE.
The obvious absorption in the visible region (λmax = 438 nm) can
be attributed to the typical absorption behavior of the pseudo-
stilbene type of azo chromophores corresponding to the π-π*
transition. Collectively, these evidences prove that PEG-Azo-
TPE is successfully synthesized.
Figure 2. UV-visible absorption (a) and fluorescence (b) spectra of the self-
assembled nanoaggregates in aqueous solution before and after enzymatic
reduction reaction in the hypoxic condition (the inserts represent the
photographs of the aggregate aqueous solutions before and after the
reduction reaction).
It has been reported that the azo bond (N=N) in azobenzene
compounds can be efficiently reduced by azoreductase
treatment in the hypoxic condition. [22, 24, 36-37] To test whether the
cleavage of PEG-Azo-TPE can reactivate TPE fluorescence, the
UV-visible and fluorescent spectra of PEG-Azo-TPE self-
assembly aggregates were measured before and after enzyme
treatment in hypoxic condition (Figure 2). The absorption peak in
the visible region attributed to the pseudo-stilbene type azo
chromophores disappeared after the reduction reaction (Figure
2(a)), verifying the cleavage of the azobenzene chromophores.
In addition, the fluorescence spectrum of PEG-Azo-TPE showed
no observable emission with excitation light of 365 nm red line of
Figure 1. Typical TEM image of the self-assembly nanoparticles of PEG-Azo-
TPE in aqueous solution.
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Figure 2(b)), validating our hypothesis that the azobenzene
moiety effectively quenched the fluorescence of the TPE dots.
After the treatment with enzyme, the fluorescence of TPE at 465
nm re-appeared when excited with 365 nm light (blue line of
Figure 2(b)). The ON/OFF ratio of the fluorescence emission
was more than 25 fold. Strong fluorescence could be observed
by naked eyes, which was shown in the insert of Figure 2(b).
The reduction product TPE-NH2 has been detected by mass
spectrometry (Figure S6). The destruction of the micelles also
can be observed after the enzyme treatment (Figure S7). All of
above results demonstrated that PEG-Azo-TPE nanoparticles
could be used as a “turn-on” fluorescence probe triggered by
azoreductase.
The activatable fluorescence can be also observed with two-
photon excitation with near-infrared (NIR) light. NIR light
penetrates deeper into the tissue and is less detrimental to the
biomolecules. Thus, two-photon fluorescence imaging may
provide a possible optical window for in-vivo imaging with deep
tissue penetration and minimal phototoxicity to the living cells.
Figure S8 shows the two-photon fluorescence spectrum of the
PEG-Azo-TPE aggregates in aqueous solution after the enzyme
treatment. No fluorescence could be observed before the
reduction reaction due to the FRET-mediated quenching. After
the enzyme treatment, the emission peak at 465 nm was
observed when excited with 760 nm light, in consistent with the
fluorescence emission of TPE dots.
dramatically increased fluorescence. This is due to the
generation of upregulated azoreductase in tumor hypoxia
mediated the cleavage of the azobenzene linkage to restore the
fluorescence of TPE dots. And we confirmed the existence of
azoreductase in cells culture supernatant by using a continuous
spectrophotometric rate assay (Figure S9). The determination
details are shown in the supporting materials. These results
clearly indicate that the PEG-Azo-TPE can be utilized to
distinguish the hypoxic status from tumor tissue via the detection
of endogenous azoreductase.
In the cytotoxicity experiments, we incubated PEG-Azo-TPE
with HeLa cells under normoxic and hypoxic environment. In
both conditions, HeLa cells show high viability (higher than 80%)
in PEG-Azo-TPE solutions with concentrations up to 0.8 mg/mL
(Figure S10), indicating PEG-Azo-TPE has minimal cytotoxicity
against HeLa cells.
Figure 3. Microscopy images of adherent A549 cells treated with PEG-Azo-
TPE probes under normoxia (20% O2) and hypoxia (1% O2).
Figure 4. Fluorescence microscopy images of Hela multicellular tumor
spheroids (MCTS) incubated with PBS or PEG-Azo-TPE.
As the azoreductases are reportedly over-expressed in
[38-41]
hypoxic cancer cells,
we further tested whether PEG-Azo-
The multicellular tumor spheroid (MCTS) model, a well-
established 3D cell culture method, has been proved superiority
TPE aggregates can be reduced to restore TPE fluorescence in
hypoxic tumor cell cultures. Figure 3 shows the fluorescence
images of adherent A549 cells after the incubation with PEG-
Azo-TPE under different oxygen concentrations. A549 cells
treated with the PEG-Azo-TPE nanoparticles under normoxic
conditions (20% v/v O2) show negligible background
fluorescence. This can be attributed to the negligible expression
of azoreductase in A549 cells under normoxic conditions. Under
normoxic conditions, the probe itself emits very weak
fluorescence, leading to no observable fluorescence in the cell
culture. In contrast, A549 cells treated with the PEG-Azo-TPE
nanoparticles under hypoxic conditions (1% v/v O2) produced
over monolayer cell culture models to recapitulate in vivo tumor
[42, 43]
growth.
In particular, MCTS mimics in vivo tumor models
by developing hypoxic and apoptotic/necrotic areas as
a
consequence of the formation of oxygen and nutrient gradients.
[44, 45]
To investigate whether PEG-Azo-TPE can be used to
image the hypoxia area in the MCTS, we incubated PEG-Azo-
TPE with preformed MCTS of HeLa cells for different time.
Figure 4 shows the fluorescence microscopy images of HeLa
MCTS with or without the treatment of PEG-Azo-TPE. In
comparison to the HeLa MCTS treated with PBS, HeLa MCTS
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treated with PEG-Azo-TPE shows significantly higher
fluorescence emission. Moreover, the fluorescence intensity in
the MCTS gradually increased with prolonged incubation time up
to 72 hours. The time-dependent increase in fluorescence
intensity may be attributed to the sustained release of the TPE
AIE fluorogen from the PEG-Azo-TPE aggregates. The MCTS
formed with A549 cells were used to verify this phenomenon.
Figure S11 shows the fluorescence images of A549 MCTS after
the incubation with PBS or PEG-Azo-TPE. Similarly, significantly
higher fluorescence was observed in the MCTS treated with
PEG-Azo-TPE in comparison to the control group. These
observations demonstrated that PEG-Azo-TPE serves as a
“turn-on” fluorescence probe to detect hypoxia area in tumor 3D
culture.
The two-photon fluorescence imaging was carried out with
the HeLa MCTS. Figure 5 represents the microscopy images of
HeLa MCTS treated with PEG-Azo-TPE nanoparticles excited
with 760nm laser. Strong fluorescence can be observed after the
HeLa MCTS was incubated with the PEG-Azo-TPE for 72h. On
the contrary, no detectable fluorescence was observed in HeLa
MCTS without PEG-Azo-TPE treatment. This experiment verified
that PEG-Azo-TPE could be used as a hypoxia probe in two-
photon fluorescence imaging.
fluorophores, this work opens up new possibilities for tumor
imaging with AIE fluoreogens, such as deep-tissue imaging.
Moreover, nanoparticles are reported to accumulate in some
tumor tissues by the enhanced permeability and retention (EPR)
effect. The nano-scale PEG-Azo-TPE dots may have further
advantages over conventional small molecular probes. Future
research is ongoing to explore the unique behavior of the nano-
scale hypoxia probe.
Acknowledgements
The authors gratefully acknowledge financial support from the
National Key Research and Development Program of China
(Grant Nos. 2017YFA0701303, 2018YFA0209700), and the
National Natural Science Foundation of China (Grant Nos.
51873097 and 21674058).
Keywords: hypoxia • fluorescence probe • self-assembly • azobenzene • AIE
[1]
[2]
[3]
[4]
[5]
D. Ding, K. Li, B. Liu, B. Z. Tang, Accounts Chem Res 2013, 46, 2441-
2453.
J. Mei, Y. N. Hong, J. W. Y. Lam, A. J. Qin, Y. H. Tang, B. Z. Tang, Adv
Mater 2014, 26, 5429-5479.
X. Gu, R. T. K. Kwok, J. W. Y. Lam, B. Z. Tang, Biomaterials 2017, 146,
115-135.
K. Li, W. Qin, D. Ding, N. Tomczak, J. L. Geng, R. R. Liu, J. Z. Liu, X. H.
Zhang, H. W. Liu, B. Liu, B. Z. Tang, Sci Rep-Uk 2013, 3, 1150.
D. Wang, J. Qian, W. Qin, A. J. Qin, B. Z. Tang, S. L. He, Sci Rep-Uk
2014, 4, 4279.
[6]
[7]
[8]
G. X. Feng, B. Liu, Accounts Chem Res 2018, 51, 1404-1414.
X. Lou, Z. Zhao, B. Z. Tang, Small 2016, 12, 6430-6450.
S. J. Chen, H. Wang, Y. N. Hong, B. Z. Tang, Mater Horiz 2016, 3, 283-
293.
[9]
X. Wang, Y. Y. Yang, Y. P. Zhuang, P. Y. Gao, F. Yang, H. Shen, H. X.
Guo, D. C. Wu, Biomacromolecules 2016, 17, 2920-2929.
[10] H. K. Eltzschig, P. Carmeliet, New Engl J Med 2011, 364, 656-665.
[11] D. M. Gilkes, G. L. Semenza, D. Wirtz, Nat Rev Cancer 2014, 14, 430-
439.
[12] S. K. Parks, Y. Cormerais, J. Pouyssegur, J Physiol-London 2017, 595,
2439-2450.
[13] Y. Zeng, J. W. Ma, S. J. Zhang, D. C. Wu, Curr Med Chem 2016, 23,
1775-1800.
Figure 5. Microscopy images of HeLa multicellular tumor spheroids (MCTS)
treated with PEG-Azo-TPE probes excited with 760nm light. The HeLa
multicellular tumor spheroids (MCTS) were incubated with PBS and PEG-Azo-
TPE for 72h.
[14] T. Thambi, J. H. Park, D. S. Lee, Chem Commun 2016, 52, 8492-8500.
[15] C. S. Wang, Z. H. Wang, T. Zhao, Y. Li, G. Huang, B. D. Sumer, J. M.
Gao, Biomaterials 2018, 157, 62-75.
[16] J. T. Wu, Y. Tan, Y. H. Xie, Y. Wu, R. Zhao, Y. Y. Jiang, C. Y. Tan,
Chem Commun 2013, 49, 11379-11381.
In summary, a hypoxia-responsive “turn-on” fluorescence
probe of PEGylated azobenzene-caged tetraphenylethene
(PEG-Azo-TPE) for tumor hypoxia imaging was reported. This
amphiphilic PEGylated macromolecule forms nano-scale PEG-
stabilized azobenene-caged aAIE dots by self-assembly in the
aqueous medium. The fluorescence of the azobenene-caged
aAIE dots is efficiently quenched, due to the FRET-mediated
quenching. When incubated with tumor cells, the azo-bond is
reduced under hypoxia conditions to recover fluorescence of the
core AIE fluorogen. In addition to UV light, near-infrared (NIR)
light can be used as the excitation light source for two-photon
fluorescence imaging with PEG-Azo-TPE as the hypoxia probe.
As AIE aggregates have distinct advantages over other
[17] J. W. J. Li, X. H. Fang, S. M. Schuster, W. H. Tan, Angew Chem Int
Edit 2000, 39, 1049-1052.
[18] S. H. Lee, E. Moroz, B. Castagner, J. C. Leroux, J Am Chem Soc 2014,
136, 12868-12871.
[19] S. Li, J. L. Wang, J. J. Shen, B. Wu, Y. N. He, Acs Macro Lett 2018, 7,
437-441.
[20] J. L. Wang, B. Wu, S. Li, Y. N. He, J Polym Sci Pol Chem 2017, 55,
2450-2457.
[21] P. Kulkarni, M. K. Haldar, S. You, Y. Choi, S. Mallik,
Biomacromolecules 2016, 17, 2507-2513.
[22] J. Y. Rao, C. Hottinger, A. Khan, J Am Chem Soc 2014, 136, 5872-
5875.
[23] F. Perche, S. Biswas, T. Wang, L. Zhu, V. P. Torchilin, Angew Chem Int
Edit 2014, 53, 3362-3366.
[24] J. Y. Rao, A. Khan, J Am Chem Soc 2013, 135, 14056-14059.
This article is protected by copyright. All rights reserved.

10.1002/chem.201902296
Chemistry - A European Journal
COMMUNICATION
[25] W. Piao, S. Tsuda, Y. Tanaka, S. Maeda, F. Y. Liu, S. Takahashi, Y.
Kushida, T. Komatsu, T. Ueno, T. Terai, T. Nakazawa, M. Uchiyama, K.
Morokuma, T. Nagano, K. Hanaoka, Angew Chem Int Edit 2013, 52,
13028-13032.
[26] K. Kiyose, K. Hanaoka, D. Oushiki, T. Nakamura, M. Kajimura, M.
Suematsu, H. Nishimatsu, T. Yamane, T. Terai, Y. Hirata, T. Nagano, J
Am Chem Soc 2010, 132, 15846-15848.
[27] W. Piao, K. Hanaoka, T. Fujisawa, S. Takeuchi, T. Komatsu, T. Ueno, T.
Terai, T. Tahara, T. Nagano, Y. Urano, J Am Chem Soc 2017, 139,
13713-13719.
[28] J. Li, Y. Yuan, G. S. Zeng, X. Li, Z. Yang, X. Z. Li, R. C. Jiang, W. B. Hu,
P. F. Sun, Q. Wang, X. M. Lu, Q. L. Fan, W. Huang, Polym Chem-Uk
2016, 7, 6890-6894.
[29] S. Y. Lim, K. H. Hong, D. I. Kim, H. Kwon, H. J. Kim, J Am Chem Soc
2014, 136, 7018-7025.
[30] Q. Cai, T. Yu, W. P. Zhu, Y. F. Xu, X. H. Qian, Chem Commun 2015,
51, 14739-14741.
[31] A. Chevalier, P. Y. Renard, A. Romieu, Chem-Asian J 2017, 12, 2008-
2028.
[32] R. B. Wei, X. G. Wang, Y. N. He, Eur Polym J 2015, 69, 584-591.
[33] J. L. Wang, Y. Y. Ouyang, S. Li, X. G. Wang, Y. N. He, Rsc Adv 2016,
6, S7227-S7231.
[34] Y. N. He, W. He, D. Liu, T. H. Gu, R. B. Wei, X. G. Wang, Polym Chem
2013, 4, 402-406.
[35] Y. N. He, W. He, R. B. Wei, Z. Chen, X. G. Wang, Chem Commun
2012, 48, 1036-1038.
[36] J. Rao, A. Khan, Polymer Chemistry 2015, 6, 686-690.
[37] K. Ito, M. Nakanishi, W. C. Lee, Y. Zhi, H. Sasaki, S. Zenno, K. Saigo,
Y. Kitade, M. Tanokura, J Biol Chem 2008, 283, 13889-13896.
[38] A. Ryan, Brit J Pharmacol 2017, 174, 2161-2173.
[39] Y. Yang, Y. Zhang, Q. Y. Wu, X. L. Cui, Z. H. Lin, S. P. Liu, L. Y. Chen,
J Exp Clin Canc Res 2014, 33.
[40] Z. L. Li, Y. Zhang, T. F. Jin, J. G. Men, Z. H. Lin, P. Qi, Y. S. Piao, G. H.
Yan, Bmc Cancer 2015, 15.
[41] A. M. Lewis, M. Ough, M. M. Hinkhouse, M. S. Tsao, L. W. Oberley, J.
J. Cullen, Mol Carcinogen 2005, 43, 215-224.
[42] C. R. Thoma, M. Zimmermann, I. Agarkova, J. M. Kelm, W. Krek, Adv
Drug Deliver Rev 2014, 69, 29-41.
[43] D. V. LaBarbera, B. G. Reid, B. H. Yoo, Expert Opin Drug Dis 2012, 7,
819-830.
[44] S. Daster, N. Amatruda, D. Calabrese, R. Ivanek, E. Turrini, R. A.
Droeser, P. Zajac, C. Fimognari, G. C. Spagnoli, G. Iezzi, V. Mele, M. G.
Muraro, Oncotarget 2017, 8, 1725-1736.
[45] K. Klimkiewicz, K. Weglarczyk, G. Collet, M. Paprocka, A. Guichard, M.
Sarna, A. Jozkowicz, J. Dulak, T. Sarna, C. Grillon, C. Kieda, Cancer
Lett 2017, 396, 10-20.
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Tianhao Xue, Xiangqian Jia, Jilei Wang,
Jingyuan Xiang, Wei Wang, Juanjuan
Du* and Yaning He *
Page No. – Page No.
“
Turn-On” Activatable AIE Dots for
Tumor Hypoxia Imaging
A Novel hypoxia-responsive fluorescence probe of amphiphilic PEGylated azobenzene caged tetraphenylethene for tumor cell
imaging is reported. Besides using UV light, near-infrared (NIR) light can also be used as the excited light resource to generate the
fluorescence due to the two photon fluorescence imaging process.
This article is protected by copyright. All rights reserved.