Co-reporter:Jie Pan, Lijun Jiang, Chi-Fai Chan, Tik-Hung Tsoi, Kwok-Keung Shiu, Daniel W.J. Kwong, Wing-Tak Wong, Wai-Kwok Wong, Ka-Leung Wong
Journal of Luminescence 2017 Volume 184() pp:89-95
Publication Date(Web):April 2017
DOI:10.1016/j.jlumin.2016.12.024
Porphyrins are good photodynamic therapy (PDT) agents due to its flexibility for modifications to achieve tumor localization and photo-cytotoxicity against cancer. Yet they are not perfect. In a Ru(polypyridyl)-porphyrin system, the Ru(polypyridyl) moiety improves the water solubility and cell permeability. Consider the similar excited state energies between Ru(polypyridyl) and porphyrin moieties; a small perturbation (e.g. Zn(II) metalation) would lead to a marked change in the energy migration process. In this work, we have synthesized a series of porphyrins conjugated with Ru(polypyridyl) complexes using different linkers and investigated their photophysical properties, which included singlet oxygen quantum yield and their in vitro biological properties, resulting from linker variation and porphyrin modification by Zn(II) metalation.Four amphiphilic ruthenium(II)-porphyrin complexes were prepared that display energy transfer conversion with zinc coordination, lysosome specific target, low dark toxicity and efficient photodynamic therapy.
Co-reporter:Rui Zou;Junjian Huang;Junpeng Shi;Lin Huang;Xuejie Zhang
Nano Research 2017 Volume 10( Issue 6) pp:2070-2082
Publication Date(Web):27 January 2017
DOI:10.1007/s12274-016-1396-z
Near-infrared (NIR) persistent-luminescence nanoparticles have emerged as a new class of background-free contrast agents that are promising for in vivo imaging. The next key roadblock is to establish a robust and controllable method for synthesizing monodisperse nanoparticles with high luminescence brightness and long persistent duration. Herein, we report a synthesis strategy involving the coating/etching of the SiO2 shell to obtain a new class of small NIR highly persistent luminescent ZnGa2O4:Cr3+,Sn4+ (ZGOCS) nanoparticles. The optimized ZGOCS nanoparticles have an excellent size distribution of ~15 nm without any agglomeration and an NIR persistent luminescence that is enhanced by a factor of 13.5, owing to the key role of the SiO2 shell in preventing nanoparticle agglomeration after annealing. The ZGOCS nanoparticles have a signal-to-noise ratio ~3 times higher than that of previously reported ZnGa2O4:Cr3+ (ZGC-1) nanoparticles as an NIR persistent-luminescence probe for in vivo bioimaging. Moreover, the persistent-luminescence signal from the ZGOCS nanoparticles can be repeatedly re-charged in situ with external excitation by a white lightemitting diode; thus, the nanoparticles are suitable for long-term in vivo imaging applications. Our study suggests an improved strategy for fabricating novel high-performance optical nanoparticles with good biocompatibility.
Co-reporter:Bolong HUANG, Hao DONG, Ka-Leung Wong, Lingdong SUN, Chunhua YAN
Journal of Rare Earths 2017 Volume 35, Issue 4(Volume 35, Issue 4) pp:
Publication Date(Web):1 April 2017
DOI:10.1016/S1002-0721(17)60915-3
To break through the bottle-neck of quantum yield in upconversion (UC) core-shell system, we elucidated that the energy transfer efficiency in core-shell system had an evident contribution from the charge transfer of interface with related to two factors: (1) band offsets and (2) binding energy area density. These two variables were determined by material intrinsic properties and core-shell thickness ratio. We further unraveled the mechanism of non-radiative energy transfer by charge transfer induced dipole at the interface, based on a quasi-classical derivation from Förster type resonant energy transfer (FRET) model. With stable bonding across the interface, the contributions on energy transfer in both radiative and non-radiative energy transfer should also be accounted together in Auzel's energy transfer (ETU) model in core-shell system. Based on the discussion about interface bonding, band offsets, and formation energies, we figured out the significance of interface bonding induced gap states (IBIGS) that played a significant role for influencing the charge transfer and radiative type energy transfer. The interface band offsets were a key factor in dominating the non-radiative energy transfer, which was also correlated to core-shell thickness ratio. We found that the energy area density with related to core/shell thickness ratio followed the trend of Boltzman sigmoidal growth function. By the physical trend, this work contributed a reference how the multi-layered core-shell structure was formed starting from the very beginning within minimum size. A route was paved towards a systematic study of the interface to unveil the energy transfer mechanism in core-shell systems.Left figure estimates thickness relative ratio dependent of valence band offsets (VBO) and conduction band offsets (CBO) for α-NaYF4 and SiO2 layers, with consideration of interface formation energy. Theab-initio DFT calculation shows the interface formation energy area density with related to the variation of shell-to-core thickness ratio (right figure). The results on different surface directions show well-fitted Boltzman function behavior for core-shell growth processDownload high-res image (123KB)Download full-size image
Co-reporter:Sizhe Zhu;Si Yao;Fengshou Wu;Lijun Jiang;Ji Zhou;Kai Wang
Organic & Biomolecular Chemistry 2017 vol. 15(Issue 27) pp:5764-5771
Publication Date(Web):2017/07/12
DOI:10.1039/C7OB01003F
Organelle and nucleus dual-targeted anticancer drugs are being increasingly used for efficient cancer therapy as they can attack the double vital sites of tumor cells. In this work, we synthesized and characterized two new porphyrin compounds Pt-Por-RB and Me-Por-RB. The spectral titration results suggest that both Pt-Por-RB and Me-Por-RB bind to DNA efficiently in an intercalation binding mode. Upon irradiation, Pt-Por-RB with low dark-cytotoxicity can rapidly generate singlet oxygen to damage the tumor cells through the process of photodynamic therapy. Compared with Me-Por-RB, Pt-Por-RB was not only internalized in the organelles, but also in the nuclei of HeLa cells, probably due to the presence of platinum complexes, as analyzed using the confocal laser scanning microscope. Thus, with the combination of organelle and nucleus dual-targeting property and high efficiency of singlet oxygen generation, Pt-Por-RB showed a significant therapeutic activity against tumor cells.
Co-reporter:Hongguang Li;Rongfeng Lan;Chi-Fai Chan;Guochen Bao;Chen Xie;Pak-Ho Chu;William C. S. Tai;Shuai Zha;Jing-Xiang Zhang
Chemical Communications 2017 vol. 53(Issue 52) pp:7084-7087
Publication Date(Web):2017/06/27
DOI:10.1039/C7CC03021E
We report a direct imaging tool, HGEu001, for primary cilia in living cells, which is specific, and based on the UV light or near infrared laser (via two-photon excitation) induced long-lived europium luminescence.
Co-reporter:Jie Pan, Bethany I. Harriss, Chi-Fai Chan, Lijun Jiang, Tik-Hung Tsoi, Nicholas J. Long, Wing-Tak Wong, Wai-Kwok Wong, and Ka-Leung Wong
Inorganic Chemistry 2016 Volume 55(Issue 14) pp:6839-6841
Publication Date(Web):June 29, 2016
DOI:10.1021/acs.inorgchem.6b01159
A water-soluble bimetallic normal (“cold”) and radiochemical (“hot”) gallium–porphyrin–ruthenium–bipyridine complex (GaporRu-1) has been synthesized by microwave methodology in short reaction times with good (>85%) yields. 68GaporRu-1 is demonstrated to be a potential multimodal and functional bioprobe for positron emission tomography (PET), lysosome specific optical imaging, and photodynamic therapy.
Co-reporter:Wai-Sum Lo, Hongguang Li, Ga-Lai Law, Wing-Tak Wong, Ka-Leung Wong
Journal of Luminescence 2016 Volume 169(Part B) pp:549-552
Publication Date(Web):January 2016
DOI:10.1016/j.jlumin.2014.12.051
•A turn-on NIR-emissive 1O2 probe has been synthesized for potential biological applications.•It has a binding constant of 1.9×106 M−1 and the emission intensity has a 5-fold increase upon binding.•The probe was also found to quench singlet oxygen in vitro generated by known photosensitizer TMPyP.A responsive neodymium NIR emission (4F3/2→4I11/2, 9/2) was recorded upon binding with singlet oxygen (KB=1.79×106 M−1) via the anthracene moiety. The motif ytterbium analog served as a negative control with no significant NIR enhancement/quenching with the addition of the same amount of singlet oxygen. Our complex was also found to react with 1O2 generated by a known photosensitizer TMPyP inside HeLa cells without inducing cell death and display no significant cytotoxicity.
Co-reporter:Tao Zhang, Baoyan Wu, Zhengzhi Zou, Yunxia Wu, Judun Zheng, Wai-Kwok Wong, Ka-Leung Wong
Journal of Luminescence 2016 Volume 170(Part 1) pp:187-193
Publication Date(Web):February 2016
DOI:10.1016/j.jlumin.2015.10.037
A new rhodamine-based fluorescent probe based on the known ring-opening mechanism of rhodamine derivative, was successfully synthesized and demonstrated to detect the Hg2+ with high selectivity and sensitivity in aqueous solution and living cells. In the presence of Hg2+, the probe exhibit remarkably amplified absorption with a binding constant determined as 8.76±0.13, followed by a distinct change in color and 560-fold enhancement of fluorescence with a reversible response and little interference with other biological relevant metal ions. Moreover, the confocal microscopic switch-on imaging in MCF-7 cells of the probe towards Hg2+, together with its non-cytotoxicity and efficient cellular uptake, confirmed that the probe can be used as a biocompatible probe for monitoring of Hg2+ in living cells.
Co-reporter:Bolong Huang, Hao Dong, Ka-Leung Wong, Ling-Dong Sun, and Chun-Hua Yan
The Journal of Physical Chemistry C 2016 Volume 120(Issue 33) pp:18858-18870
Publication Date(Web):August 8, 2016
DOI:10.1021/acs.jpcc.6b05261
We discussed the electronic structures of β-NaLnF4 (Ln = Y, Gd, and Lu). We found the band gap keeps nearly constant (8–9 eV). However, the difference of the experimentally observed band gap arises from the different positions of 4f orbital levels relative to the valence band maximum. The 4f empty state of Gd falls into the band gap, led to a decreased band gap for β-NaGdF4, and is spin-polarized. In contrast, both filled and empty 4f levels of Lu widely separated below and above the valence and conduction band edges, respectively, which means they do not influence the optical transitions in the band gap of the host lattice. By projecting the components of self-energy and wave function relaxation in 4f orbitals, we indicated a hidden level of Gd and Lu ions in the β-lattices, giving three Gd/Lu ions in the lattice split into two different types of electronic levels. This analysis helped us understand the essential mechanism and modified the energy migration mediated upconversion (EMU) model. Different 4f levels of Gd ions have been updated. This reason may arise from different charge density overlaps of local F–Ln (Ln = Y, Gd, and Lu), given by 2p and 4d/4f orbitals, respectively. We thus discussed that the local disorder of fluoride modulates the electronic eigenvalues of the top of the valence band near the Γ point within the first Brillouin zone (BZ). The conduction band minimum is always located at the Γ point consisting of the d orbitals of Y/Gd/Lu, regardless of the site occupation disorder effect between Y/Gd/Lu and Na. One of the lattices possesses a direct band gap indicating a route to increase the efficiency of the vertical optical transition along the Γ direction. This work proposed a convenient route for future investigation of the interface states that potentially quench the upconversion luminescence.
Co-reporter:Joan Goetz;Dr. Aline Nonat;Abdoulaye Diallo;Mohamadou Sy;Ildan Sera;Alexre Lecointre;Dr. Christophe Lefevre;Chi Fai Chan;Dr. Ka-Leung Wong;Dr. Loïc J. Charbonnière
ChemPlusChem 2016 Volume 81( Issue 6) pp:526-534
Publication Date(Web):
DOI:10.1002/cplu.201600007
Abstract
Tb-doped La0.9Tb0.1F3 nanoparticles were prepared by a simple and reproducible microwave-assisted synthetic protocol in water. The nanoparticles were characterized by XRD, TEM, dynamic light scattering and inductively coupled plasma atomic emission spectroscopy elemental analysis. Eleven ligands with varying coordination and photosensitizing abilities were designed to bind at the surface of the Tb-doped nanoparticles. The photosensitizing behavior was monitored by electronic absorption spectroscopy and steady-state and time-resolved emission spectroscopy. The two most effective photosensitizing ligands were used to isolate and purify the capped nanoparticles. The composition and spectroscopic properties of these nanoparticles were measured, which revealed either 2660 and 5240 ligands per nanoparticle, molar absorptivities of 7.6×106 and 1.6×107 m−1 cm−1 and luminescence quantum yields of 0.29 and 0.13 in water, respectively. These data correspond to exceptional brightness values of 2.2×106 and 2.1×106 m−1 cm−1, respectively. The as-prepared nanoparticles were imaged in HeLa cells by fluorescence microscopy, which showed their specific localization in lysosomes.
Co-reporter:Joan Goetz;Dr. Aline Nonat;Abdoulaye Diallo;Mohamadou Sy;Ildan Sera;Alexre Lecointre;Dr. Christophe Lefevre;Chi Fai Chan;Dr. Ka-Leung Wong;Dr. Loïc J. Charbonnière
ChemPlusChem 2016 Volume 81( Issue 6) pp:
Publication Date(Web):
DOI:10.1002/cplu.201600117
Abstract
Invited for this month's cover are the collaborating groups of Dr. Loïc J. Charbonnière at CNRS/Université de Strasbourg, France and Dr. Ka-Leung Wong at Hong Kong Baptist University, Hong Kong. The cover picture shows terbium-doped LaF3 nanoparticles that are surface functionalized by photon-harvesting antenna ligands. Surface capping with antenna ligands leads to ultrabright nanoparticles, with the typical green luminescence signature of the Tb atoms and very long excited-state lifetimes. These lanthanide dots can be incorporated into living cells at nanomolar concentrations for luminescence microscopy imaging. Read the full text of the article at 10.1002/cplu.201600007.
Co-reporter:Joan Goetz;Dr. Aline Nonat;Abdoulaye Diallo;Mohamadou Sy;Ildan Sera;Alexre Lecointre;Dr. Christophe Lefevre;Chi Fai Chan;Dr. Ka-Leung Wong;Dr. Loïc J. Charbonnière
ChemPlusChem 2016 Volume 81( Issue 6) pp:
Publication Date(Web):
DOI:10.1002/cplu.201600116
Co-reporter:Bo Wei, Zhenyu Liu, Chen Xie, Shu Yang, Wentao Tang, Aiwei Gu, Wing-Tak Wong and Ka-Leung Wong
Journal of Materials Chemistry A 2015 vol. 3(Issue 47) pp:12322-12327
Publication Date(Web):13 Nov 2015
DOI:10.1039/C5TC03165F
Red Li3BaSrLa3(WO4)8:Eu3+ phosphors have been successfully synthesized by a rapid microwave-assisted solid state method. The sintering time for the optimal phosphor can be limited to only 10 minutes at 900 °C. Upon near-ultra-violet (NUV) excitation, strong red emission can be found in 90% Eu3+ doped tungstate compounds. This phosphor exhibits impressive thermal stability, and the purity of red emission Li3BaSrLa3(WO4)8:Eu3+ in high Eu3+ doping concentrations can achieve the coordinate values (x = 0.670, y = 0.330), indicating high red color purity. The corresponding quantum yield (QY) is measured (28.36 ± 0.09%). Photoluminescence and kinetic studies showed no obvious effects due to the concentration quenching effect, cross relaxation and non-radiative energy transfer. Li3BaSrLa3(WO4)8:Eu3+ can be synthesized using a simple and quick method and the comprehensive photophysical studies of the novel phosphor (Li3BaSrLa3(WO4)8:Eu3+) have been done and the potential as a practical phosphor for NUV-excited white LEDs (WLEDs) has been shown.
Co-reporter:Wai-Lun Chan, Zhenyu Liu, Shengbo Lu, Peter A. Tanner and Ka-Leung Wong
Journal of Materials Chemistry A 2015 vol. 3(Issue 5) pp:960-963
Publication Date(Web):19 Dec 2014
DOI:10.1039/C4TC02490G
The assigned anomalous upconversion emission intensity of the 5D0 → 7F4 transition of Eu3+ in the double perovskite Sr2Ca(W1−xMox)O6 co-doped with Yb3+ is shown to be due to a transition metal impurity present in the MoO3 starting material. Relevant literature shows that the highest energy 5D0 → 7F4 transition is at a longer wavelength than 685 nm in molybdates. Cases of anomalous intensity of this transition are reviewed. Our 360 nm excited emission spectra of Sr2Ca0.88Eu0.02Yb0.04Li0.06MoO6 show a very weak 5D0 → 7F4 transition, but on co-doping with Mn a structured band between 640 and 710 nm is observed due to Mn4+.
Co-reporter:Chi-Fai Chan, Rongfeng Lan, Ming-Kiu Tsang, Di Zhou, Sam Lear, Wai-Lun Chan, Steven L. Cobb, Wai-Kwok Wong, Jianhua Hao, Wing-Tak Wong and Ka-Leung Wong
Journal of Materials Chemistry A 2015 vol. 3(Issue 13) pp:2624-2634
Publication Date(Web):05 Feb 2015
DOI:10.1039/C4TB02104E
Polo-like kinase 1 (Plk1) is a major serine/threonine protein kinase which regulates key mitotic events such as centrosome duplication, spindle assembly and chromosome separation. Overexpression and aberrant activities of Plk1 can be detected in different types of cancer. Given that the unique polo box domain (PBD) pocket provides an excellent drug target for Plk1 binding and inhibition, we have rationally designed multifunctional lanthanide-doped upconversion nanomaterials. NaGdF4:Yb3+, Er3+ (NaGdF4) and BaGdF5:Yb3+, Er3+ (BaGdF5) nanoparticles of two different sizes (60 nm and 10 nm, respectively) have been thin-coated with Plk1 specific peptides (–P1 = PLHSpT, –P2 = PLHSD, and –P3 = GGPLHSpT) to prepare novel nanomaterials. Comparative studies on cellular uptake, anti-cancer activity and imaging properties were then carried out. The experimental data obtained support our original hypothesis that the designed nanomaterials can successfully deliver Plk1 specific peptides into cancer cells causing Plk1 inhibition while simultaneously allowing direct NIR imaging and monitoring. Among the NaGdF4–Pn and BaGdF5–Pn nanoparticle series prepared in this study, NaGdF4–P1 emerged as the best candidate for Plk1 binding and imaging. NaGdF4–P1 can effectively exert cell cycle G2/M arrest and thus selective tumor inhibition both in vitro and in vivo and as such it offers a potentially interesting system for the development of new cancer therapies.
Co-reporter:Hongguang Li, Rongfeng Lan, Chi-Fai Chan, Lijun Jiang, Lixiong Dai, Daniel W. J. Kwong, Michael Hon-Wah Lam and Ka-Leung Wong
Chemical Communications 2015 vol. 51(Issue 74) pp:14022-14025
Publication Date(Web):30 Jul 2015
DOI:10.1039/C5CC05461C
A water-soluble light-responsive antitumor agent, PtEuL, based on a cisplatin-linked europium–cyclen complex has been synthesized and evaluated for controlled cisplatin release by linear/two-photon excitation in vitro with concomitant turn-on and long-lived europium emission as a responsive traceable signal.
Co-reporter:Zhenhao Liang, Chi-Fai Chan, Yurong Liu, Wing-Tak Wong, Chi-Sing Lee, Ga-Lai Law and Ka-Leung Wong
RSC Advances 2015 vol. 5(Issue 18) pp:13347-13356
Publication Date(Web):13 Jan 2015
DOI:10.1039/C4RA16536E
Five water-soluble cyclen-based europium complexes incorporated with the pendant chelating chromophore, 2-methyl-4-(2-(4-propoxyphenyl)ethynyl)pyridine (L), as the antenna in different ratios have been synthesized and full structural characterization, photophysical measurement and in vitro biological studies were carried out. The antenna-to-metal ratios were 4 (Eu-4L), 3 (Eu-3L), 2 (1,4-disubstituted Eu-o-2L and 1,7-disubstituted Eu-p-2L) and 1 (Eu-1L). It was found that the definitive distinction between Eu-o-2L and Eu-p-2L could be interpreted from the emission spectra of Eu3+ at room and low temperatures. With all the results from subcellular stability testing (via titrations), in vitro imaging, cytotoxicity assays and cellular uptake profiles, Eu-4L with an overall +3 charge demonstrated subcellular localization towards lysosomes and was a potential compound for a selective time-resolved bio-labelling probe.
Co-reporter:Chi-Fai Chan, Ming-Kiu Tsang, Hongguang Li, Rongfeng Lan, Frances L. Chadbourne, Wai-Lun Chan, Ga-Lai Law, Steven L. Cobb, Jianhua Hao, Wing-Tak Wong and Ka-Leung Wong
Journal of Materials Chemistry A 2014 vol. 2(Issue 1) pp:84-91
Publication Date(Web):18 Nov 2013
DOI:10.1039/C3TB21034K
Inhibition of the CDK4/cyclin D complex through the substrate recruitment site on the cyclin positive regulatory subunit is recognised as being a promising anti-cancer target. Specific peptide sequences can be used to selectively disrupt this target, but the development of peptides as anti-tumor agents in vitro/in vivo presents several obstacles. Poor cell internalization, low sensitivity towards enzymatic degradation in vivo, and ineffectiveness in monitoring via indirect screening are all issues which must be overcome. Herein, we describe the surface functionalization of lanthanide nanoparticles with cyclin D-specific peptides to prepare novel nanomaterials (UCNPs–P1) which can target the CDK4/cyclin D complex. The nanomaterials prepared (UCNPs–P1) are cell permeable and they display parallel emission spectra in vitro and in an aqueous biological environment. They can also be used in low dose concentrations under harmless NIR excitation and emission via upconversion. Uniquely, in addition to acting as a bioimaging probe, UCNPs–P1 also exhibits promising cytotoxicity towards cancer cells. In light of the aforementioned properties, the prepared functionalized nanomaterials (UCNPs–P1) offer the first real dual acting system for cyclin D imaging and simultaneous inhibition of cancer cell division.
Co-reporter:Lijun Jiang, Yin-Lai Lui, Hongguang Li, Chi-Fai Chan, Rongfeng Lan, Wai-Lun Chan, Terrence Chi-Kong Lau, George Sai-Wah Tsao, Nak-Ki Mak and Ka-Leung Wong
Chemical Communications 2014 vol. 50(Issue 49) pp:6517-6519
Publication Date(Web):28 Mar 2014
DOI:10.1039/C4CC01589D
An EBNA1-specific small molecule (JLP2) has been synthesised. As a strong binder and dimerization inhibitor of EBNA1 in vitro, JLP2 may be used as a selective luminescent agent for the imaging and inhibition of latent EBV-infected cancer cells.
Co-reporter:Hongguang Li, Chi-Fai Chan, Wai-Lun Chan, Sam Lear, Steven L. Cobb, Nai-Ki Mak, Terrence Chi-Kong Lau, Rongfeng Lan, Wai-Kwok Wong and Ka-Leung Wong
Organic & Biomolecular Chemistry 2014 vol. 12(Issue 31) pp:5876-5882
Publication Date(Web):18 Jun 2014
DOI:10.1039/C4OB00853G
Polo-like kinase 1 (Plk1) is well-known for taking part in cell cycle progression and regulation. Using small molecules for Plk inhibition has been well documented in the literature. However, there are several intrinsic and intractable problems associated with this approach. For example monitoring small molecule Plk inhibitors as anti-tumor agents in vitro/in vivo is often ineffective, they can have poor cell internalization and be susceptible to enzymatic degradation. Herein, we report the synthesis of cell-permeable, water-soluble amphiphilic porphyrin – Plk1 specific peptide bioconjugates, Por-P1 and Por-P2. In addition to resolving the aforementioned problems of the small molecule inhibitors Por-P2 manifests responsive emission enhancement upon binding with Plk1 in aqueous medium and in vitro, while potently triggering G2-M phase arrest and then apoptosis selectively in the cancer cells tested. In combination our findings make Por-P2 a promising candidate for the preparation of a new generation of smart chemotherapeutic targeting agents (imaging and inhibition) for Plk1 in particular cancer cell lines.
Co-reporter:Dr. Tao Zhang;Chi-Fai Chan;Dr. Rongfeng Lan; Wai-Kwok Wong;Dr. Ka-Leung Wong
Chemistry - A European Journal 2014 Volume 20( Issue 4) pp:970-973
Publication Date(Web):
DOI:10.1002/chem.201303863
Abstract
A new lanthanide probe based on the fluorescence resonance energy transfer (FRET) process with the combination of ytterbium porphyrinate complex and a rhodamine B derivative unit was synthesized to detect the Hg2+ ion with responsive emission in the visible and near-IR region with a detection limit of 10 μM
Co-reporter:Tao Zhang;Rongfeng Lan;Chi-Fai Chan;Ga-Lai Law;Wai-Kwok Wong
PNAS 2014 Volume 111 (Issue 51 ) pp:E5492-E5497
Publication Date(Web):2014-12-23
DOI:10.1073/pnas.1414499111
In this work, we demonstrate a modality of photodynamic therapy (PDT) through the design of our truly dual-functional—PDT
and imaging—gadolinium complex (Gd-N), which can target cancer cells specifically. In the light of our design, the PDT drug
can specifically localize on the anionic cell membrane of cancer cells in which its laser-excited photoemission signal can
be monitored without triggering the phototoxic generation of reactive oxygen species—singlet oxygen—before due excitation.
Comprehensive in vitro and in vivo studies had been conducted for the substantiation of the effectiveness of Gd-N as such
a tumor-selective PDT photosensitizer. This treatment modality does initiate a new direction in the development of “precision
medicine” in line with stem cell and gene therapies as tools in cancer therapy.
Co-reporter:Tao Zhang, Chi-Fai Chan, Rongfeng Lan, Hongguang Li, Nak-Ki Mak, Wai-Kwok Wong and Ka-Leung Wong
Chemical Communications 2013 vol. 49(Issue 65) pp:7252-7254
Publication Date(Web):24 Jun 2013
DOI:10.1039/C3CC43469A
A porphyrin ytterbium complex (Yb-N) showed strong binding to phosphatidylserine and capability to differentiate cancer cells via targeting the anionic phospholipid membrane.
Co-reporter:Hongguang Li, Frances L. Chadbourne, Rongfeng Lan, Chi-Fai Chan, Wai-Lun Chan, Ga-Lai Law, Chi-Sing Lee, Steven L. Cobb and Ka-Leung Wong
Dalton Transactions 2013 vol. 42(Issue 37) pp:13495-13501
Publication Date(Web):08 Jul 2013
DOI:10.1039/C3DT51053K
Six water-soluble europium complexes (Eu–L11–Pnnn and Eu–L22–Pnnn, n = 1, 2 and 3) with one antenna chromophore, two different linkers (L11 and L22) and three proposed cyclin A specific peptides (P11: -GAKRRLIF-NH2; P22: -GGAKRRLIF-NH2; P33: -Hex- GAKRRLIF-NH2) have been synthesized. With structural information available, comparisons of the cyclin grooves of cyclin A and the six europium complexes have been made, and insights have been gained into the determinants for peptide binding and the foundation of differential binding. Experiment-wise, the linear and two-photon induced photophysical properties of these conjugates were monitored in aqueous solution. Numerous in situ/in vitro biological assays have been carried out, such as responsive emission changes in situ/in vitro, Western blot and cellular uptake. As imaging agents, complexes with peptides P33: -Hex-GAKRRLIF-NH2 showed high selectivity to cyclin A in numerous cancer cells. When it comes to responsive optical signal changes, complex Eu–L22–P33 exhibited a threefold emission enhancement upon binding with cyclin A (100 nM cyclin A, ϕ = 8% to 21%, log KB = 5.83, detection limit = 5 nM), and this could be initiated by the shortened distance between the antenna and the lanthanide after they bind/get into cyclin A. It is promising that our compounds (especially compound Eu–L22–P33) could serve as the template for structure-guided efforts to develop potential imaging therapeutics on the basis of selective imaging of CDK2/cyclin A activity.
Co-reporter:Tao Zhang, Chi-Fai Chan, JianHua Hao, Ga-Lai Law, Wai-Kwok Wong and Ka-Leung Wong
RSC Advances 2013 vol. 3(Issue 2) pp:382-385
Publication Date(Web):13 Nov 2012
DOI:10.1039/C2RA22056C
A water-soluble, mitochondria-permeable erbium(III) complex has been designed as a responsive bi-functional probe. This may be used to induce the mild formation of singlet oxygen (ΦΔ = 0.10) and causes local damage in cellulo when exposed to UV and near-infrared laser excitation.
Co-reporter:Jing-Xiang Zhang, Hongguang Li, Chi-Fai Chan, Rongfeng Lan, Wai-Lun Chan, Ga-Lai Law, Wai-Kwok Wong and Ka-Leung Wong
Chemical Communications 2012 vol. 48(Issue 77) pp:9646-9648
Publication Date(Web):09 Aug 2012
DOI:10.1039/C2CC34963A
An amphiphilic water-soluble ytterbium complex which is photo-selective, functional and Golgi apparatus specific has been designed as a responsive dual probe capable of sensitizing emission within the biological window (660 and 750 nm), generating the singlet oxygen (ΦΔ = 0.45) and triggering local cell damage only upon exposure to visible and near-infrared laser excitation.
Co-reporter:Yuk-Wang Yip, Hongli Wen, Wing-Tak Wong, Peter A. Tanner, and Ka-Leung Wong
Inorganic Chemistry 2012 Volume 51(Issue 13) pp:7013-7015
Publication Date(Web):June 19, 2012
DOI:10.1021/ic300916e
Three europium complexes with the terdentate N-donor ligand 2,6-bis(1H-pyrazol-3-yl)pyridine (L) have been synthesized, and their crystal structures have been determined. The ligand/metal ratios in these complexes are 3, 2, and 1. The photophysical properties of the complexes indicate more efficient ligand sensitization of europium emission for the homoleptic complex.
Co-reporter:Jing-Xiang Zhang, Jun-Wei Zhou, Chi-Fai Chan, Terrence Chi-Kong Lau, Daniel W. J. Kwong, Hoi-Lam Tam, Nai-Ki Mak, Ka-Leung Wong, and Wai-Kwok Wong
Bioconjugate Chemistry 2012 Volume 23(Issue 8) pp:1623
Publication Date(Web):July 9, 2012
DOI:10.1021/bc300201h
Six water-soluble free-base porphyrin-Ru(II) conjugates, 1–3, and Zn(II) porphyrin-Ru(II) conjugates, 4–6, with different linkers between the hydrophobic porphyrin moiety and the hydrophilic Ru(II)-polypyridyl complex, have been synthesized. The linear and two-photon-induced photophysical properties of these conjugates were measured and evaluated for their potential application as dual in vitro imaging and photodynamic therapeutic (PDT) agents. Conjugates 1–3, with their high luminescence and singlet oxygen quantum yields, were selected for further study of their cellular uptake, subcellular localization, and cytotoxic and photocytotoxic (under linear and two-photon excitation) properties using HeLa cells. Conjugate 2, with its hydrophobic phenylethynyl linker, was shown to be highly promising for further development as a bifunctional probe for two-photon (NIR) induced PDT and in vitro imaging. Cellular uptake and subcellular localization properties were shown to be crucial to its PDT efficacy.
Co-reporter:Tao Zhang ; Xunjin Zhu ; Chopen C. W. Cheng ; Wai-Ming Kwok ; Hoi-Lam Tam ; Jianhua Hao ; Daniel W. J. Kwong ; Wai-Kwok Wong
Journal of the American Chemical Society 2011 Volume 133(Issue 50) pp:20120-20122
Publication Date(Web):November 21, 2011
DOI:10.1021/ja207689k
A water-soluble porphyrinato ytterbium complex linked with rhodamine B (Yb-2) showed mitochondria-specific subcellular localization and strong two-photon-induced NIR emissions (λem = 650 nm, porphyrinate ligand π → π* transition; λem = 1060 nm, Yb(III) 5F5/2 → 5F7/2 transitions; σ2 = 375 GM in DMSO) with an impressive Yb(III) NIR emission quantum yield (1% at λex = 340 nm; 2.5% at λex = 430 nm) in aqueous solution.
Co-reporter:Hoi-Kwan Kong, Frances L Chadbourne, Ga-Lai Law, Hongguang Li, Hoi-Lam Tam, Steven L Cobb, Chi-Kong Lau, Chi-Sing Lee and Ka-Leung Wong
Chemical Communications 2011 vol. 47(Issue 28) pp:8052-8054
Publication Date(Web):16 Jun 2011
DOI:10.1039/C1CC12811F
Responsive linear and two-photon induced europium emissive probes have been synthesised with a tailor made peptide for the detection of Cyclin A, the hypersensitive Eu emission (Eu-2) gave the real time signalling and also enhanced the two-photon absorption cross section from 12 GM to 68 GM after Cyclin A binding.
Co-reporter:Wai-Sum Lo ; Wai-Ming Kwok ; Ga-Lai Law ; Chi-Tung Yeung ; Chris Tsz-Leung Chan ; Ho-Lun Yeung ; Hoi-Kuan Kong ; Chi-Hang Chen ; Margaret B. Murphy ; Ka-Leung Wong ;Wing-Tak Wong
Inorganic Chemistry 2011 Volume 50(Issue 12) pp:5309-5311
Publication Date(Web):May 16, 2011
DOI:10.1021/ic102465j
Three triazine-based europium(III) complexes were synthesized that demonstrated strong two-photon induced europium emission with a high two-photon absorption cross-section. The modified triazine ligand of complex 3 initiated over 100% enhancement of the two-photon absorption cross-section (σ2: 320 GM) when compared with complex 1 (σ2: 128 GM) in a solution of DMSO. Europium complex 3 is also stable in vitro, and power-dependence curves were obtained in vitro to confirm the two-photon-induced f–f emission in HeLa cells.
Co-reporter:JingXiang Zhang, Ka-Leung Wong, Wai-Kwok Wong, Nai-Ki Mak, Daniel W. J. Kwong and Hoi-Lam Tam
Organic & Biomolecular Chemistry 2011 vol. 9(Issue 17) pp:6004-6010
Publication Date(Web):12 Jul 2011
DOI:10.1039/C1OB05415E
Two Ru(II) polypyridyl-porphyrin and Zn(II) porphyrin conjugates (Ru-L and Ru-Zn-L) have been synthesized and their photophysical properties studied. The two conjugates, which contained a hydrophobic tetraphenylporphyrin L conjugated via an acetylide linker at its β-position with a hydrophilic Ru(II) polypyridyl complex, showed high singlet oxygen quantum yields (>70%) and substantial two-photon absorption cross-sections (∼500 GM). Ru-L gave strong emissions at ∼660 and ∼733 nm through linear or two-photon excitation. Solvatochromism was observed in the fluorescence spectra of Ru-L and Ru-Zn-L, where in less polar solvents (i.e., toluene and dichloromethane) their fluorescence emissions became slightly blue-shifted with a 3-fold reduction in intensity relative to those observed in polar solvents (i.e., acetonitrile and methanol). Cell-based studies of these complex conjugates were conducted using human nasopharyngeal carcinoma HK-1 and cervical carcinoma HeLa cells on which Ru-L showed rapid cellular uptake, low dark-cytotoxicity, and high photo-cytotoxicity. Furthermore, Ru-L can be excited and emits in the “biological window” in vitro, making it a potential potent new generation photodynamic therapeutic agent capable of singlet oxygen generation and in vitro near-infrared emission.
Co-reporter:Wanqing Wu;Hoi-Kuan Kong;Hongguang Li;Yu-Man Ho;Yuan Gao;Jianhua Hao;Margaret B. Murphy;Michael Hon-Wah Lam;Chi-Sing Lee
European Journal of Organic Chemistry 2011 Volume 2011( Issue 26) pp:5054-5060
Publication Date(Web):
DOI:10.1002/ejoc.201100570
Abstract
A new class of organic molecular probes (1–3) based on a 1,3-disubstituted diethynylbenzene core has been developed. Both 1 and 2 (with the esters of 1 replaced by diethylamides in 2) show good linear and three-photon induced photophysical properties with two-photon absorption cross-sections (185–210 cm4 s photon–1 molecule–1) that are suitable for biological applications in live specimens. The propeller π-conjugated systems of 3 (a C3 analogue of 1) shows threefold enhancement for the two-photon absorption cross-section (650 cm4 s photon–1 molecule–1). Solvatochromism was observed in the fluorescence spectra of all these molecular probes; in acidic medium (pH = 4–5) their fluorescence emissions are slightly blueshifted with a threefold enhancement in intensity relative to those observed under basic conditions (pH = 10–11). In the fluorometric titration study against a variety of bioactive small molecules, only 2 shows strong binding affinity (log KB > 7) towards citrates and bicarbonates with approximately 30 nm redshift. The in vitro emission spectra of 2 obtained show the same emission upon addition of anions to the solution. The results of these studies could provide new molecular-design strategies for two-photo absorption (TPA) chromophores and new materials for two/multi-photon imaging in vitro.
Co-reporter:Hongguang Li, Rongfeng Lan, Chi-Fai Chan, Lijun Jiang, Lixiong Dai, Daniel W. J. Kwong, Michael Hon-Wah Lam and Ka-Leung Wong
Chemical Communications 2015 - vol. 51(Issue 74) pp:NaN14025-14025
Publication Date(Web):2015/07/30
DOI:10.1039/C5CC05461C
A water-soluble light-responsive antitumor agent, PtEuL, based on a cisplatin-linked europium–cyclen complex has been synthesized and evaluated for controlled cisplatin release by linear/two-photon excitation in vitro with concomitant turn-on and long-lived europium emission as a responsive traceable signal.
Co-reporter:Lijun Jiang, Yin-Lai Lui, Hongguang Li, Chi-Fai Chan, Rongfeng Lan, Wai-Lun Chan, Terrence Chi-Kong Lau, George Sai-Wah Tsao, Nak-Ki Mak and Ka-Leung Wong
Chemical Communications 2014 - vol. 50(Issue 49) pp:NaN6519-6519
Publication Date(Web):2014/03/28
DOI:10.1039/C4CC01589D
An EBNA1-specific small molecule (JLP2) has been synthesised. As a strong binder and dimerization inhibitor of EBNA1 in vitro, JLP2 may be used as a selective luminescent agent for the imaging and inhibition of latent EBV-infected cancer cells.
Co-reporter:Tao Zhang, Chi-Fai Chan, Rongfeng Lan, Hongguang Li, Nak-Ki Mak, Wai-Kwok Wong and Ka-Leung Wong
Chemical Communications 2013 - vol. 49(Issue 65) pp:NaN7254-7254
Publication Date(Web):2013/06/24
DOI:10.1039/C3CC43469A
A porphyrin ytterbium complex (Yb-N) showed strong binding to phosphatidylserine and capability to differentiate cancer cells via targeting the anionic phospholipid membrane.
Co-reporter:Hoi-Kwan Kong, Frances L Chadbourne, Ga-Lai Law, Hongguang Li, Hoi-Lam Tam, Steven L Cobb, Chi-Kong Lau, Chi-Sing Lee and Ka-Leung Wong
Chemical Communications 2011 - vol. 47(Issue 28) pp:NaN8054-8054
Publication Date(Web):2011/06/16
DOI:10.1039/C1CC12811F
Responsive linear and two-photon induced europium emissive probes have been synthesised with a tailor made peptide for the detection of Cyclin A, the hypersensitive Eu emission (Eu-2) gave the real time signalling and also enhanced the two-photon absorption cross section from 12 GM to 68 GM after Cyclin A binding.
Co-reporter:Jing-Xiang Zhang, Hongguang Li, Chi-Fai Chan, Rongfeng Lan, Wai-Lun Chan, Ga-Lai Law, Wai-Kwok Wong and Ka-Leung Wong
Chemical Communications 2012 - vol. 48(Issue 77) pp:NaN9648-9648
Publication Date(Web):2012/08/09
DOI:10.1039/C2CC34963A
An amphiphilic water-soluble ytterbium complex which is photo-selective, functional and Golgi apparatus specific has been designed as a responsive dual probe capable of sensitizing emission within the biological window (660 and 750 nm), generating the singlet oxygen (ΦΔ = 0.45) and triggering local cell damage only upon exposure to visible and near-infrared laser excitation.
Co-reporter:Hongguang Li, Chi-Fai Chan, Wai-Lun Chan, Sam Lear, Steven L. Cobb, Nai-Ki Mak, Terrence Chi-Kong Lau, Rongfeng Lan, Wai-Kwok Wong and Ka-Leung Wong
Organic & Biomolecular Chemistry 2014 - vol. 12(Issue 31) pp:NaN5882-5882
Publication Date(Web):2014/06/18
DOI:10.1039/C4OB00853G
Polo-like kinase 1 (Plk1) is well-known for taking part in cell cycle progression and regulation. Using small molecules for Plk inhibition has been well documented in the literature. However, there are several intrinsic and intractable problems associated with this approach. For example monitoring small molecule Plk inhibitors as anti-tumor agents in vitro/in vivo is often ineffective, they can have poor cell internalization and be susceptible to enzymatic degradation. Herein, we report the synthesis of cell-permeable, water-soluble amphiphilic porphyrin – Plk1 specific peptide bioconjugates, Por-P1 and Por-P2. In addition to resolving the aforementioned problems of the small molecule inhibitors Por-P2 manifests responsive emission enhancement upon binding with Plk1 in aqueous medium and in vitro, while potently triggering G2-M phase arrest and then apoptosis selectively in the cancer cells tested. In combination our findings make Por-P2 a promising candidate for the preparation of a new generation of smart chemotherapeutic targeting agents (imaging and inhibition) for Plk1 in particular cancer cell lines.
Co-reporter:JingXiang Zhang, Ka-Leung Wong, Wai-Kwok Wong, Nai-Ki Mak, Daniel W. J. Kwong and Hoi-Lam Tam
Organic & Biomolecular Chemistry 2011 - vol. 9(Issue 17) pp:NaN6010-6010
Publication Date(Web):2011/07/12
DOI:10.1039/C1OB05415E
Two Ru(II) polypyridyl-porphyrin and Zn(II) porphyrin conjugates (Ru-L and Ru-Zn-L) have been synthesized and their photophysical properties studied. The two conjugates, which contained a hydrophobic tetraphenylporphyrin L conjugated via an acetylide linker at its β-position with a hydrophilic Ru(II) polypyridyl complex, showed high singlet oxygen quantum yields (>70%) and substantial two-photon absorption cross-sections (∼500 GM). Ru-L gave strong emissions at ∼660 and ∼733 nm through linear or two-photon excitation. Solvatochromism was observed in the fluorescence spectra of Ru-L and Ru-Zn-L, where in less polar solvents (i.e., toluene and dichloromethane) their fluorescence emissions became slightly blue-shifted with a 3-fold reduction in intensity relative to those observed in polar solvents (i.e., acetonitrile and methanol). Cell-based studies of these complex conjugates were conducted using human nasopharyngeal carcinoma HK-1 and cervical carcinoma HeLa cells on which Ru-L showed rapid cellular uptake, low dark-cytotoxicity, and high photo-cytotoxicity. Furthermore, Ru-L can be excited and emits in the “biological window” in vitro, making it a potential potent new generation photodynamic therapeutic agent capable of singlet oxygen generation and in vitro near-infrared emission.
Co-reporter:Wai-Lun Chan, Zhenyu Liu, Shengbo Lu, Peter A. Tanner and Ka-Leung Wong
Journal of Materials Chemistry A 2015 - vol. 3(Issue 5) pp:NaN963-963
Publication Date(Web):2014/12/19
DOI:10.1039/C4TC02490G
The assigned anomalous upconversion emission intensity of the 5D0 → 7F4 transition of Eu3+ in the double perovskite Sr2Ca(W1−xMox)O6 co-doped with Yb3+ is shown to be due to a transition metal impurity present in the MoO3 starting material. Relevant literature shows that the highest energy 5D0 → 7F4 transition is at a longer wavelength than 685 nm in molybdates. Cases of anomalous intensity of this transition are reviewed. Our 360 nm excited emission spectra of Sr2Ca0.88Eu0.02Yb0.04Li0.06MoO6 show a very weak 5D0 → 7F4 transition, but on co-doping with Mn a structured band between 640 and 710 nm is observed due to Mn4+.
Co-reporter:Bo Wei, Zhenyu Liu, Chen Xie, Shu Yang, Wentao Tang, Aiwei Gu, Wing-Tak Wong and Ka-Leung Wong
Journal of Materials Chemistry A 2015 - vol. 3(Issue 47) pp:NaN12327-12327
Publication Date(Web):2015/11/13
DOI:10.1039/C5TC03165F
Red Li3BaSrLa3(WO4)8:Eu3+ phosphors have been successfully synthesized by a rapid microwave-assisted solid state method. The sintering time for the optimal phosphor can be limited to only 10 minutes at 900 °C. Upon near-ultra-violet (NUV) excitation, strong red emission can be found in 90% Eu3+ doped tungstate compounds. This phosphor exhibits impressive thermal stability, and the purity of red emission Li3BaSrLa3(WO4)8:Eu3+ in high Eu3+ doping concentrations can achieve the coordinate values (x = 0.670, y = 0.330), indicating high red color purity. The corresponding quantum yield (QY) is measured (28.36 ± 0.09%). Photoluminescence and kinetic studies showed no obvious effects due to the concentration quenching effect, cross relaxation and non-radiative energy transfer. Li3BaSrLa3(WO4)8:Eu3+ can be synthesized using a simple and quick method and the comprehensive photophysical studies of the novel phosphor (Li3BaSrLa3(WO4)8:Eu3+) have been done and the potential as a practical phosphor for NUV-excited white LEDs (WLEDs) has been shown.
Co-reporter:Chi-Fai Chan, Ming-Kiu Tsang, Hongguang Li, Rongfeng Lan, Frances L. Chadbourne, Wai-Lun Chan, Ga-Lai Law, Steven L. Cobb, Jianhua Hao, Wing-Tak Wong and Ka-Leung Wong
Journal of Materials Chemistry A 2014 - vol. 2(Issue 1) pp:NaN91-91
Publication Date(Web):2013/11/18
DOI:10.1039/C3TB21034K
Inhibition of the CDK4/cyclin D complex through the substrate recruitment site on the cyclin positive regulatory subunit is recognised as being a promising anti-cancer target. Specific peptide sequences can be used to selectively disrupt this target, but the development of peptides as anti-tumor agents in vitro/in vivo presents several obstacles. Poor cell internalization, low sensitivity towards enzymatic degradation in vivo, and ineffectiveness in monitoring via indirect screening are all issues which must be overcome. Herein, we describe the surface functionalization of lanthanide nanoparticles with cyclin D-specific peptides to prepare novel nanomaterials (UCNPs–P1) which can target the CDK4/cyclin D complex. The nanomaterials prepared (UCNPs–P1) are cell permeable and they display parallel emission spectra in vitro and in an aqueous biological environment. They can also be used in low dose concentrations under harmless NIR excitation and emission via upconversion. Uniquely, in addition to acting as a bioimaging probe, UCNPs–P1 also exhibits promising cytotoxicity towards cancer cells. In light of the aforementioned properties, the prepared functionalized nanomaterials (UCNPs–P1) offer the first real dual acting system for cyclin D imaging and simultaneous inhibition of cancer cell division.
Co-reporter:Chi-Fai Chan, Rongfeng Lan, Ming-Kiu Tsang, Di Zhou, Sam Lear, Wai-Lun Chan, Steven L. Cobb, Wai-Kwok Wong, Jianhua Hao, Wing-Tak Wong and Ka-Leung Wong
Journal of Materials Chemistry A 2015 - vol. 3(Issue 13) pp:NaN2634-2634
Publication Date(Web):2015/02/05
DOI:10.1039/C4TB02104E
Polo-like kinase 1 (Plk1) is a major serine/threonine protein kinase which regulates key mitotic events such as centrosome duplication, spindle assembly and chromosome separation. Overexpression and aberrant activities of Plk1 can be detected in different types of cancer. Given that the unique polo box domain (PBD) pocket provides an excellent drug target for Plk1 binding and inhibition, we have rationally designed multifunctional lanthanide-doped upconversion nanomaterials. NaGdF4:Yb3+, Er3+ (NaGdF4) and BaGdF5:Yb3+, Er3+ (BaGdF5) nanoparticles of two different sizes (60 nm and 10 nm, respectively) have been thin-coated with Plk1 specific peptides (–P1 = PLHSpT, –P2 = PLHSD, and –P3 = GGPLHSpT) to prepare novel nanomaterials. Comparative studies on cellular uptake, anti-cancer activity and imaging properties were then carried out. The experimental data obtained support our original hypothesis that the designed nanomaterials can successfully deliver Plk1 specific peptides into cancer cells causing Plk1 inhibition while simultaneously allowing direct NIR imaging and monitoring. Among the NaGdF4–Pn and BaGdF5–Pn nanoparticle series prepared in this study, NaGdF4–P1 emerged as the best candidate for Plk1 binding and imaging. NaGdF4–P1 can effectively exert cell cycle G2/M arrest and thus selective tumor inhibition both in vitro and in vivo and as such it offers a potentially interesting system for the development of new cancer therapies.
Co-reporter:Hongguang Li, Frances L. Chadbourne, Rongfeng Lan, Chi-Fai Chan, Wai-Lun Chan, Ga-Lai Law, Chi-Sing Lee, Steven L. Cobb and Ka-Leung Wong
Dalton Transactions 2013 - vol. 42(Issue 37) pp:NaN13501-13501
Publication Date(Web):2013/07/08
DOI:10.1039/C3DT51053K
Six water-soluble europium complexes (Eu–L11–Pnnn and Eu–L22–Pnnn, n = 1, 2 and 3) with one antenna chromophore, two different linkers (L11 and L22) and three proposed cyclin A specific peptides (P11: -GAKRRLIF-NH2; P22: -GGAKRRLIF-NH2; P33: -Hex- GAKRRLIF-NH2) have been synthesized. With structural information available, comparisons of the cyclin grooves of cyclin A and the six europium complexes have been made, and insights have been gained into the determinants for peptide binding and the foundation of differential binding. Experiment-wise, the linear and two-photon induced photophysical properties of these conjugates were monitored in aqueous solution. Numerous in situ/in vitro biological assays have been carried out, such as responsive emission changes in situ/in vitro, Western blot and cellular uptake. As imaging agents, complexes with peptides P33: -Hex-GAKRRLIF-NH2 showed high selectivity to cyclin A in numerous cancer cells. When it comes to responsive optical signal changes, complex Eu–L22–P33 exhibited a threefold emission enhancement upon binding with cyclin A (100 nM cyclin A, ϕ = 8% to 21%, log KB = 5.83, detection limit = 5 nM), and this could be initiated by the shortened distance between the antenna and the lanthanide after they bind/get into cyclin A. It is promising that our compounds (especially compound Eu–L22–P33) could serve as the template for structure-guided efforts to develop potential imaging therapeutics on the basis of selective imaging of CDK2/cyclin A activity.
Co-reporter:Sizhe Zhu, Si Yao, Fengshou Wu, Lijun Jiang, Ka-Leung Wong, Ji Zhou and Kai Wang
Organic & Biomolecular Chemistry 2017 - vol. 15(Issue 27) pp:NaN5771-5771
Publication Date(Web):2017/06/20
DOI:10.1039/C7OB01003F
Organelle and nucleus dual-targeted anticancer drugs are being increasingly used for efficient cancer therapy as they can attack the double vital sites of tumor cells. In this work, we synthesized and characterized two new porphyrin compounds Pt-Por-RB and Me-Por-RB. The spectral titration results suggest that both Pt-Por-RB and Me-Por-RB bind to DNA efficiently in an intercalation binding mode. Upon irradiation, Pt-Por-RB with low dark-cytotoxicity can rapidly generate singlet oxygen to damage the tumor cells through the process of photodynamic therapy. Compared with Me-Por-RB, Pt-Por-RB was not only internalized in the organelles, but also in the nuclei of HeLa cells, probably due to the presence of platinum complexes, as analyzed using the confocal laser scanning microscope. Thus, with the combination of organelle and nucleus dual-targeting property and high efficiency of singlet oxygen generation, Pt-Por-RB showed a significant therapeutic activity against tumor cells.
Co-reporter:Hongguang Li, Rongfeng Lan, Chi-Fai Chan, Guochen Bao, Chen Xie, Pak-Ho Chu, William C. S. Tai, Shuai Zha, Jing-Xiang Zhang and Ka-Leung Wong
Chemical Communications 2017 - vol. 53(Issue 52) pp:NaN7087-7087
Publication Date(Web):2017/06/08
DOI:10.1039/C7CC03021E
We report a direct imaging tool, HGEu001, for primary cilia in living cells, which is specific, and based on the UV light or near infrared laser (via two-photon excitation) induced long-lived europium luminescence.
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