Co-reporter:Xuling Xue, Chengcheng Zhu, Huachao Chen, Yang Bai, Xiangchao Shi, Yang Jiao, Zhongyan Chen, Yupeng Miao, Weijiang He, and Zijian Guo
Inorganic Chemistry April 3, 2017 Volume 56(Issue 7) pp:3754-3754
Publication Date(Web):December 6, 2016
DOI:10.1021/acs.inorgchem.6b02148
Sensitizing the antitumor activity of monofunctional PtII complexes is a reliable approach to developing antitumor agents different from the classic Pt-based drugs. Considering the poor intracellular accumulation of monofunctional PtII complexes, in this study, the photosensitizing monofunctional PtII complex Pt-BA was derived from a weak BODIPY (boron-dipyrromethene)-derived photosensitizer BA, with the purpose to improve its antitumor cytotoxicity via enhancing its intracellular accumulation with a short time photo-irradiation. Photoinduced reactive oxygen species (ROS) determination indicated that the PtII center in Pt-BA is able to improve the photoinduced ROS production ability of BA, which makes Pt-BA a mild photosensitizer. Fluorescence imaging disclosed that dark incubation makes Pt-BA accumulate mainly on the surface of cell membrane, and the later short time photo-irradiation (5 min) promotes distinctly the intracellular accumulation of Pt-BA, which has been confirmed by inductively coupled plasma–mass spectrometry determination. Flow cytometric Annexin V-FITC assay indicated that the short time irradiation of Pt-BA induces in situ the cell membrane damage, which might finally enhance the intracellular accumulation of this monofunctional complex. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay confirmed that the short time photo-irradiation promotes distinctly the antitumor cytotoxicity of Pt-BA against MCF-7, SGC-7901, A549, and HeLa cell lines. The photopromoted antitumor activity of Pt-BA implies that modifying monofunctional PtII complex as a mild photosensitizer to promote its cell accumulation is a useful approach to sensitizing the antitumor activity of monofunctional PtII complex and renders the possibility of monofunctional PtII prodrugs for precise chemotherapy via only short time photoactivation.
Co-reporter:Huachao Chen;Jiangwei Tian;Danyang Liu;Weijiang He
Journal of Materials Chemistry B 2017 vol. 5(Issue 5) pp:972-979
Publication Date(Web):2017/02/01
DOI:10.1039/C6TB02714H
A smart dendrigraft poly-L-lysine (DGL) nanoplatform for mitochondria-targeted chemotherapy was devised, which aims to achieve enhanced efficacy against drug resistant tumor cells. In this system, doxorubicin (Dox) was intercalated into the DNA duplex containing an ATP aptamer, which was subsequently condensed by DGL to form a nanoscaled controlled-release system. A nucleolin-specific binding aptamer, AS1411, and a cytochrome c aptamer were then incorporated into the system to give the nanoparticles (Dox/Mito-DGL) for biological evaluations. This dual modified system has been shown to selectively accumulate in the mitochondria of cancer cells and promptly release the loaded Dox in virtue of the high concentrations of ATP in mitochondria. The mitochondria-specific and spatiotemporally controlled release of Dox led to enhanced therapeutic outcomes both in vitro and in vivo. More significantly, Dox/Mito-DGL was successfully applied to improve the efficacy towards multi-drug resistant cancer cells by altering the mitochondrial membrane potential and bypassing the P-glycoprotein-mediated drug efflux. This work presents a paradigm for mitochondria-targeting therapy against mitochondria-associated diseases and provides a potential avenue for overcoming MDR in the treatment of solid tumors.
Co-reporter:Yang Jiao;Jianping Zhu;Yan Guo;Weijiang He
Journal of Materials Chemistry C 2017 vol. 5(Issue 21) pp:5214-5222
Publication Date(Web):2017/06/01
DOI:10.1039/C7TC00507E
A simple spin crossover (SCO) complex, [Fe(bpp)2][BF4]2 (bpp = 2,6-bis(pyrazol-1-yl)pyridine), was found to exhibit luminesce with a broad band from 425 to 565 nm in the solid state at ambient temperature, although it was non-luminescent at <250 K. In addition, an abrupt enhancement in luminescence was found at ∼260 K, which is exactly the temperature for a transition from the low spin (LS) to the high spin (HS) state of the complex. This implied that the luminescence was triggered by the thermal spin transition from the LS to HS state, which was different from the emission quenching effect of a normal paramagnetic metal center. A theoretical study via DFT calculations suggested that the excitation efficiency of the complex from the ground state to the lowest excited state for the HS state was higher than that for the LS state, which was proposed to be the reason for the HS-triggered luminescence. A hole/electron excitation analysis and orbital component analysis demonstrated that metal to ligand charge transfer (MLCT) upon excitation was responsible for the luminescence of this complex. This is the first report about the MLCT luminescence of SCO Fe(II) complex tuned by the thermal spin transition. Although the HS-triggered luminescence of solid [Fe(bpp)2][BF4]2 was very weak and not suitable for practical applications, molecular materials for both the multiple readout application and magnetism-regulated optical signaling could be anticipated by improving the luminescence efficiency of this type of SCO complexes in the future.
Co-reporter:Nafees Muhammad;Nasreen Sadia;Chengcheng Zhu;Cheng Luo;Xiaoyong Wang
Chemical Communications 2017 vol. 53(Issue 72) pp:9971-9974
Publication Date(Web):2017/09/05
DOI:10.1039/C7CC05311H
A biotin-guided platinumIV complex is highly cytotoxic against breast cancer cells but hypotoxic against mammary epithelial cells. The mono-biotinylated PtIV complex is superior to the di-biotinylated one and hence a promising drug candidate for the targeted therapy of breast cancer.
Co-reporter:Zhenzhu Zhu, Zenghui Wang, Yigang Hao, Chengcheng Zhu, Yang Jiao, Huachao Chen, Yun-Ming Wang, Jun Yan, Zijian Guo and Xiaoyong Wang
Chemical Science 2016 vol. 7(Issue 4) pp:2864-2869
Publication Date(Web):20 Jan 2016
DOI:10.1039/C5SC04049C
Superparamagnetic iron oxide nanoparticles (SPIONs) are potential vehicles for targeted drug delivery and viable contrast agents for magnetic resonance imaging (MRI). A PtIV prodrug (HSPt) derived from functionalization of cisplatin with hydroxyl and succinate is conjugated with a poly(ethylene glycol) (PEG)-modified SPION for cancer therapy and monitoring of therapeutic responses. The relaxivity of HSPt–PEG-SPIONs is larger than that of commercial contrast agent Feridex, and a tumor-selective negative contrast is observed in MRI in a magnetic field. HSPt–PEG-SPIONs can be dissociated and reduced into PtII species by glutathione (GSH). Instead of forming DNA–Pt crosslinks, the reduced product induces direct DNA single- or double-strand breaks, which is uncommon for Pt drugs. The cytotoxicity of HSPt–PEG-SPIONs is positively correlated with the GSH level of tumor cells, which is opposite to the scenario of current Pt drugs. HSPt–PEG-SPIONs are as cytotoxic as cisplatin against cancer cells but are almost nontoxic towards normal cells. Since the mechanism of action of the nanocomposite is different from the established paradigm for Pt drugs, it may become a special theranostic agent for cancer treatment.
Co-reporter:Mingmin Wu, Xiaoyong Wang, Kun Wang and Zijian Guo
Chemical Communications 2016 vol. 52(Issue 54) pp:8377-8380
Publication Date(Web):07 Jun 2016
DOI:10.1039/C6CC02674E
A general detection method for DNA methylation is developed based on the FRET mechanism between upconversion nanoparticles and gold nanorods, which can recognize the cytosine methylation in a known DNA strand at a concentration as low as 7 pM.
Co-reporter:Nafees Muhammad, Xiaoyong Wang, Kun Wang, Chengcheng Zhu, Zhenzhu Zhu, Yang Jiao and Zijian Guo
Dalton Transactions 2016 vol. 45(Issue 33) pp:13169-13178
Publication Date(Web):09 Jun 2016
DOI:10.1039/C6DT01434H
Drug resistance and unfavorable pharmacokinetics are the major obstacles for conventional anticancer drugs. A combination of different anticancer drugs into one formulation is a common strategy to alleviate the side effects of individual drugs in clinical practice. Platinum anticancer drugs are the typical defective therapeutic agents for cancer chemotherapy and have poor selectivity for tumor cells. In this study, a nanosystem composed of poly(lactic-co-glycolic acid) (PLGA), PtIV prodrug (PPD) and α-tocopheryl succinate (α-TOS) was designed to overcome these defects. The PtIV prodrug, c,c,t-[Pt(NH3)2Cl2(O2CC(CH3)3)2], was prepared by the reaction of oxoplatin with trimethylacetic anhydride and its structure was characterized by X-ray crystallography. The PPD and α-TOS self-assembled with PLGA, forming a dual-drug loaded nanoparticle (DDNP). The surface of the DDNP was decorated with galactosamine (G), giving rise to a G-DDNP that can actively target the liver cancer cells through the overexpressed asialoglycoprotein receptors. The DDNPs and G-DDNPs were characterized by SEM, TEM, and DLS. They are spherical in shape with required polydispersity and suitable mean size (ca. 150 nm). The in vitro cytotoxicity of DDNPs and G-DDNPs was tested against the human SMMC-7721 liver cancer cell line. G-DDNPs are more potent than the corresponding free drugs and untargeted DDNP, showing that some synergistic and tumor-specific effects are achieved by this strategy. The results demonstrate that dual-drug loaded nanoformulations with tumor-targeting function could be effective anticancer agents for conquering the shortcomings related to single-drug chemotherapy.
Co-reporter:Yuncong Chen, Yang Bai, Zhong Han, Weijiang He and Zijian Guo
Chemical Society Reviews 2015 vol. 44(Issue 14) pp:4517-4546
Publication Date(Web):09 Mar 2015
DOI:10.1039/C5CS00005J
Zn2+ plays essential roles in various physiological processes in living systems, and the investigation of Zn2+ related physiology and pathology has attracted considerable interest. Because photoluminescence (PL) imaging possesses distinct advantages, such as high sensitivity and non-invasiveness, and excellent temporal and spatial resolution, it has become a powerful tool for the real time monitoring of Zn2+ distribution, uptake, and trafficking. Over the last two decades, great efforts have been devoted to PL Zn2+ imaging in living systems, which proved the Zn2+ fluctuations in physiological processes and the temporal-spatial distribution of labile Zn2+ as well as the localization of labile Zn2+ pools. Advances in PL techniques, such as fluorescence microscopy, confocal fluorescence microscopy, two photon fluorescence microscopy, lifetime based techniques and luminescence optical imaging systems, have made remarkable contributions in tackling major challenges in Zn2+ PL imaging. With the rational design and proper use of fluorescent sensors, Zn2+ imaging in various cell lines, organelles, tissues, organs and living animals has been realized, which was shown to be crucial in elucidating the biological and physiological roles of labile Zn2+.
Co-reporter:Xiaoyong Wang, Xiaohui Wang, and Zijian Guo
Accounts of Chemical Research 2015 Volume 48(Issue 9) pp:2622
Publication Date(Web):August 6, 2015
DOI:10.1021/acs.accounts.5b00203
Platinum-based anticancer drugs are the mainstay of chemotherapy regimens in clinic. Nevertheless, the efficacy of platinum drugs is badly affected by serious systemic toxicities and drug resistance, and the pharmacokinetics of most platinum drugs is largely unknown. In recent years, a keen interest in functionalizing platinum complexes with bioactive molecules, targeting groups, photosensitizers, fluorophores, or nanomaterials has been sparked among chemical and biomedical researchers. The motivation for functionalization comes from some of the following demands: to improve the tumor selectivity or minimize the systemic toxicity of the drugs, to enhance the cellular accumulation of the drugs, to overcome the tumor resistance to the drugs, to visualize the drug molecules in vitro or in vivo, to achieve a synergistic anticancer effect between different therapeutic modalities, or to add extra functionality to the drugs.In this Account, we present different strategies being used for functionalizing platinum complexes, including conjugation with bisphosphonates, peptides, receptor-specific ligands, polymers, nanoparticles, magnetic resonance imaging contrast agents, metal chelators, or photosensitizers. Among them, bisphosphonates, peptides, and receptor-specific ligands are used for actively targeted drug delivery, polymers and nanoparticles are for passively targeted drug delivery, magnetic resonance imaging contrast agents are for theranostic purposes, metal chelators are for the treatment or prevention of Alzheimer’s disease (AD), and photosensitizers are for photodynamic therapy of cancers. The rationales behind these designs are explained and justified at the molecular or cellular level, associating with the requirements for diagnosis, therapy, and visualization of biological processes. To illustrate the wide range of opportunities and challenges that are emerging in this realm, representative examples of targeted drug delivery systems, anticancer conjugates, anticancer theranostic agents, and anti-AD compounds relevant to functionalized platinum complexes are provided. All the examples exhibit new potential of platinum complexes for future applications in biomedical areas. The emphases of this Account are placed on the functionalization for targeted drug delivery and theranostic agents. In the end, a general assessment of various strategies has been made according to their major shortcomings and defects. The original information in this Account comes entirely from literature appearing since 2010.
Co-reporter:Huachao Chen; Jiangwei Tian; Weijiang He
Journal of the American Chemical Society 2015 Volume 137(Issue 4) pp:1539-1547
Publication Date(Web):January 9, 2015
DOI:10.1021/ja511420n
The low selectivity of currently available photosensitizers, which causes the treatment-related toxicity and side effects on adjacent normal tissues, is a major limitation for clinical photodynamic therapy (PDT) against cancer. Moreover, since PDT process is strongly oxygen dependent, its therapeutic effect is seriously hindered in hypoxic tumor cells. To overcome these problems, a cell-specific, H2O2-activatable, and O2-evolving PDT nanoparticle (HAOP NP) is developed for highly selective and efficient cancer treatment. The nanoparticle is composed of photosensitizer and catalase in the aqueous core, black hole quencher in the polymeric shell, and functionalized with a tumor targeting ligand c(RGDfK). Once HAOP NP is selectively taken up by αvβ3 integrin-rich tumor cells, the intracellular H2O2 penetrates the shell into the core and is catalyzed by catalase to generate O2, leading to the shell rupture and release of photosensitizer. Under irradiation, the released photosensitizer induces the formation of cytotoxic singlet oxygen (1O2) in the presence of O2 to kill cancer cells. The cell-specific and H2O2-activatable generation of 1O2 selectively destroys cancer cells and prevents the damage to normal cells. More significantly, HAOP NP continuously generates O2 in PDT process, which greatly improves the PDT efficacy in hypoxic tumor. Therefore, this work presents a new paradigm for H2O2-triggered PDT against cancer cells and provides a new avenue for overcoming hypoxia to achieve effective treatment of solid tumors.
Co-reporter:Yuncong Chen, Chengcheng Zhu, Jiajie Cen, Yang Bai, Weijiang He and Zijian Guo
Chemical Science 2015 vol. 6(Issue 5) pp:3187-3194
Publication Date(Web):16 Mar 2015
DOI:10.1039/C4SC04021J
The homeostasis of mitochondrial pH (pHm) is crucial in cell physiology. Developing small-molecular fluorescent sensors for the ratiometric detection of pHm fluctuation is highly demanded yet challenging. A ratiometric pH sensor, Mito-pH, was constructed by integrating a pH-sensitive FITC fluorophore with a pH-insensitive hemicyanine group. The hemicyanine group also acts as the mitochondria targeting group due to its lipophilic cationic nature. Besides its ability to target mitochondria, this sensor provides two ratiometric pH sensing modes, the dual excitation/dual emission mode (Dex/Dem) and dual excitation (Dex) mode, and its linear and reversible ratiometric response range from pH 6.15 to 8.38 makes this sensor suitable for the practical tracking of pHm fluctuation in live cells. With this sensor, stimulated pHm fluctuation has been successfully tracked in a ratiometric manner via both fluorescence imaging and flow cytometry.
Co-reporter:Yafeng He, Yin Ding, Dan Wang, Wanjun Zhang, Weizhong Chen, Xichun Liu, Weijie Qin, Xiaohong Qian, Hao Chen and Zijian Guo
Chemical Science 2015 vol. 6(Issue 3) pp:2074-2078
Publication Date(Web):15 Dec 2014
DOI:10.1039/C4SC03650F
Cisplatin, one of the most effective anticancer drugs, is a DNA-damaging agent that induces cell death primarily by apoptosis. For many years, HMGB1 has been known to be a recognition protein for cisplatin–DNA lesions. Here, an application of a biomolecular probe based on a peptide–oligonucleotide conjugate is presented as a novel method for investigating this recognition process in vivo. Proteins known to be involved in the recognition of cisplatin-damaged DNA were pulled down and identified, including members of the HMGB family and a number of other proteins. Interestingly, at least 4 subforms of HMGB1 bind to cisplatin–DNA adducts. These proteins were further identified as post-translationally acetylated or phosphorylated forms of HMGB1. These results provide a rich pool of protein candidates whose roles in the mechanism of action of platinum drugs should be explored. These newly discovered molecular components of the DNA damage signalling cascade could serve as novel links between the initial cell responses to DNA damage and the downstream apoptotic or DNA repair pathways.
Co-reporter:Yafeng He, Jian Yuan, Yuchen Qiao, Dan Wang, Weizhong Chen, Xichun Liu, Hao Chen and Zijian Guo
Chemical Communications 2015 vol. 51(Issue 74) pp:14064-14067
Publication Date(Web):29 Jul 2015
DOI:10.1039/C5CC05257B
In order to systematically investigate the influence of carrier ligands on the interaction of Pt–DNA adducts with damage recognition proteins, a series of DNA probes containing 1,2-GG platinum compound crosslinks using cisplatin, oxaliplatin, (S,S-DACH)PtCl2 and (cis-1,4-DACH)PtCl2 (kiteplatin) has been constructed. These complexes share similar DNA binding properties although they exhibit quite different cytotoxicity. It is revealed that HMGB1 (high-mobility group protein B1) was the most commonly found protein that recognizes all Pt(II)-DNA probes and prefers cisplatin–DNA probes more than the others. Interestingly, an important component of the replication protein A complex, RPA2, was found to bind to kiteplatin much more tightly than other proteins. These results may be important for the interpretation of the roles of carrier ligands in platinum(II)-based anticancer complexes.
Co-reporter:Fabio Arnesano, Francesco Paolo Fanizzi, Zijian Guo
Journal of Inorganic Biochemistry 2015 Volume 153() pp:204-205
Publication Date(Web):December 2015
DOI:10.1016/j.jinorgbio.2015.11.022
Co-reporter:Wen Zhou, Xiaoyong Wang, Ming Hu, Chengcheng Zhu and Zijian Guo
Chemical Science 2014 vol. 5(Issue 7) pp:2761-2770
Publication Date(Web):11 Mar 2014
DOI:10.1039/C4SC00384E
Copper complexes are potential anticancer drugs by virtue of their available redox properties and low toxicity. In this study, a copper(II) complex, [Cu(ttpy-tpp)Br2]Br (simplified as CTB, ttpy-tpp = 4′-p-tolyl-(2,2′:6′,2′′-terpyridyl)triphenylphosphonium bromide), is synthesized and characterized by X-ray crystallography and ESI-MS as a targeted anticancer agent. Triphenylphosphine (TPP) is introduced into the complex for its mitochondrion-targeting ability and lipophilic character. The uptake of CTB by tumor cells and mitochondria was determined by ICP-MS or fluorescence spectrometry. CTB is able to cross the cytoplasmic and mitochondrial membranes of tumor cells and influence the mitochondrial membrane potential more profoundly than the anticancer drug cisplatin. The cytotoxicity of CTB was tested on MCF-7, HeLa, Skov-3, A549 and cisplatin-resistant A549R tumor cells by MTT assay. CTB is more cytotoxic against these cells than cisplatin; particularly, it is highly effective against cisplatin-resistant tumor cells. The interaction between CTB and DNA has been studied by spectroscopic methods and agarose gel electrophoresis. CTB strongly interacts with DNA via intercalation stabilized by electrostatic forces, and displays a significant cleavage activity towards supercoiled pBR322 DNA and cellular DNA through an oxidative mechanism. The cytotoxicity of CTB seems to result from multiple mechanisms of action, including the modification of DNA conformation, generation of reactive oxygen species, scission of DNA strands, and dissipation of mitochondrial membrane potential. The delocalized cationic property and high hydrophilicity of CTB favours its selective accumulation in cancer cells and mitochondria. This study demonstrates that copper complexes with mitochondrion-targeting function could be efficient anticancer drugs immune to the drug resistance of cisplatin.
Co-reporter:Lin Qiu, Chengcheng Zhu, Huachao Chen, Ming Hu, Weijiang He and Zijian Guo
Chemical Communications 2014 vol. 50(Issue 35) pp:4631-4634
Publication Date(Web):11 Mar 2014
DOI:10.1039/C3CC49482A
Integrating N2-hydroxyethyldiethylenetriamine with anthracene gives a [2+2] macrocycle fluorescent sensor. This sensor displays an instant/reversible turn-on response specific to Fe3+, which allows facile visualization of the Fe3+/Fe2+ transition and intracellular Fe3+ imaging.
Co-reporter:Zhipeng Liu, Changli Zhang, Yuncong Chen, Fang Qian, Yang Bai, Weijiang He and Zijian Guo
Chemical Communications 2014 vol. 50(Issue 10) pp:1253-1255
Publication Date(Web):26 Nov 2013
DOI:10.1039/C3CC46262E
A visible light excitable ratiometric Zn2+ sensor was developed by integrating a Zn2+ chelator as the ICT donor of the fluorophore sulfamoylbenzoxadiazole, which displays the Zn2+-induced hypsochromic emission shift (40 nm) and favors the in vivo ratiometric Zn2+ imaging in zebrafish larvae.
Co-reporter:Huachao Chen, Weijiang He and Zijian Guo
Chemical Communications 2014 vol. 50(Issue 68) pp:9714-9717
Publication Date(Web):25 Jun 2014
DOI:10.1039/C4CC03385J
Synergistic release of platinum anticancer drugs and O2 can be achieved in an H2O2-responsive nanocarrier incorporated with catalase. Such a system combines the advantages of chemotherapy and oxygen therapy and demonstrated improved therapeutic efficacy against cisplatin resistant cell lines which often appear to be in hypoxia.
Co-reporter:Shangnong Wu, Xiaoyong Wang, Yafeng He, Zhenzhu Zhu, Chengcheng Zhu, Zijian Guo
Journal of Inorganic Biochemistry 2014 Volume 139() pp:77-84
Publication Date(Web):October 2014
DOI:10.1016/j.jinorgbio.2014.06.006
Polynuclear platinum complexes constitute a special class of hopeful antitumor agents. In this study, a Y-type monofunctional trinuclear platinum complex (MTPC) with 1,3,5-tris(pyridin-2-ylmethoxy)benzene, ammine and chloride as ligands was synthesized and characterized by 1H NMR and electrospray ionization mass spectrometry (ESI-MS). The DNA binding mode of MTPC was investigated using circular dichroism spectroscopy and gel electrophoresis, and the reactivity of MTPC towards glutathione was studied by 1H NMR and ESI-MS. The results show that MTPC can affect the conformation of calf-thymus DNA (CT-DNA) significantly and tends to form 1,4-GG rather than 1,2-GG intrastrand crosslinks, which are different from the instance of cisplatin. MTPC reacts with glutathione quite slowly in comparison with cisplatin because of the steric hindrance. The cytotoxicity of MTPC was tested on the human breast cancer cell line MCF-7, the human non-small-cell lung cancer cell line A549, and the human ovarian cancer cell line Skov-3 by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. MTPC is more potent than or comparable to cisplatin. The cellular inhibition mode of MTPC was examined by flow cytometry using MCF-7 cells. MTPC arrests the cell cycle mainly in G2 or M phase, while cisplatin arrests the cell cycle in S phase. Similar to cisplatin, MTPC kills the cells predominantly through an apoptotic pathway.Polynuclear platinum complex MTPC reacts with DNA to produce 1,4-GG intrastrand adduct and bring potent cytotoxicity against cancer cells. Unlike cisplatin, MTPC arrests the cell cycle mainly in G2 or M phase.
Co-reporter:Zhenzhu Zhu;Dr. Xiaoyong Wang;Dr. Tuanjie Li;Dr. Silvio Aime;Dr. Peter J. Sadler;Dr. Zijian Guo
Angewandte Chemie International Edition 2014 Volume 53( Issue 48) pp:13225-13228
Publication Date(Web):
DOI:10.1002/anie.201407406
Abstract
Theranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)–gadolinium(III) complexes with the formula [{Pt(NH3)2Cl}2GdL](NO3)2 possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt–Gd complexes is comparable to that of cisplatin at high concentrations (≥0.1 mM), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd–DTPA. T1-weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt–Gd complexes promising theranostic agents for cancer treatment.
Co-reporter:Zhipeng Liu, Weijiang He and Zijian Guo
Chemical Society Reviews 2013 vol. 42(Issue 4) pp:1568-1600
Publication Date(Web):18 Jan 2013
DOI:10.1039/C2CS35363F
Coordination chemistry plays an essential role in the design of photoluminescent probes for metal ions. Metal coordination to organic dyes induces distinct optical responses which signal the presence of metal species of interest. Luminescent lanthanide (Ln3+) and transition metal complexes of d6, d8 and d10 configurations often exhibit unique luminescence properties different from organic dyes, such as high quantum yield, large Stokes shift, long emission wavelength and emission lifetimes, low sensitivity to microenvironments, and can be explored as lumophores to construct probes for metal ions, anions and neutral species. In this review, the design principles and coordination chemistry of metal probes based on mechanisms of PeT, PCT, ESIPT, FRET, and excimer formation will be discussed in detail. Particular attention will be given to rationales for the design of turn-on and ratiometric probes. Moreover, phosphorescent probe design based on Ln3+ and d6, d8 and d10-metal complexes are also presented via discussing certain factors affecting the phosphorescence of these metal complexes. A survey of the latest progress in photoluminescent probes for identification of essential metal cations in the human body or toxic metal cations in the environment will be presented focusing on their design rationales and sensing behaviors. Metal complex-based photoluminescent probes for biorelated anions such as PPi, and neutral biomolecules ATP, NO, and H2S will be discussed also in the context of their metal coordination-related sensing behaviors and design approaches.
Co-reporter:Xiaoyong Wang and Zijian Guo
Chemical Society Reviews 2013 vol. 42(Issue 1) pp:202-224
Publication Date(Web):05 Oct 2012
DOI:10.1039/C2CS35259A
Platinum-based anticancer drugs occupy a crucial role in the treatment of various malignant tumours. However, the efficacy and applicability of platinum drugs are heavily restricted by severe systemic toxicities and drug resistance. Different drug targeting and delivery (DTD) strategies have been developed to prevent the shortcomings of platinum-based chemotherapy. These approaches can be roughly categorized into two groups; namely, active and passive tactics. Active DTD is realized through specific molecular interactions between the drugs and cell or tissue elements, while passive DTD is achieved by exploiting the enhanced permeability and retention effect in tumour tissues. The principal methods for active DTD include conjugation of platinum drugs with selective targeting moieties or encapsulation of platinum drugs in host molecules. Bioactive substances such as hormones, carbohydrates, bisphosphonates, peptides and proteins are commonly used in active DTD. Passive DTD generally involves the fabrication of functionalized polymers or nanoparticles and the subsequent conjugation of platinum drugs with such entities. Polymeric micelles, liposomes, nanotubes and nanoparticles are frequently used in passive DTD. In some cases, both active and passive mechanisms are involved in one DTD system. This review concentrates on various targeting and delivery techniques for improving the efficacy and reducing the side effects of platinum-based anticancer drugs. The content covers most of the related literatures published since 2006. These innovative tactics represent current state-of-the-art developments in platinum-based anticancer drugs.
Co-reporter:Xiaohui Wang, Xiaoyong Wang, Shanshan Cui, Yan Wang, Guangju Chen and Zijian Guo
Chemical Science 2013 vol. 4(Issue 9) pp:3748-3752
Publication Date(Web):16 Jul 2013
DOI:10.1039/C3SC51781K
Recognition of DNA depurination is of great importance for early cancer detection. Current analytical methods for this purpose are usually complicated. Luminescent lanthanide complexes possess some fascinating optical properties that have shown potential applications in biomedical research. In this study, a novel terbium(III) complex (TbL) has been demonstrated to be capable of recognizing purine nucleobases in DNA as a selective time-resolved luminescence probe. TbL consists of a luminescent terbium(III) center and two nitroimidazole groups linked by a linear polydentate ligand. The luminescence of TbL is enhanced remarkably upon reaction with oligonucleotides or natural DNA containing purine bases in aqueous solution, while it is quenched dramatically as depurination occurs to DNA. Mechanistic studies using circular dichroism and fluorescence spectroscopies reveal that the luminescence enhancement results from the preferential intercalation between the nitroimidazole moieties of TbL and the purine bases of DNA, which regulate the electron withdrawing effect of nitro groups via hydrogen bonds and thereby affect the energy transfer from the ligand to the metal center of the probe. This mechanism is also supported by molecular dynamics simulation results for the reaction. The distinct luminescence responses of TbL in the presence and absence of purine bases in DNA make it a sensitive probe for DNA depurination in physiological conditions.
Co-reporter:Jinzhuan Wang, Xiaoyong Wang, Yajie Song, Jing Wang, Changli Zhang, Cunjie Chang, Jun Yan, Lin Qiu, Mingmin Wu and Zijian Guo
Chemical Science 2013 vol. 4(Issue 6) pp:2605-2612
Publication Date(Web):15 Apr 2013
DOI:10.1039/C3SC50554E
Superparamagnetic iron oxide nanoparticles (SPION) are potential drug carriers and a magnetic resonance imaging (MRI) contrast agent for cancer therapy and diagnosis. In this study, dechlorinated cisplatin (CMDP) is tethered to maghemite nanoparticles modified with 4-oxo-4-(3-(triethoxysilyl)propylamino)butanoic acid (OTPBA–SPION) through the surface carboxylate groups. The nanocomposite (CMDP–OTPBA–SPION) was characterized by TEM, XPS, EDX, SQUID, ICP-AES, and zeta potential. A relatively high Pt loading capacity (ca. 13%) is achieved with this drug delivery system. The DNA binding ability of CMDP–OTPBA–SPION is prominent in acidic medium (pH 5.2) but is insignificant under normal physiological conditions (pH 7.4), suggesting that an acidic cancerous environment is favourable for the release of the platinum pharmacophore from the composite. The transverse relaxivity of CMDP–OTPBA–SPION in phosphate-buffered saline is 141.9 mM−1 s−1 in terms of Fe concentration, implying that the composite could be used as a negative-contrast agent for MRI. The cytotoxicity of the composite toward MCF-7 and HeLa cancer cells displays slow and time-dependent characteristics, reaching a level comparable to that of cisplatin at 72 h. The diagnostic capability and tumor-specific accumulation of the composite are verified in vitro and in vivo by the time-dependent negative-contrast enhancement effect in MRI using MCF-7 cells and tumor-bearing mice, respectively. The results demonstrate that CMDP–OTPBA–SPION can potentially be used as an anticancer theranostic agent for simultaneous targeted therapy and MRI under an external magnetic field.
Co-reporter:Changli Zhang, Zhipeng Liu, Yunling Li, Weijiang He, Xiang Gao and Zijian Guo
Chemical Communications 2013 vol. 49(Issue 97) pp:11430-11432
Publication Date(Web):15 Oct 2013
DOI:10.1039/C3CC46862C
A newly developed fluorescent sensor, Naph-BPEA, shows a specific turn-on response to Zn2+ and can be excited by visible light. The in situ nuclear Zn2+ imaging in HeLa and HepG2 cells reveals the nuclear envelope penetrability of the sensor. The specific sensor location in a zebrafish larva was also demonstrated.
Co-reporter:Yuncong Chen, Chengcheng Zhu, Jiajie Cen, Jing Li, Weijiang He, Yang Jiao and Zijian Guo
Chemical Communications 2013 vol. 49(Issue 69) pp:7632-7634
Publication Date(Web):24 Jun 2013
DOI:10.1039/C3CC42959H
ICT fluorophore benzoxadiazole with its electron-donating group modified as a Cu2+ chelator was conjugated with coumarin to construct a new ratiometric sensor with reversible intracellular Cu2+ imaging ability.
Co-reporter:Jinzhuan Wang, Xiaoyong Wang, Yajie Song, Chengcheng Zhu, Jing Wang, Kun Wang and Zijian Guo
Chemical Communications 2013 vol. 49(Issue 27) pp:2786-2788
Publication Date(Web):12 Feb 2013
DOI:10.1039/C3CC39059D
Rhodamine-embedded maghemite nanoparticles could act as fluorescent drug carriers to track and transport platinum anticancer drugs simultaneously.
Co-reporter:Wen Zhou, Xiaoyong Wang, Ming Hu, Zijian Guo
Journal of Inorganic Biochemistry 2013 Volume 121() pp:114-120
Publication Date(Web):April 2013
DOI:10.1016/j.jinorgbio.2012.12.018
Copper complexes are potential metallonucleases that may find application in biotechnology and molecular biology. In this study, a ternary copper–terpyridine complex [Cu(ttpy)(Gly)(NO3)](NO3) · H2O (1) (ttpy = 4′-p-tolyl-2,2′:6,2″-terpyridine) is synthesized and characterized by X-ray crystallography and ESI-MS as an artificial nuclease. Glycine (Gly) is introduced into the complex to enhance the water-solubility and electrostatic affinity for the nucleic acid target. The interaction between complex 1 and DNA has been studied by spectroscopy and gel electrophoresis, using a structural analog [Cu(ttpy)(NO3)2] (2) as the reference. Complex 1 demonstrates an increased DNA binding ability and oxidative cleavage activity towards supercoiled pBR322 DNA as compared with complex 2. The enhanced water-solubility and positive charge of complex 1 may facilitate its access to DNA and formation of hydrogen bonds with the sugar-phosphate backbone. The results indicate that carefully positioned auxiliary groups in a copper complex can significantly affect the substrate binding or activation ability and consequently the nuclease efficiency of the complex.A ternary copper–terpyridine complex with auxiliary glycine ligand demonstrates enhanced DNA binding and cleavage properties due to the increased water-solubility and electrostatic interaction.Highlights► Cu-terpyridine-Gly ternary complex was prepared as an artificial nuclease. ► Gly increased the water-solubility and electrostatic affinity of the complex for DNA. ► Cu-terpyridine-Gly complex showed enhanced abilities in DNA binding and cleavage.
Co-reporter:Yuncong Chen;Chengcheng Zhu;Zhenghao Yang;Junjie Chen;Yafeng He;Yang Jiao; Weijiang He;Lin Qiu;Jiajie Cen ; Zijian Guo
Angewandte Chemie International Edition 2013 Volume 52( Issue 6) pp:1688-1691
Publication Date(Web):
DOI:10.1002/anie.201207701
Co-reporter:Xiaohui Wang, Xiaoyong Wang, Changli Zhang, Yang Jiao and Zijian Guo
Chemical Science 2012 vol. 3(Issue 4) pp:1304-1312
Publication Date(Web):26 Jan 2012
DOI:10.1039/C2SC01100J
Alzheimer's disease (AD) is a neurodegenerative illness associated with amyloid β-peptide (Aβ) aggregation in the brain. Aβ shows high affinity for metal ions such as Zn2+ and Cu2+, which constitutes the major reason for the Aβ aggregation and related neurotoxicity. Metal chelators are potential therapeutic agents for AD because they could sequester metal ions from the Aβ aggregates and reverse the aggregation. In this study, two macrocyclic platiniferous chelators (PC1, PC2) with cyclen as the metal-chelating unit and Pt(bipyridine)Cl2 as the Aβ-binding unit have been designed as novel bifunctional inhibitors of the metal-induced Aβ aggregation. The interactions between the chelators and Aβ40 aggregates are studied by tandem mass spectrometry and 1H NMR. The platinum centers in PC1 and PC2 are shown to coordinate with histidine residues (His-14 or -13) of Aβ40. The inhibitory effect of the chelators on Aβ40 aggregation induced by Zn2+ and Cu2+ ions is investigated using turbidimetry, a BCA protein assay, and transmission electron microscopy. PC1 and PC2 show significant inhibition against the Aβ aggregation and the action is more effective than that exerted by cyclen. By contrast, the corresponding anticancer drug cisplatin exhibits no inhibition against the Aβ aggregation. PC1 and PC2 can also suppress the Cu-Aβ40 mediated generation of reactive oxygen species and their corresponding neurotoxicity in cortical neuronal cells of mice, and reduce the extent of Aβ aggregation in the brain homogenates of transgenic mice. These chelators may work through simultaneous metal chelation and peptide modification to interfere with the Aβ aggregation. Such an intramolecular synergism distinguishes PC1 and PC2 from other chelators as potential anti-AD agents.
Co-reporter:Zhipeng Liu, Changli Zhang, Yuncong Chen, Weijiang He and Zijian Guo
Chemical Communications 2012 vol. 48(Issue 67) pp:8365-8367
Publication Date(Web):02 Jul 2012
DOI:10.1039/C2CC33648K
A mitochondria-targeted fluorescent sensor (Mito-ST), constructed by integrating a sulfamoylbenzoxadiazole fluorophore with a phosphonium group, displays the specific Zn2+-induced hypsochromic shifts of both excitation (69 nm) and emission (35 nm) maxima. Its ratiometric Zn2+ imaging ability via dual excitation mode has been applied in MCF-7 cells to clarify the different behaviours of mitochondrial Zn2+ release stimulated by H2O2 and SNOC.
Co-reporter:Yuncong Chen, Chengcheng Zhu, Zhenghao Yang, Jing Li, Yang Jiao, Weijiang He, Junjie Chen and Zijian Guo
Chemical Communications 2012 vol. 48(Issue 42) pp:5094-5096
Publication Date(Web):28 Mar 2012
DOI:10.1039/C2CC31217D
A novel sensitive and specific Hg2+ chemodosimeter, derived from 1′,3′-dithiane-substituted 2,1,3-benzoxadiazole, displays “turn-on” fluorescent and colorimetric responses via an Hg2+-triggered aldehyde recovery reaction. Its potential to monitor Hg2+ in living organisms has been demonstrated using zebrafish larvae.
Co-reporter:Liangliang Yan, Xiaoyong Wang, Yanqing Wang, Yangmiao Zhang, Yizhi Li, Zijian Guo
Journal of Inorganic Biochemistry 2012 Volume 106(Issue 1) pp:46-51
Publication Date(Web):January 2012
DOI:10.1016/j.jinorgbio.2011.09.032
Palladium(II) complexes are potential antitumor metallodrugs for their chemical resemblance to platinum(II) complexes. Two palladium(II) complexes (1 and 2) in the formula of [PdLnCl] [L1 = N-(tert-butoxycarbonyl)-l-methionine-N′-8-quinolylamide, L2 = L-alanine-N′-8-quinolylamide] have been synthesized accordingly. The structures of the complexes were fully characterized by X-ray crystallography. The palladium(II) center in 1 is coordinated by two N atoms and an S atom from L1 with one chloride anion as the leaving group; while that in 2 is coordinated by three N atoms from L2 with one chloride anion as the leaving group. The interaction between complex 1 and human serum albumin (HSA) has been investigated using fluorescence and circular dichroism spectroscopies. The complex seems to react with HSA chiefly through hydrophobic and electrostatic interactions, and it does not alter the α-helical nature of HSA. The cytotoxicity of these complexes has been tested against the human cervical cancer (HeLa), human mammary cancer (MCF-7), and human lung cancer (A-549) cell lines. Complex 1 displays a cytotoxic activity comparable to that of cisplatin, but complex 2 is less active than cisplatin.Palladium(II) complexes of ligands with steric hindrance could be equally cytotoxic toward tumor cells but less active to human serum albumin in comparison with cisplatin.Highlights► Pd(II) complexes of quinoline derivatives with monofunctional structural features ► Pd(II) complexes binds to serum albumin through non-covalent interactions ► Pd(II) complexes demonstrate comparable cytotoxicity to cisplatin
Co-reporter:Di Liu, Jialiu Ma, Wen Zhou, Weijiang He, Zijian Guo
Inorganica Chimica Acta 2012 Volume 393() pp:198-203
Publication Date(Web):1 December 2012
DOI:10.1016/j.ica.2012.06.047
Co-reporter:Ruimin Xing, Xiaoyong Wang, Changli Zhang, Jinzhuan Wang, Yangmiao Zhang, You Song and Zijian Guo
Journal of Materials Chemistry A 2011 vol. 21(Issue 30) pp:11142-11149
Publication Date(Web):27 Jun 2011
DOI:10.1039/C1JM11369K
Magnetic nanoparticles are promising carriers for targeted drug delivery. Superparamagnetic magnetite nanocrystal clusters modified with sodium carboxymethylcellulose were prepared by an in situ hydrothermal procedure in this study. The composition, morphology, and magnetic property of the clusters have been characterized by SEM, TEM, XRD, XPS, TGA, IR, and SQUID. The clusters display excellent dimensional uniformity, strong magnetisability, good aqueous dispersibility, and modifiable functionality. By virtue of the abundant carboxylate groups on the surface of the clusters, dechlorinated cisplatin was tethered to the superparamagnetic nanoparticles. The formation and the magnetism of the conjugate have been confirmed by zeta potential, EDX, ICP-MS, XPS, and SQUID. The magnetic property is well retained in the drug-loaded clusters. In comparison with cisplatin, the conjugate can more readily enter cancer cells and exert higher cytotoxicity towards the human cervical cancer HeLa cells and the human hepatocarcinoma HepG2 cells. These nanoparticles are likely to be used as targeted carriers to deliver platinum anticancer drugs.
Co-reporter:Xiaohui Wang, Xiaoyong Wang, Yanqing Wang and Zijian Guo
Chemical Communications 2011 vol. 47(Issue 28) pp:8127-8129
Publication Date(Web):20 Jun 2011
DOI:10.1039/C1CC12429C
A terbium(III) complex gives off strong luminescence upon reacting with human serum albumin in aqueous solution, which can be used to detect the presence and structural modifications of this protein.
Co-reporter:Yanqing Wang, Xiaoyong Wang, Jing Wang, Yongmei Zhao, Weijiang He, and Zijian Guo
Inorganic Chemistry 2011 Volume 50(Issue 24) pp:12661-12668
Publication Date(Web):November 11, 2011
DOI:10.1021/ic201712e
Interactions between platinum complexes and human serum albumin (HSA) play crucial roles in the metabolism, distribution, and efficacy of platinum-based anticancer drugs. Polynuclear monofunctional platinum(II) complexes represent a new class of anticancer agents that display distinct molecular characters of pharmacological action from those of cisplatin. In this study, the interaction between a trinuclear monofunctional platinum(II) complex, [Pt3LCl3](ClO4)3 (L = N,N,N′,N′,N″,N″-hexakis(2-pyridylmethyl)-1,3,5-tris(aminomethyl)benzene) (1), and HSA was investigated using ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy, circular dichroism spectroscopy, fluorescence spectroscopy, molecular docking, and inductively coupled plasma mass spectrometry. The spectroscopic and thermodynamic data show that the interaction is a spontaneous process with the estimated enthalpy and entropy changes being 14.6 kJ mol–1 and 145.5 J mol–1 K–1, respectively. The reactive sites of HSA to complex 1 mainly locate within its hydrophobic cavity in domain II. Noncovalent actions such as π–π stacking and hydrophobic bonding are the primary contributors to the interaction between HSA and complex 1, which is different from the scenario for cisplatin in similar conditions. The results suggest that the connection between complex 1 and HSA is reversible, and therefore the cytotoxic activity of the complex could be preserved during blood circulation.
Co-reporter:Shengde Wu ; Chengcheng Zhu ; Changli Zhang ; Zhen Yu ; Weijiang He ; Yafeng He ; Yizhi Li ; Jing Wang
Inorganic Chemistry 2011 Volume 50(Issue 23) pp:11847-11849
Publication Date(Web):October 28, 2011
DOI:10.1021/ic201506y
The biological fluorescent distribution of a model antitumor monofunctional platinum(II) complex bearing a 7-nitro-2,1,3-benzoxadiazole fluorophore can be visualized in breast carcinoma MCF-7 cells, pulmonary carcinoma A549 cells, kidney epithelial 293T cells, and zebrafish larva.
Co-reporter:Shengde Wu, Xiaoyong Wang, Chengcheng Zhu, Yajie Song, Jing Wang, Yizhi Li and Zijian Guo
Dalton Transactions 2011 vol. 40(Issue 40) pp:10376-10382
Publication Date(Web):17 Jun 2011
DOI:10.1039/C1DT10555H
Two monofunctional platinum(II) complexes, cis-[PtL(NH3)2Cl]NO3 (1) and cis-[PtL′(NH3)2Cl]NO3 (2) {L = N-methyl-7-nitro-N-(2-(pyridin-2-yl)ethyl)benzo[c][1,2,5]-oxadiazol-4-amine, L′ = 7-nitro-N-(2-(pyridin-2-yl)ethyl)benzo[c][1,2,5] oxadiazol-4-amine}, have been synthesized and characterized. The X-ray single crystal structure of complex 1 shows that platinum(II) is coordinated in a square-planar geometry with a [PtN3Cl] setting. Fluorescence profiles of the complexes show that complex 1 is more suitable for cellular imaging than complex 2. The cellular uptake and distribution of complex 1 in the human cervical cancer HeLa cells were studied using confocal microscopy. Complex 1 enters the cells slowly, induces cytoplasmic vacuolations, and accumulates in the nucleoli. These results suggest that monofunctional platinum(II) complexes can stimulate tumour cells to undergo a nonapoptotic death process, which is distinct from the apoptosis induced by cisplatin.
Co-reporter:Changli Zhang, Yuming Zhang, Yuncong Chen, Zhijun Xie, Zhipeng Liu, Xindian Dong, Weijiang He, Chen Shen, Zijian Guo
Inorganic Chemistry Communications 2011 Volume 14(Issue 1) pp:304-307
Publication Date(Web):January 2011
DOI:10.1016/j.inoche.2010.11.021
The integration of bis(pyridin-2-ylmethyl)amine (BPA) with 8-sulfonamidoquinoline (SQ) resulted in a new fluorescent Zn2+ sensor of 1:1 binding stoichiometry. The synergic Zn2+ coordination of BPA and SQ motifs provides the sensor the advantage over TSQ and its analogues in discriminating mobile Zn2+ from the bound Zn2+ of unoccupied coordination sites in living systems. Its pH-independent Zn2+-enhanced emission in physiological condition and cell permeability make it an effective intracellular Zn2+ imaging agent. This sensor profits also from its confirmed Golgi-preferential affinity, and its pH-independent Zn2+ response in physiological pH range provides it the advantages over other xanthenone-based sensors.The BPA incorporation in 8-sulfonamidoquinoline provides a novel Zn2+ fluorescent sensor BPSQ with 1:1 Zn2+ binding stoichiometry. It possesses the pH-independent sensing behavior, cell permeability and the higher ability than TSQ in discriminating the mobile Zn2+ from those of unoccupied coordination sites in biological systems.Research Highlights► A new sulfonamidoquinoline-based Zn2+ fluorescent sensor. ► The 1:1 Zn2+ binding stoichiometry other than 2:1 of normal TSQ analogues. ► The intracellular Zn2+ imaging ability and Golgi preference. ► Reducing the interference of the partially coordinated Zn2+ with the mobile Zn2+.
Co-reporter:Miaoxin Lin;Xiaoyong Wang;Jianhui Zhu;Damin Fan;Yangmiao Zhang
Apoptosis 2011 Volume 16( Issue 3) pp:288-300
Publication Date(Web):2011 March
DOI:10.1007/s10495-010-0562-0
Polynuclear platinum(II) complexes represent a class of potential anticancer agents that have shown promising pharmacological properties in preclinical studies. The nature of cellular responses induced by these complexes, however, is poorly understood. In this research, the cellular responses of human ovarian cancer COC1 cells to dinuclear platinum(II) complexes {[cis-Pt(NH3)2Cl]2L1}(NO3)2 (1) and {[cis-Pt(NH3)2Cl]2L2}(NO3)2 (2) (L1 = α,α′-diamino-p-xylene, L2 = 4,4′-methylenedianiline) has been studied using cisplatin as a reference. The effect of platinum complexes on the proliferation, death mode, mitochondrial membrane potential, and cell cycle progression has been examined by MTT assay and flow cytometry. The activation of cell cycle checkpoint kinases (CHK1/2), extracellular signal-regulated kinases (ERK1/2), and p38 mitogen-activated protein kinase (p38 MAPK) of the cells by the complexes has also been analyzed using phospho-specific flow cytometry. Complex 1 is more cytotoxic than complex 2 and cisplatin at most concentrations; complex 2 and cisplatin are comparably cytotoxic. These complexes kill the cells through an apoptotic or apoptosis-like pathway characterized by exposure of phosphatidylserine and dissipation of mitochondrial membrane potential. Complex 1 shows the strongest inductive effect on the morphological changes of the cells, followed by cisplatin and complex 2. Complexes 1 and 2 arrest the cell cycle in G2 or M phase, while cisplatin arrests the cell cycle in S phase. The influence of these complexes on CHK1/2, ERK1/2, and p38 MAPK varies with the dose of the drugs or reaction time. Activation of phospho-ERK1/2 and phospho-p38 MAPK by these complexes is closely related to the cytostatic activity. The results demonstrate that dinuclear platinum(II) complexes can induce some cellular responses different from those caused by cisplatin.
Co-reporter:Zuqin Xue, Miaoxin Lin, Jianhui Zhu, Junfeng Zhang, Yizhi Li and Zijian Guo
Chemical Communications 2010 vol. 46(Issue 8) pp:1212-1214
Publication Date(Web):16 Jan 2010
DOI:10.1039/B922222G
Platinum(II) complexes bearing geminal bisphosphonate moieties have excellent solubility in both organic and aqueous solutions and show considerable cytotoxicity against human osteosarcoma (MG-63) and ovarian cancer (COC1) cell lines with different apoptotic pathways from that of cisplatin.
Co-reporter:Zhipeng Liu, Changli Zhang, Weijiang He, Zhenghao Yang, Xiang Gao and Zijian Guo
Chemical Communications 2010 vol. 46(Issue 33) pp:6138-6140
Publication Date(Web):28 Jul 2010
DOI:10.1039/C0CC00662A
A ratiometric fluorescent Cd2+ sensor DBITA which featured the Cd2+-induced red-shift of emission (53 nm) and picomolar sensitivity in both aqueous media and living cells was developed.
Co-reporter:Xindian Dong ; Xiaoyong Wang ; Miaoxin Lin ; Hui Sun ; Xiaoliang Yang
Inorganic Chemistry 2010 Volume 49(Issue 5) pp:2541-2549
Publication Date(Web):February 1, 2010
DOI:10.1021/ic100001x
Copper-based artificial metallonucleases are likely to satisfy more biomedical requirements if their DNA cleavage efficiency and selectivity could be further improved. In this study, two copper(II) complexes, [CuL1Cl2] (1) and [CuL2Cl2] (2), and two copper(II)−platinum(II) heteronuclear complexes, [CuPtL1(DMSO)Cl4] (3) and [CuPtL2(DMSO)Cl4] (4), were synthesized using two bifunctional ligands, N-[4-(2-pyridylmethoxy)benzyl]-N,N-bis(2-pyridylmethyl)amine (L1) and N-[3-(2-pyridylmethoxy)benzyl]-N,N-bis(2-pyridylmethyl)amine (L2). These complexes have been characterized by elemental analysis, electrospray ionization mass spectrometry, IR spectroscopy, and UV−vis spectroscopy. The DNA binding ability of these complexes follows an order of 1 < 2 < 3 < 4, as revealed by the results of spectroscopy and agarose gel electrophoresis studies. Their cleavage activity toward supercoiled pUC19 plasmid DNA is prominent at micromolar concentration levels in the presence of ascorbic acid. The introduction of a platinum(II) center to the copper(II) complexes induces a significant enhancement in cleavage activity as compared with copper(II) complexes alone. These results show that the presence of a platinum(II) center in copper(II) complexes strengthens both their DNA binding ability and DNA cleavage efficiency.
Co-reporter:Qin Liu, Xiaoyong Wang, Xiaoliang Yang, Xiao Liang, Zijian Guo
Journal of Inorganic Biochemistry 2010 Volume 104(Issue 11) pp:1178-1184
Publication Date(Web):November 2010
DOI:10.1016/j.jinorgbio.2010.07.007
Platinum-based anticancer drugs such as cisplatin induce increased oxidative stress and oxidative damage of DNA and other cellular components, while selenium plays an important role in the antioxidant defense system. In this study, the interaction between a platinum(II) methionine (Met) complex [Pt(Met)Cl2] and a diselenide compound selenocystine [(Sec)2] was studied by electrospray ionization mass spectrometry, high performance liquid chromatography mass spectrometry, and 1H NMR spectroscopy. The results demonstrate that the diselenide bond in (Sec)2 can readily and quickly be cleaved by the platinum complex. Formation of the selenocysteine (Sec) bridged dinuclear complex [Pt2(Met-S,N)2(μ-Sec-Se,Cl)]3+ and Sec chelated species [Pt(Met-S,N)(Sec-Se,N)]2+ was identified at neutral and acidic media, which seems to result from the intermediate [Pt(Met-S,N)(Sec-Se)Cl]+. An accelerated formation of S–Se and S–S bonds was also observed when (Sec)2 reacted with excessive glutathione in the presence of [Pt(Met)Cl2]. These results imply that the mechanism of activity and toxicity of platinum drugs may be related to their fast reaction with seleno-containing biomolecules, and the chemoprotective property of selenium agents against cisplatin-induced toxicity could also be connected with such reactions.Diselenide can be readily cleaved by platinum complex, which may relate to the therapeutic and protective mechanism of platinum drugs.
Co-reporter:Zhipeng Liu, Changli Zhang, Weijiang He, Fang Qian, Xiaoliang Yang, Xiang Gao and Zijian Guo
New Journal of Chemistry 2010 vol. 34(Issue 4) pp:656-660
Publication Date(Web):04 Feb 2010
DOI:10.1039/B9NJ00703B
A new charge transfer pH fluorescent probe BTP has been prepared by the ethylene bridging of benzothiazole and pyridine. The probe exhibits a specific fluorescent response to pH with a large Stokes shift, and the pH-induced emission enhancement factor (EEF) is about 22-fold when the pH is increased from 3.2 to 5.2. The presence of metal cations such as Na+, K+, Ca2+, Mg2+ and other transition metal cations does not interfere with its fluorescent pH response. In addition, the intracellular pH fluorescent imaging ability of the probe has been confirmed on macrophage cells using a confocal microscope.
Co-reporter:Xindian Dong;Dr. Xiaoyong Wang;Yafeng He;Zhen Yu;Miaoxin Lin;Changli Zhang;Jing Wang;Yajie Song;Yangmiao Zhang;Zhipeng Liu;Dr. Yizhi Li;Dr. Zijian Guo
Chemistry - A European Journal 2010 Volume 16( Issue 47) pp:14181-14189
Publication Date(Web):
DOI:10.1002/chem.201001457
Abstract
DNA condensing agents play a critical role in gene therapy. A tetranuclear nickel(II) complex, [NiII4(L−2H)(H2O)6(CH3CH2OH)2]⋅6NO3 (L=3,3',5,5'-tetrakis{[(2-hydroxyethyl)(pyridin-2-ylmethyl)amino]methyl}biphenyl-4,4'-diol), has been synthesized as a nonviral vector to induce DNA condensation. X-ray crystallographic data indicate that the complex crystallizes in the monoclinic system with space group P21/n, a=10.291(9), b=24.15(2), c=13.896(11) Å, and β=98.175(13)°. The DNA condensation induced by the complex has been investigated by means of UV/Vis spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy, dynamic light scattering, atomic force microscopy, gel electrophoresis assay, and zeta potential analysis. The complex interacts strongly with DNA through electrostatic attraction and induces its condensation into globular nanoparticles at low concentration. The release of DNA from its compact state has been achieved using the chelator ethylenediaminetetraacetic acid (EDTA) for the first time. Other essential properties, such as DNA cleavage inactivity and biocompatibility, have also been examined in vitro. In general, the complex satisfies the requirements of a gene vector in all of these respects.
Co-reporter:Jiafei Mao, Yangmiao Zhang, Jianhui Zhu, Changli Zhang and Zijian Guo
Chemical Communications 2009 (Issue 8) pp:908-910
Publication Date(Web):19 Jan 2009
DOI:10.1039/B817968A
The combination of a red light PDT agent and a Pt(II)-based chemotherapeutic drug at the molecular level maintains the intrinsic functions of each unit; the conjugated complexes exhibit remarkable photocytoxicity and demonstrate potential to serve as agents for DNA-targeting PDT as well as red light photochemotherapy.
Co-reporter:Tingting Chen, Xiaoyong Wang, Yafeng He, Changli Zhang, Ziyi Wu, Kuo Liao, Jianjun Wang and Zijian Guo
Inorganic Chemistry 2009 Volume 48(Issue 13) pp:5801-5809
Publication Date(Web):June 4, 2009
DOI:10.1021/ic900025x
The aggregation of amyloid β-peptide (Aβ) in plaques in brain tissue is highly associated with Alzheimer’s disease (AD). Aberrant homeostasis of cerebral metals such as Zn2+ and Cu2+ may facilitate the formation of the pathogenetic amyloid plaques. Further, the accumulation of redox-active Cu2+ in these plaques leads to the generation of reactive oxygen species, which mediates the conspicuous oxidative damage to the brain in AD. In this study, the effect of macrocyclic polyamine chelators, cyclen and cyclam, on the aggregation of Aβ40 induced by Zn2+ or Cu2+ was investigated using turbidometry, thioflavin T fluorescence spectroscopy, electrospray ionization mass spectrometry, inductively coupled plasma mass spectrometry, BCA protein assay, circular dichroism spectroscopy, and atomic force microscopy. The solubility of Zn2+- or Cu2+-induced Aβ40 aggregates is greatly increased by cyclen or cyclam as compared to that without chelators, and the solubilization is not affected by other essential metal ions such as Ca2+ and Mg2+. Moreover, the metal-induced β-sheet structure of Aβ40 can be reconverted to its original random coil conformation, and the generation of H2O2 mediated by the Cu-Aβ40 complex can also be inhibited by these chelators. Preliminary tests on neuronal cells indicate that these chelators are capable of reducing the toxicity of metal-Aβ40 aggregates. These observations suggest that cyclen and cyclam could be lead compounds as neuroprotective or neurorescue agents for the treatment of AD.
Co-reporter:Zhaorui Pan, Jiao Xu, Hegen Zheng, Kexuan Huang, Yizhi Li, Zijian Guo and Stuart R. Batten
Inorganic Chemistry 2009 Volume 48(Issue 13) pp:5772-5778
Publication Date(Web):June 5, 2009
DOI:10.1021/ic802457j
Three new heterothiometallic cluster polymers with fascinating topologies have been synthesized by the self-assembly of preformed heterothiometallic cluster monomers and appropriate ligands. Reaction of the monomeric cubic-shaped cluster [Et4N]3[MoOS3Cu3I4] with the D2h symmetry rigid bidentate 4,4′-bipy (4,4′-bipyridine) gave a two-dimensional (2D) layer compound [Mo2O2S6Cu6I2(4,4′-bipy)3(H2O)]n (1); the assembly of pentanuclear cluster monomer [Et4N]4[WS4Cu4I6] with Cs-symmetrical bpe (1,2-bis(4-pyridyl)ethane) afforded a 2D layer compound [WS4Cu4I2(bpe)3(H2O)]n (2), and the assembly of heptanuclear cluster monomer [Et4N]4[WS4Cu6I8] with D3h symmetry trigonal planar ligand timtz (2, 4, 6-tri(1H-imidazol-1-yl)-1, 3, 5-triazine) afforded a three-dimensional (3D) compound [WS4Cu6I4(timtz)8/3(H2O)12]n (3). X-ray crystallographic analysis reveals that 1 crystallizes in trigonal space group R3̅c with 2D 36-hxl net which is the first heterothiometallic superamolecular structure based on a twin cubic-shaped cluster monomer and also the first example of 4,4′-bipy-connected compound of this net. 2 crystallizes in tetragonal space group P42 with distorted 2D 36-hxl net which is the first flexible-ligand-based compound of this topology; while 3 has a 3D net with the high symmetry of cubic space group I4̅3d, and has a novel α-C3N4 topology, which is the maximum symmetry for this net topology. The gas sorption isotherm was measured for 3 to exhibit type-III sorption behavior.
Co-reporter:Jianhui Zhu, Miaoxin Lin, Damin Fan, Ziyi Wu, Yuncong Chen, Junfeng Zhang, Yi Lu and Zijian Guo
Dalton Transactions 2009 (Issue 48) pp:10889-10895
Publication Date(Web):13 Nov 2009
DOI:10.1039/B913236H
The DNA binding ability and binding mode of platinum complexes are crucial factors that govern their cytotoxic activity. In this work, circular dichroism spectroscopy, gel electrophoresis and MALDI-TOF MS spectrometry combined with enzymatic degradation have been used to elucidate the role of bridging ligands in DNA-binding ability and cross-linking patterns of two dinuclear antitumour active platinum(II) complexes, {[cis-Pt(NH3)2Cl]2L1}(NO3)2 (1, L1= 4,4′-methylenedianiline) and {[cis-Pt(NH3)2Cl]2L2}(NO3)2 (2, L2 = α,α′-diamino-p-xylene). Although both complexes have two cis-diammine-Pt(II) moieties (1,1/c,c), complex 1 exhibits much higher DNA-binding ability than complex 2. The former readily forms both 1,3- and 1,4-intrastrand cross-links with DNA oligonucleotides, while the latter preferentially forms 1,4- rather than 1,3-intrastrand cross-links. Cytotoxicity studies against a human non-small-cell lung cancer cell line (A549) demonstrate that complex 1 has higher activity than 2. These results show that the linker properties play a critical role in controlling the DNA-binding and cross-linking abilities and in modulating the cytotoxicity of dinuclear platinum complexes.
Co-reporter:Ruimin Xing, Xiaoyong Wang, Liangliang Yan, Changli Zhang, Zhen Yang, Xinghao Wang and Zijian Guo
Dalton Transactions 2009 (Issue 10) pp:1710-1713
Publication Date(Web):23 Jan 2009
DOI:10.1039/B900256C
Apoferritin-coated photoluminescent CdSe nanoparticles generated by an EDTA-mediated in situ method are photostable, water soluble and biocompatible.
Co-reporter:Guangyu Su, Zhipeng Liu, Zhijun Xie, Fang Qian, Weijiang He and Zijian Guo
Dalton Transactions 2009 (Issue 38) pp:7888-7890
Publication Date(Web):24 Aug 2009
DOI:10.1039/B914802G
Triphosphate or pyrophosphate can be recognised by a diZn2+ complex of bis(BPEA)-appended intramolecular charge transfer fluorophore 4-amino-7-aminosulfonyl-2,1,3-benzoxadiazole, displaying a 5–6 fold fluorescent enhancement at 576 nm.
Co-reporter:Ruimin Xing, Xiaoyong Wang, Changli Zhang, Yangmiao Zhang, Qi Wang, Zhen Yang, Zijian Guo
Journal of Inorganic Biochemistry 2009 Volume 103(Issue 7) pp:1039-1044
Publication Date(Web):July 2009
DOI:10.1016/j.jinorgbio.2009.05.001
Clinical application of platinum-based anticancer drugs is largely limited by severe general toxicity and drug resistance. Drug delivery systems with tumor-targeting potential are highly desired for improving the efficacy and applicability of these drugs. This study describes an alternative strategy for the delivery of platinum drugs (cisplatin, carboplatin and oxaliplatin) by encapsulating each of them in the cavity of apoferritin (AFt). The encapsulation was achieved through manipulating the pH-dependent unfolding–refolding process of AFt at pH 2.0 and 7.4, respectively, in saturated drug solution. UV–vis spectrometry, circular dichroism spectrometry, dynamic light scattering, and inductively coupled plasma mass spectrometry were used to characterize the AFt–drug complexes. The loading capacity of AFt varies with respective drugs and the structural integrity of the protein shell remains intact after encapsulation. In vitro assays on the rat pheochromocytoma cell line (PC12) show that AFt–cisplatin inhibits the cells in a slow but sustaining mode and the cellular uptake of platinum is enhanced by AFt. AFt–carboplatin and AFt–oxaliplatin complexes only exhibit a marginal cytotoxicity towards this cell line under similar concentrations.
Co-reporter:Tuanjie Li, Hao Lin, Tao Li, Weijiang He, Yizhi Li, Yu Zhang, Yangguang Zhu, Zijian Guo
Inorganica Chimica Acta 2009 Volume 362(Issue 3) pp:967-974
Publication Date(Web):20 February 2009
DOI:10.1016/j.ica.2008.01.003
Two binuclear 3N-chelated monofunctional PtII complexes, [Pt2L1Cl2]Cl2 (complex III) and [Pt2L2Cl2]Cl2 (complex IV) [L1 = 3,6,9,16,19,22-hexaazatricyclo[22.2.2.211,14]-triaconta-11,13,24,26(1),27,29-hexaene, L2 = 3,6,9,17,20,23-hexaazatricyclo[23.3.1.111,15]-triaconta-1(29),11(30),12,14,25,27-hexaene] have been synthesized and structurally characterized. Structural determination revealed that each PtII center was coordinated by one chloride anion and three N atoms from each diethylenediamine motif. The Pt–Cl bonds in complex III are shorter than those found in complex IV. The rigid para- and meta-xylylene groups make the two complexes adopt a rigid boat-like conformation and a flexible twisted chair-like conformation, respectively. Moreover, complex III has higher tendency to bind with each other than complex IV. DNA binding studies demonstrated that complex IV could bind effectively with calf thymus DNA, possibly via platination of N7 of guanine residue, while no obvious DNA binding was observed for complex III. However, complex III displays a comparable cytotoxicity to cisplatin against HeLa cell line, while compound IV does not show any effective cell inhibition at low concentration. Therefore, the rigid spacers in complexes III and IV play a determining role in their anti-cancer activity and DNA binding ability.Binuclear PtII complexes formed by para- and meta-xylylene spaced cyclic bisdiens display different cytotoxicity and DNA binding behavior. The rigid spacers in the complexes play a determining role in their anti-cancer activity and DNA binding ability.
Co-reporter:Zihua Xu, Yangmiao Zhang, Zuqin Xue, Xiaoliang Yang, Ziyi Wu, Zijian Guo
Inorganica Chimica Acta 2009 Volume 362(Issue 7) pp:2347-2352
Publication Date(Web):15 May 2009
DOI:10.1016/j.ica.2008.10.021
Co-reporter:Zhengyi Wu;Qin Liu;Xiao Liang
JBIC Journal of Biological Inorganic Chemistry 2009 Volume 14( Issue 8) pp:
Publication Date(Web):2009 November
DOI:10.1007/s00775-009-0576-7
Cellular uptake of platinum-based antitumor drugs is a critical step in the mechanism of the drug action and associated resistance, and deeper understanding of this step may inspire development of novel methods for new drugs with reduced resistance. Human copper transporter 1 (hCtr1), a copper influx protein, was recently found to facilitate the cellular entry of several platinum drugs. In the work reported here, we constructed a Met- and His-rich 20mer peptide (hCtr1-N20) corresponding to the N-terminal domain of hCtr1, which is the essential domain of hCtr1 for transporting platinum drugs. The interactions of the peptide with cisplatin and its analogues, including transplatin, carboplatin, oxaliplatin, and [Pt(l-Met)Cl2], were explored at the molecular level. Electrospray ionization (ESI) mass spectrometry (MS) data revealed that all of the platinum(II) complexes used in present study can bind to hCtr1-N20 in 1:1 and 2:1 stoichiometry. Four Met residues should be involved in binding to cis-platinum complexes on the basis of the tandem MS spectrometry and previously reported data. Time-dependent 2D [1H,15N] heteronuclear single quantum coherence NMR spectra indicate the reaction of cisplatin with hCtr1-N20 is a stepwise process. The intermediate, however, is transient, which is consistent with the ESI-MS results. Time-dependent ESI-MS data revealed that the geometry and the properties of both the leaving and the nonleaving groups of platinum(II) complexes play essential roles in controlling the reactivity and formation of the final products with hCtr1-N20.
Co-reporter:Qin Jiang;Jianhui Zhu;Yangmiao Zhang;Nan Xiao
BioMetals 2009 Volume 22( Issue 2) pp:297-305
Publication Date(Web):2009 April
DOI:10.1007/s10534-008-9166-3
Two zinc(II) terpyridine complexes Zn(atpy)2(PF6)2 (1) (atpy = 4′-p-N9′-adeninylmethylphenyl-2,2′:6,2′′-terpyridine) and Zn(ttpy)2(PF6)2 (2) (ttpy = 4′-p-tolyl-2,2′:6,2′′-terpyridine) have been synthesized and characterized by elemental analysis, 1H NMR and electrospray mass spectroscopy. The structure of complex 2 was also determined by X-ray crystallography, which revealed a ZnN6 coordination in an octahedral geometry with two terpyridine acting as equatorial ligands. The circular dichroism data showed that complex 1 exhibited an ICD signal at around 300 nm and induced more evident disturbances on DNA base stacking than complex 2, reflecting the impact of the adenine moiety on DNA binding modes. Complex 1 exhibited higher cleavage activity to supercoiled pUC 19 DNA than complex 2 under aerobic conditions, suggesting a promotional effect of adenine moiety in DNA nuclease ability. Interestingly, both complexes demonstrated potent in vitro cytotoxicity against a series human tumor cell lines such as human cervix carcinoma cell line (HeLa), human liver carcinoma cell line (HepG2), human galactophore carcinoma cell line (MCF-7) and human prostate carcinoma cell line (pc-3). The cytotoxicity is averagely 10 times more active than the anticancer drug cisplatin.
Co-reporter:Jianhui Zhu;Yongmei Zhao Dr.;Yanyan Zhu;Ziyi Wu;Miaoxin Lin;Weijiang He Dr.;Yan Wang Dr.;Guangju Chen Dr.;Lei Dong Dr.;Junfeng Zhang Dr.;Yi Lu Dr. Dr.
Chemistry - A European Journal 2009 Volume 15( Issue 21) pp:5245-5253
Publication Date(Web):
DOI:10.1002/chem.200900217
Co-reporter:Xiaoyong Wang and Zijian Guo
Dalton Transactions 2008 (Issue 12) pp:1521-1532
Publication Date(Web):04 Dec 2007
DOI:10.1039/B715903J
Metal complexes afford an opportunity for the discovery of new antitumour drugs with truly novel mechanisms of action. Various tactics and some new concepts have been employed to improve the physico-chemical and biological properties of metal complexes. Recent advances in this area demonstrate a bright prospect for the utilization of metal complexes in cancer chemotherapy. The theme of this article focuses on the approaches towards the rational design of platinum(II) and gold(III) complexes with antitumour properties based on the updated understanding of the mechanism of action of these compounds. The complexes summarized in this work include monofunctional platinum(II) complexes, multinuclear platinum(II) complexes, hybrid and targeted platinum(II) complexes, and gold(III) complexes. Most of them violate the established structure-activity relationships and demonstrate different reactivities from cisplatin and thereby show some potential for the prevention of detoxification.
Co-reporter:Qin Jiang, Zhengyi Wu, Yangmiao Zhang, Anna C. G. Hotze, Michael J. Hannon and Zijian Guo
Dalton Transactions 2008 (Issue 23) pp:3054-3060
Publication Date(Web):14 Apr 2008
DOI:10.1039/B719010G
Two novel copper(II) terpyridine complexes, [Cu(atpy)(NO3)(H2O)](NO3)·3H2O (1) and [Cu(ttpy)(NO3)2] (2) (atpy = 4′-p-N9-adeninylmethylphenyl-2,2′:6,2″-terpyridine; ttpy = 4′-p-tolyl-2,2′:6,2″-terpyridine) have been prepared and structurally characterized by X-ray crystallography. Both complexes show a CuN3O2 coordination in a square pyramidal (4 + 1) geometry with terpyridine acting as an equatorial ligand. For complex 1, intermolecular AA base pairing interaction is observed between N6 and N1 of adjacent adenines with N6⋯N1 of 3.027(7) Å. A molecular dynamics simulation of the DNA binding of two complexes showed that the adenine moiety plays an important role in the intercalation of 1 into DNA. This is verified by UV, fluorescence, circular dichroism and flow linear dichroism studies. The promotional effect from the adenine moiety to the intracellular DNA binding of complex 1 is also confirmed by the inductively coupled plasma mass (ICP-MS) spectrometry data which showed a significant higher copper content in DNA isolated from complex 1 treated MCF-7 and HeLa cells.
Co-reporter:Zhanfen Chen, Xiaoyong Wang, Yizhi Li, Zijian Guo
Inorganic Chemistry Communications 2008 Volume 11(Issue 11) pp:1392-1396
Publication Date(Web):November 2008
DOI:10.1016/j.inoche.2008.09.014
Two copper(II) complexes, [CuLCl2] (1) and [Cu3L′Cl6] (2) (L = bis(2-benzimidazolylmethyl)amine, L′ = 2,4,6-tris[bis(2′-benzimidazolylmethyl) amine]-1,3,5-triazine), have been synthesized and characterized. Both complexes bind to DNA and cleave the supercoiled pUC19 plasmid DNA into its nicked and linear forms at micromolar concentrations and physiologically relevant conditions. The DNA cleavage efficacy of 1 is higher than that of 2 though its DNA binding ability is lower than the latter. The cleavage mechanism in the presence of hydrogen peroxide appears to be different for 1 and 2.Mononuclear copper(II) complex of benzimidazole-based ligand shows lower DNA binding ability but higher DNA cleavage activity as compared with its trinuclear analogue.
Co-reporter:Tingting Chen, Xiaoyong Wang, Jiafei Mao, Haiying Wei, Zijian Guo
Inorganic Chemistry Communications 2008 Volume 11(Issue 8) pp:935-938
Publication Date(Web):August 2008
DOI:10.1016/j.inoche.2008.05.007
The electrospray mass spectrometry and NMR spectroscopy techniques reveal that the platinum(II)–methionine complex [Pt(Met)Cl2] binds to the disulfide bond between Cys1 and Cys6 residues of oxytocin (OT). The major adducts identified are [Pt(Met)(OT)]Cl2 species where OT forms five- or six-membered chelates with Pt(II) center. The study suggests that even the oxidized disulfide in oligopeptide still shows a high affinity for platinum complexes, which may be associated with the ubiquity of sulfur-related side effects in platinum anticancer chemotherapy.Platinum(II)–methionine complex [Pt(Met)Cl2] preferentially binds to the disulfide bond between Cys1 and Cys6 residues of oxytocin, forming five- or six-membered chelates [Pt(Met)(OT)]Cl2 as the major products.
Co-reporter:Jun Du, Xiaoyong Wang, Mo Jia, Tuanjie Li, Jiafei Mao, Zijian Guo
Inorganic Chemistry Communications 2008 Volume 11(Issue 9) pp:999-1002
Publication Date(Web):September 2008
DOI:10.1016/j.inoche.2008.05.017
A dizinc complex of 1-[4′-p-tolyl-(2,2′:6′,2″-terpyridyl)]-1,4,7,10-tetraazacyclododecane selectively recognizes phosphate anions in aqueous solution and the recognition process can be sensed by remarkable changes in fluorescence and UV spectroscopy.A dizinc complex of 1-[4′-p-tolyl-(2,2′:6′,2″-terpyridyl)]-1,4,7,10-tetraazacyclododecane demonstrates a selective recognizing ability for phosphate anions, which can be sensed by fluorescence and UV spectroscopy in aqueous solution.
Co-reporter:Qin Jiang, Nan Xiao, Pengfei Shi, Yangguang Zhu, Zijian Guo
Coordination Chemistry Reviews 2007 Volume 251(15–16) pp:1951-1972
Publication Date(Web):August 2007
DOI:10.1016/j.ccr.2007.02.013
The rational design of artificial metallonucleases capable of cleaving DNA in a controllable manner is highly desired due to their potential application in biology and medicine. This review will highlight the most recent progress in the area of artificial metallonucleases employing an oxidative mechanism, focusing on the development of methodologies for cleavage detection, understanding of the factors governing the cleavage efficacy and selectivity, and design strategies for the achievement of high cleavage efficacy. The challenging problems in mimicking the reactivity of natural nucleases will also be discussed.
Co-reporter:Zhen Yang, Xiaoyong Wang, Huajia Diao, Junfeng Zhang, Hongyan Li, Hongzhe Sun and Zijian Guo
Chemical Communications 2007 (Issue 33) pp:3453-3455
Publication Date(Web):17 May 2007
DOI:10.1039/B705326F
Apoferritin derived from the native protein ferritin was employed to encapsulate anticancer drugs cisplatin and carboplatin.
Co-reporter:Zhanfen Chen, Xiaoyong Wang, Yangguang Zhu, Yizhi Li, Zijian Guo
Journal of Inorganic Biochemistry 2007 Volume 101(11–12) pp:1894-1902
Publication Date(Web):November 2007
DOI:10.1016/j.jinorgbio.2007.04.006
A water-soluble dinickel(II) complex of ethylene glycol-bis(β-aminoethyl ether) N,N,N′,N′-tetrakis(2-benzimidazoyl) (EGTB) was synthesized and fully characterized. The complex crystallizes in a monoclinic system with space group P21/c, a = 10.125(1) Å, b = 28.393(3) Å, c = 11.026(1) Å, and β = 98.966(2)°. The hexa-coordinated nickel(II) centers in the centrosymmetric complex adopt a distorted octahedron geometry. The complex binds to purine nucleotides covalently and shows a clear preference for guanosine-5′-monophosphate (5′-GMP) over adenosine-5′-monophosphate (5′-AMP). Its binding to calf thymus DNA (CT-DNA) induces a remarkable conformational variation. The cytotoxic activity of the complex was tested against diverse cell lines including human leukemic cell line U937, macrophage cell line Raw 264.7, human cervical cancer cell line Hela, and human hepatocytes cell line L02. The complex shows a significant inhibition against U937 and Raw 264.7 but little inhibition against Hela and L02.
Co-reporter:Zhanfen Chen, Xiaoyong Wang, Jingwen Chen, Xiaoliang Yang, Yizhi Li and Zijian Guo
New Journal of Chemistry 2007 vol. 31(Issue 3) pp:357-362
Publication Date(Web):23 Jan 2007
DOI:10.1039/B616451J
A cresolic oxygen bridging ligand, 2,6-bis{[(2-hydroxybenzyl)(2-hydroxyethyl)amino]methyl}-4-methylphenol (L), has been synthesized and characterized. The coordination of ZnII ions with L gives a novel tetranuclear complex, [ZnII4(L−3H)2](ClO4)2·3.5H2O (I), which crystallizes in a triclinic system with space group P, a = 12.261(5) Å, b = 13.887(6) Å, c = 20.738(8) Å, α = 89.996(7)°, β = 88.163(7)° and γ = 85.016(7)°. The cationic core of I is formed by four ZnII cations bridged by two cresolic and four phenolic oxygen atoms from two ligands. All four ZnII centers are pentacoordinated and adopt a distorted square pyramid geometry. ESMS and 1H NMR data indicate that I is stable in solution, and the fluorescence measurement demonstrates that it has strong fluorescence at λex = 298 nm. The fluorescent complex can selectively sense the dihydrogen phosphate anion in methanol, and the binding phenomenon can be monitored via UV-vis absorption changes and fluorescence quenching effects. The potential binding mode of I with H2PO4− has been studied by ESMS and 1H NMR spectroscopy.
Co-reporter:Lin Qiu, Pengju Jiang, Weijiang He, Chao Tu, Jun Lin, Yizhi Li, Xiang Gao, Zijian Guo
Inorganica Chimica Acta 2007 Volume 360(Issue 2) pp:431-438
Publication Date(Web):1 February 2007
DOI:10.1016/j.ica.2006.07.055
We have shown previously that 8-(5′-N,N-dimethylamino-1′-naphthalene)-sulfonamidoquinoline (DANQUIN) demonstrated a remarkable selectivity and sensitivity for the Zn(II) ion. In this work, the crystal structures of DANQUIN, Cu(DANQUIN)2 and Cu(DANPY)2 (DANPY, N-2-picolyl-(5′-N,N-dimethylamino-1′-naphthalene)-sulfonamide) are reported and compared with the simulated structure of Zn(DANQUIN)2, which is important for the understanding of the factors that govern the fluorescence of DANQUIN. Free DANQUIN mainly displays the fluorescence of the dansyl group at 547 nm while the Zn(II)-DANQUIN complex mainly shows the enhanced fluorescence of aminoquinoline at 469 nm, while the emission of the dansyl group shifted to 517 nm with an almost constant intensity. This result demonstrates the advantage of this hybrid fluorescent chemosensor for Zn(II), and also makes it a potential candidate for ratiometric Zn(II) detection.Structural analysis reveals that the fluorescent property of metal complexes of DANQUIN and DANPY is mainly determined by the nature of the coordinated metal center, while the coordination mode and geometry of the metal complexes has no evident effects. The fluorescence of the Zn(DANQUIN)2 is mainly arisen from the aminoquinoline moiety.
Co-reporter:Damin Fan;Xiaoliang Yang;Xiaoyong Wang
JBIC Journal of Biological Inorganic Chemistry 2007 Volume 12( Issue 5) pp:655-665
Publication Date(Web):2007 June
DOI:10.1007/s00775-007-0214-1
Multinuclear Pt(II) complexes represent a novel class of antitumor agents. In this work, a dinuclear monofunctional Pt(II) complex {[cis-Pt(NH3)2Cl]2(4,4′-methylenedianiline)}(NO3)2 (1) was synthesized and characterized by 1H NMR, electrospray mass spectrometry, and elemental analysis. The 2D [1H,15N] heteronuclear single quantum coherence NMR spectra of 15N-labeled 1 revealed that the cationic core of this water-soluble complex hardly hydrolyzes in aqueous solution and reacts very slowly with glutathione. Hydrolysis appears not to be an essential step for the formation of Pt–guanosine-5′-monophosphate (5′-GMP) or Pt–DNA adducts because the complex can react readily with 5′-GMP and partially transform B-DNA into its Z form. Such properties are desired to achieve the goal of enhancing cytotoxicity and lowering side effects of Pt(II) complexes. In fact, complex 1 is highly cytotoxic against the murine leukemia (P-388) and the human non-small-cell lung cancer (A-549) cell lines, and it is more cytotoxic than cisplatin at most concentrations tested.
Co-reporter:Yongmei Zhao, Weijiang He, Pengfei Shi, Jianhui Zhu, Lin Qiu, Liping Lin and Zijian Guo
Dalton Transactions 2006 (Issue 22) pp:2617-2619
Publication Date(Web):27 Mar 2006
DOI:10.1039/B601739H
A trinuclear 3N-chelated monofunctional platinum complex, [Pt3(HPTAB)Cl3](ClO4)3 (HPTAB = N,N,N′,N′,N″,N″-hexakis(2-pyridylmethyl)-1,3,5-tris(aminomethyl)benzene), has been structurally characterized, which binds to DNA and demonstrates much higher potency against the murine leukemia cell line (P-388) and the human nonsmall-cell lung cancer cell line (A-549) than cisplatin.
Co-reporter:Xiaoliang Yang, Yang Sun, Qiang Xu and Zijian Guo
Organic & Biomolecular Chemistry 2006 vol. 4(Issue 12) pp:2483-2491
Publication Date(Web):2006/06/08
DOI:10.1039/B604521A
Astilbin, a flavonoid isolated from different plants, shows diverse biological activities. This paper reports the synthesis and immunosuppressive activity of seven analogues of astilbin, which may shed light on the structure–activity relationship of the compounds. The following glycosyl flavonoids, 6-α-L-rhamnopyranosyloxyflavanone (20), 3-α-L-rhamnopyranosyloxyflavone (22), 3-α-L-rhamnopyranosyloxyflavanone (24), 3-α-L-rhamnopyranosyloxychromanone (26), 4-α-L-rhamnopyranosyloxychromanol (27), 7-hydroxy-3-α-L-rhamnopyranosyloxyflavanone (30) and 4′-hydroxy-3-α-L-rhamnopyranosyloxyflavanone (32) were prepared respectively by glycosylation of 6-hydroxyflavanone (1), 3-hydroxyflavone (2), 3-hydroxyflavanone (5), 3-hydroxychromanone (8), 4-chromanol (9), 7-benzyloxy-3-hydroxyflavanone (12), 4′-benzyloxy-3-hydroxyflavanone (15). Among them, compounds 5, 8, 12 and 15 were synthesized from flavanone (3), 4-chromanone (6), 7-hydroxyflavanone (10) and 4′-hydroxyflavanone (13) respectively. Similar to astilbin (4), compounds 22, 24, 26, 30 and 32 significantly inhibited the single mixed lymphocytes reaction (sMLR) and enhanced the apoptosis of spleen cells isolated from mice with sheep red blood cell-induced delayed-type hypersensitivity respectively. However, compound 20 only showed a slight tendency to inhibit sMLR at higher concentration. Both compounds 20 and 27 did not influence the cell apoptosis. These data suggest that the following factors play essential roles in determining the biological activity of the flavonoids: the position at which the sugar is linked to the flavone, the presence of carbonyl on C-4 and phenol hydroxyl group in A or B ring. However, the presence of a B ring is unfavorable for the biological activity and the double bond at C(2)–C(3) in C-ring shows little effect on the activity.
Co-reporter:Pengfei Shi, Qin Jiang, Jun Lin, Yongmei Zhao, Liping Lin, Zijian Guo
Journal of Inorganic Biochemistry 2006 Volume 100(5–6) pp:939-945
Publication Date(Web):May 2006
DOI:10.1016/j.jinorgbio.2005.12.020
Two gold(III) compounds [Au(TACN)Cl2]Cl (1) and [Au(TACN)Cl2][AuCl4] (2) (where TACN = 1,4,7-triazacyclononane), have been synthesized and characterized by electrospray ionization mass spectrometry (ESI-MS), 1H NMR spectroscopy and elemental analyses. The structure of compound 2 was determined by X-ray crystallography, in which TACN coordinates to the gold(III) center in a bidentate mode and the unbound amine group forms a very short intramolecular Au–H(–N) contact (1.91 Å). Biological activity data showed that compound 1 is more cytotoxic than cisplatin against A-549 and HCT-116 tumor cell lines. The interactions of compound 1 with CT-DNA were studied by UV–Vis, fluorescence and CD spectroscopy, which suggests that compound 1 can induce the distortion of DNA double helix.
Co-reporter:Yongmei Zhao;Jianhui Zhu;Weijiang He Dr.;Zhen Yang;Yangguang Zhu;Yizhi Li Dr.;Junfeng Zhang Dr. Dr.
Chemistry - A European Journal 2006 Volume 12(Issue 25) pp:
Publication Date(Web):6 JUN 2006
DOI:10.1002/chem.200600044
Polynuclear copper complexes with two or three Cu(BPA) (BPA, bis(2-pyridylmethyl)amine) motifs, [Cu2(mTPXA)Cl4]⋅3 H2O (1), [Cu2(pTPXA)Cl4]⋅3 H2O (2), [Cu3(HPTAB)Cl5]Cl⋅3 H2O (3) (mTPXA = N,N,N′,N′-tetra-(2-pyridylmethyl)-m-xylylene diamine; pTPXA = N,N, N′,N′-tetra-(2-pyridylmethyl)-p-xylylenediamine; HPTAB = N,N,N′,N′,N′′,N′′-hexakis(2-pyridylmethyl)-1,3,5-tris-(aminomethyl)benzene) have been synthesized and characterized. The crystal structures of compounds 2 and 3 showed each Cu(BPA) motif had a 4+1 square-pyramidal coordination environment with one chloride occupying the apical position and three N atoms from the same BPA moiety together with another Cl atom forming the basal plane. Fluorescence and circular dichroism (CD) spectroscopy studies indicated that the DNA binding followed an order of 3>2>1 in the compounds. These complexes cleave plasmid pUC19 DNA by using an oxidative mechanism with mercaptopropionic acid (MPA) as the reductant under aerobic conditions. Dinuclear Cu2+ complexes 1 and 2 showed much higher cleavage efficiency than their mononuclear analogue [Cu(bpa)Cl2] at the same [Cu2+] concentration, suggesting a synergistic effect of the Cu2+ centers. Moreover, the meta-dicopper centers in complex 1 facilitated the formation of linear DNA. Interestingly, the additional copper center to the meta-dicopper motif in complex 3 decreased the cleavage efficacy of meta-dicopper motif in complex 1, although it is able to cleave DNA to the linear form at higher [Cu2+] concentrations. Therefore, the higher DNA binding ability of complex 3 did not lead to higher cleavage efficiency. These findings have been correlated to the DNA binding mode and the ability of the Cu2+ complexes to activate oxygen (O2). This work is a good example of the rational design of multinuclear Cu2+ artificial nuclease and the activity of which can be manipulated by the geometry and the number of metal centers.
Co-reporter:Ying Shao, Junyong Zhang, Chao Tu, Chunhui Dai, Qiang Xu, Zijian Guo
Journal of Inorganic Biochemistry 2005 Volume 99(Issue 7) pp:1490-1496
Publication Date(Web):July 2005
DOI:10.1016/j.jinorgbio.2005.04.007
Three copper(II) complexes of aminoquinoline derivatives, l-glycine-N′-8-quinolylamide (L1), l-alanine-N′-8-quinolylamide (L2), and N-(8-quinolyl) pyridine-2-carboxamide (L3) have been shown to cleave plasmid DNA pBR322 and pUC18 with or without the presence of H2O2/ascorbate. Crystallographic data reveal that the Cu(II) coordination plane in [Cu(L1)(Ac)(H2O)] (1) and [Cu(L2)(Ac)] (2) is nearly co-planar with the quinoline ring. The cleavage activity follows the order of complex 1 > complex 2 > complex 3, which is in agreement with the reverse order of the steric hindrance of the amino-substituent of the ligands. The presence of the standard radical scavengers does not have a clear effect on the cleavage efficiency of the Cu(II) complexes, suggesting the reactive species leading to DNA damage could be DNA-bound copper-centered radicals rather than the free diffusible ones.
Co-reporter:Shouchun Zhang, Yangguang Zhu, Chao Tu, Haiying Wei, Zhen Yang, Liping Lin, Jian Ding, Junfeng Zhang, Zijian Guo
Journal of Inorganic Biochemistry 2004 Volume 98(Issue 12) pp:2099-2106
Publication Date(Web):December 2004
DOI:10.1016/j.jinorgbio.2004.09.014
A novel ternary copper(II) complex, [Cu(phen)(l-Thr)(H2O)](ClO4) (phen = 1,10-phenanthroline, l-Thr = l-threonine), has been synthesized and structurally characterized. The complex crystallized in a triclinic system with space group P1¯, a = 7.526(15) Å, b = 11.651(2) Å, c = 12.127(2) Å, α = 115.41(3)°, β = 102.34(3)° and γ = 91.33(3)°. The copper(II) center is situated in a distorted square-pyramidal geometry. At a concentration of 10−6 mol L−1, the complex exhibited potent cytotoxic effects against human leukemia cell line HL-60 and human stomach cancer cell line SGC-7901 with inhibition rates of over 90%, however, less pronounced effects were observed for human liver carcinoma cell line BEL-7402 and human non-small-cell lung cancer cell line A-549. The complex was shown to bind DNA by intercalation and cleave pBR322 DNA in the presence of ascorbate.
Co-reporter:Shouchun Zhang;Chao Tu;Xiongyong Wang;Zhen Yang;Junyong Zhang;Liping Lin;Jian Ding
European Journal of Inorganic Chemistry 2004 Volume 2004(Issue 20) pp:
Publication Date(Web):12 AUG 2004
DOI:10.1002/ejic.200400357
Two novel CuII complexes [Cu(CMQA)(H2O)] (1) (CMQA = N-carboxymethyl-L-methionine-N′-8-quinolylamide) and [Cu(MQA)(OAc)] (2) (MQA = L-methionine-N′-8-quinolylamide, OAc = CH3COO−) have been synthesized and structurally characterized. Complex 1 crystallizes in the orthorhombic system with space group P212121 [a = 5.556(1) Å, b = 15.002(3) Å, c = 20.886(4) Å] while complex 2 crystallizes in the monoclinic system with space group C2 [a = 28.463(6) Å, b = 5.264(1) Å, c = 13.345(3) Å, β = 109.142(3)°]. In both complexes the CuII center is coordinated by three N atoms of the ligand and one O atom of H2O (1) or OAc (2). The in vitro cytotoxicity of both complexes and their corresponding ligands have been tested against the murine leukemia P-388 and lung adenocarcinoma A-549 cell lines. Complex 2 shows a potent activity against both cell lines with an inhibitory rate of 100% for the murine leukemia P-388 cell line and 93.4% for the lung adenocarcinoma A-549 cell line at a concentration of 10−6 mol·L−1, while complex 1 shows only a marginal activity against the same cell lines. The reactivity of the two complexes towards γ-glutathione (GSH) has been investigated and is discussed in association with their different cytotoxicity. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Co-reporter:Qin Liu, Xiaoyong Wang, Xiaoliang Yang, Xiao Liang, Zijian Guo
Journal of Inorganic Biochemistry (November 2010) Volume 104(Issue 11) pp:1178-1184
Publication Date(Web):1 November 2010
DOI:10.1016/j.jinorgbio.2010.07.007
Platinum-based anticancer drugs such as cisplatin induce increased oxidative stress and oxidative damage of DNA and other cellular components, while selenium plays an important role in the antioxidant defense system. In this study, the interaction between a platinum(II) methionine (Met) complex [Pt(Met)Cl2] and a diselenide compound selenocystine [(Sec)2] was studied by electrospray ionization mass spectrometry, high performance liquid chromatography mass spectrometry, and 1H NMR spectroscopy. The results demonstrate that the diselenide bond in (Sec)2 can readily and quickly be cleaved by the platinum complex. Formation of the selenocysteine (Sec) bridged dinuclear complex [Pt2(Met-S,N)2(μ-Sec-Se,Cl)]3+ and Sec chelated species [Pt(Met-S,N)(Sec-Se,N)]2+ was identified at neutral and acidic media, which seems to result from the intermediate [Pt(Met-S,N)(Sec-Se)Cl]+. An accelerated formation of S–Se and S–S bonds was also observed when (Sec)2 reacted with excessive glutathione in the presence of [Pt(Met)Cl2]. These results imply that the mechanism of activity and toxicity of platinum drugs may be related to their fast reaction with seleno-containing biomolecules, and the chemoprotective property of selenium agents against cisplatin-induced toxicity could also be connected with such reactions.Diselenide can be readily cleaved by platinum complex, which may relate to the therapeutic and protective mechanism of platinum drugs.Download full-size image
Co-reporter:Ruimin Xing, Xiaoyong Wang, Changli Zhang, Yangmiao Zhang, Qi Wang, Zhen Yang, Zijian Guo
Journal of Inorganic Biochemistry (July 2009) Volume 103(Issue 7) pp:1039-1044
Publication Date(Web):1 July 2009
DOI:10.1016/j.jinorgbio.2009.05.001
Clinical application of platinum-based anticancer drugs is largely limited by severe general toxicity and drug resistance. Drug delivery systems with tumor-targeting potential are highly desired for improving the efficacy and applicability of these drugs. This study describes an alternative strategy for the delivery of platinum drugs (cisplatin, carboplatin and oxaliplatin) by encapsulating each of them in the cavity of apoferritin (AFt). The encapsulation was achieved through manipulating the pH-dependent unfolding–refolding process of AFt at pH 2.0 and 7.4, respectively, in saturated drug solution. UV–vis spectrometry, circular dichroism spectrometry, dynamic light scattering, and inductively coupled plasma mass spectrometry were used to characterize the AFt–drug complexes. The loading capacity of AFt varies with respective drugs and the structural integrity of the protein shell remains intact after encapsulation. In vitro assays on the rat pheochromocytoma cell line (PC12) show that AFt–cisplatin inhibits the cells in a slow but sustaining mode and the cellular uptake of platinum is enhanced by AFt. AFt–carboplatin and AFt–oxaliplatin complexes only exhibit a marginal cytotoxicity towards this cell line under similar concentrations.
Co-reporter:Yang Jiao, Jianping Zhu, Yan Guo, Weijiang He and Zijian Guo
Journal of Materials Chemistry A 2017 - vol. 5(Issue 21) pp:NaN5222-5222
Publication Date(Web):2017/05/05
DOI:10.1039/C7TC00507E
A simple spin crossover (SCO) complex, [Fe(bpp)2][BF4]2 (bpp = 2,6-bis(pyrazol-1-yl)pyridine), was found to exhibit luminesce with a broad band from 425 to 565 nm in the solid state at ambient temperature, although it was non-luminescent at <250 K. In addition, an abrupt enhancement in luminescence was found at ∼260 K, which is exactly the temperature for a transition from the low spin (LS) to the high spin (HS) state of the complex. This implied that the luminescence was triggered by the thermal spin transition from the LS to HS state, which was different from the emission quenching effect of a normal paramagnetic metal center. A theoretical study via DFT calculations suggested that the excitation efficiency of the complex from the ground state to the lowest excited state for the HS state was higher than that for the LS state, which was proposed to be the reason for the HS-triggered luminescence. A hole/electron excitation analysis and orbital component analysis demonstrated that metal to ligand charge transfer (MLCT) upon excitation was responsible for the luminescence of this complex. This is the first report about the MLCT luminescence of SCO Fe(II) complex tuned by the thermal spin transition. Although the HS-triggered luminescence of solid [Fe(bpp)2][BF4]2 was very weak and not suitable for practical applications, molecular materials for both the multiple readout application and magnetism-regulated optical signaling could be anticipated by improving the luminescence efficiency of this type of SCO complexes in the future.
Co-reporter:Huachao Chen, Jiangwei Tian, Danyang Liu, Weijiang He and Zijian Guo
Journal of Materials Chemistry A 2017 - vol. 5(Issue 5) pp:NaN979-979
Publication Date(Web):2016/12/29
DOI:10.1039/C6TB02714H
A smart dendrigraft poly-L-lysine (DGL) nanoplatform for mitochondria-targeted chemotherapy was devised, which aims to achieve enhanced efficacy against drug resistant tumor cells. In this system, doxorubicin (Dox) was intercalated into the DNA duplex containing an ATP aptamer, which was subsequently condensed by DGL to form a nanoscaled controlled-release system. A nucleolin-specific binding aptamer, AS1411, and a cytochrome c aptamer were then incorporated into the system to give the nanoparticles (Dox/Mito-DGL) for biological evaluations. This dual modified system has been shown to selectively accumulate in the mitochondria of cancer cells and promptly release the loaded Dox in virtue of the high concentrations of ATP in mitochondria. The mitochondria-specific and spatiotemporally controlled release of Dox led to enhanced therapeutic outcomes both in vitro and in vivo. More significantly, Dox/Mito-DGL was successfully applied to improve the efficacy towards multi-drug resistant cancer cells by altering the mitochondrial membrane potential and bypassing the P-glycoprotein-mediated drug efflux. This work presents a paradigm for mitochondria-targeting therapy against mitochondria-associated diseases and provides a potential avenue for overcoming MDR in the treatment of solid tumors.
Co-reporter:Zhipeng Liu, Weijiang He and Zijian Guo
Chemical Society Reviews 2013 - vol. 42(Issue 4) pp:NaN1600-1600
Publication Date(Web):2013/01/18
DOI:10.1039/C2CS35363F
Coordination chemistry plays an essential role in the design of photoluminescent probes for metal ions. Metal coordination to organic dyes induces distinct optical responses which signal the presence of metal species of interest. Luminescent lanthanide (Ln3+) and transition metal complexes of d6, d8 and d10 configurations often exhibit unique luminescence properties different from organic dyes, such as high quantum yield, large Stokes shift, long emission wavelength and emission lifetimes, low sensitivity to microenvironments, and can be explored as lumophores to construct probes for metal ions, anions and neutral species. In this review, the design principles and coordination chemistry of metal probes based on mechanisms of PeT, PCT, ESIPT, FRET, and excimer formation will be discussed in detail. Particular attention will be given to rationales for the design of turn-on and ratiometric probes. Moreover, phosphorescent probe design based on Ln3+ and d6, d8 and d10-metal complexes are also presented via discussing certain factors affecting the phosphorescence of these metal complexes. A survey of the latest progress in photoluminescent probes for identification of essential metal cations in the human body or toxic metal cations in the environment will be presented focusing on their design rationales and sensing behaviors. Metal complex-based photoluminescent probes for biorelated anions such as PPi, and neutral biomolecules ATP, NO, and H2S will be discussed also in the context of their metal coordination-related sensing behaviors and design approaches.
Co-reporter:Xiaoyong Wang and Zijian Guo
Chemical Society Reviews 2013 - vol. 42(Issue 1) pp:NaN224-224
Publication Date(Web):2012/10/05
DOI:10.1039/C2CS35259A
Platinum-based anticancer drugs occupy a crucial role in the treatment of various malignant tumours. However, the efficacy and applicability of platinum drugs are heavily restricted by severe systemic toxicities and drug resistance. Different drug targeting and delivery (DTD) strategies have been developed to prevent the shortcomings of platinum-based chemotherapy. These approaches can be roughly categorized into two groups; namely, active and passive tactics. Active DTD is realized through specific molecular interactions between the drugs and cell or tissue elements, while passive DTD is achieved by exploiting the enhanced permeability and retention effect in tumour tissues. The principal methods for active DTD include conjugation of platinum drugs with selective targeting moieties or encapsulation of platinum drugs in host molecules. Bioactive substances such as hormones, carbohydrates, bisphosphonates, peptides and proteins are commonly used in active DTD. Passive DTD generally involves the fabrication of functionalized polymers or nanoparticles and the subsequent conjugation of platinum drugs with such entities. Polymeric micelles, liposomes, nanotubes and nanoparticles are frequently used in passive DTD. In some cases, both active and passive mechanisms are involved in one DTD system. This review concentrates on various targeting and delivery techniques for improving the efficacy and reducing the side effects of platinum-based anticancer drugs. The content covers most of the related literatures published since 2006. These innovative tactics represent current state-of-the-art developments in platinum-based anticancer drugs.
Co-reporter:Xiaohui Wang, Xiaoyong Wang, Changli Zhang, Yang Jiao and Zijian Guo
Chemical Science (2010-Present) 2012 - vol. 3(Issue 4) pp:NaN1312-1312
Publication Date(Web):2012/01/26
DOI:10.1039/C2SC01100J
Alzheimer's disease (AD) is a neurodegenerative illness associated with amyloid β-peptide (Aβ) aggregation in the brain. Aβ shows high affinity for metal ions such as Zn2+ and Cu2+, which constitutes the major reason for the Aβ aggregation and related neurotoxicity. Metal chelators are potential therapeutic agents for AD because they could sequester metal ions from the Aβ aggregates and reverse the aggregation. In this study, two macrocyclic platiniferous chelators (PC1, PC2) with cyclen as the metal-chelating unit and Pt(bipyridine)Cl2 as the Aβ-binding unit have been designed as novel bifunctional inhibitors of the metal-induced Aβ aggregation. The interactions between the chelators and Aβ40 aggregates are studied by tandem mass spectrometry and 1H NMR. The platinum centers in PC1 and PC2 are shown to coordinate with histidine residues (His-14 or -13) of Aβ40. The inhibitory effect of the chelators on Aβ40 aggregation induced by Zn2+ and Cu2+ ions is investigated using turbidimetry, a BCA protein assay, and transmission electron microscopy. PC1 and PC2 show significant inhibition against the Aβ aggregation and the action is more effective than that exerted by cyclen. By contrast, the corresponding anticancer drug cisplatin exhibits no inhibition against the Aβ aggregation. PC1 and PC2 can also suppress the Cu-Aβ40 mediated generation of reactive oxygen species and their corresponding neurotoxicity in cortical neuronal cells of mice, and reduce the extent of Aβ aggregation in the brain homogenates of transgenic mice. These chelators may work through simultaneous metal chelation and peptide modification to interfere with the Aβ aggregation. Such an intramolecular synergism distinguishes PC1 and PC2 from other chelators as potential anti-AD agents.
Co-reporter:Xiaohui Wang, Xiaoyong Wang, Shanshan Cui, Yan Wang, Guangju Chen and Zijian Guo
Chemical Science (2010-Present) 2013 - vol. 4(Issue 9) pp:NaN3752-3752
Publication Date(Web):2013/07/16
DOI:10.1039/C3SC51781K
Recognition of DNA depurination is of great importance for early cancer detection. Current analytical methods for this purpose are usually complicated. Luminescent lanthanide complexes possess some fascinating optical properties that have shown potential applications in biomedical research. In this study, a novel terbium(III) complex (TbL) has been demonstrated to be capable of recognizing purine nucleobases in DNA as a selective time-resolved luminescence probe. TbL consists of a luminescent terbium(III) center and two nitroimidazole groups linked by a linear polydentate ligand. The luminescence of TbL is enhanced remarkably upon reaction with oligonucleotides or natural DNA containing purine bases in aqueous solution, while it is quenched dramatically as depurination occurs to DNA. Mechanistic studies using circular dichroism and fluorescence spectroscopies reveal that the luminescence enhancement results from the preferential intercalation between the nitroimidazole moieties of TbL and the purine bases of DNA, which regulate the electron withdrawing effect of nitro groups via hydrogen bonds and thereby affect the energy transfer from the ligand to the metal center of the probe. This mechanism is also supported by molecular dynamics simulation results for the reaction. The distinct luminescence responses of TbL in the presence and absence of purine bases in DNA make it a sensitive probe for DNA depurination in physiological conditions.
Co-reporter:Wen Zhou, Xiaoyong Wang, Ming Hu, Chengcheng Zhu and Zijian Guo
Chemical Science (2010-Present) 2014 - vol. 5(Issue 7) pp:NaN2770-2770
Publication Date(Web):2014/03/11
DOI:10.1039/C4SC00384E
Copper complexes are potential anticancer drugs by virtue of their available redox properties and low toxicity. In this study, a copper(II) complex, [Cu(ttpy-tpp)Br2]Br (simplified as CTB, ttpy-tpp = 4′-p-tolyl-(2,2′:6′,2′′-terpyridyl)triphenylphosphonium bromide), is synthesized and characterized by X-ray crystallography and ESI-MS as a targeted anticancer agent. Triphenylphosphine (TPP) is introduced into the complex for its mitochondrion-targeting ability and lipophilic character. The uptake of CTB by tumor cells and mitochondria was determined by ICP-MS or fluorescence spectrometry. CTB is able to cross the cytoplasmic and mitochondrial membranes of tumor cells and influence the mitochondrial membrane potential more profoundly than the anticancer drug cisplatin. The cytotoxicity of CTB was tested on MCF-7, HeLa, Skov-3, A549 and cisplatin-resistant A549R tumor cells by MTT assay. CTB is more cytotoxic against these cells than cisplatin; particularly, it is highly effective against cisplatin-resistant tumor cells. The interaction between CTB and DNA has been studied by spectroscopic methods and agarose gel electrophoresis. CTB strongly interacts with DNA via intercalation stabilized by electrostatic forces, and displays a significant cleavage activity towards supercoiled pBR322 DNA and cellular DNA through an oxidative mechanism. The cytotoxicity of CTB seems to result from multiple mechanisms of action, including the modification of DNA conformation, generation of reactive oxygen species, scission of DNA strands, and dissipation of mitochondrial membrane potential. The delocalized cationic property and high hydrophilicity of CTB favours its selective accumulation in cancer cells and mitochondria. This study demonstrates that copper complexes with mitochondrion-targeting function could be efficient anticancer drugs immune to the drug resistance of cisplatin.
Co-reporter:Zhipeng Liu, Changli Zhang, Weijiang He, Zhenghao Yang, Xiang Gao and Zijian Guo
Chemical Communications 2010 - vol. 46(Issue 33) pp:NaN6140-6140
Publication Date(Web):2010/07/28
DOI:10.1039/C0CC00662A
A ratiometric fluorescent Cd2+ sensor DBITA which featured the Cd2+-induced red-shift of emission (53 nm) and picomolar sensitivity in both aqueous media and living cells was developed.
Co-reporter:Jiafei Mao, Yangmiao Zhang, Jianhui Zhu, Changli Zhang and Zijian Guo
Chemical Communications 2009(Issue 8) pp:NaN910-910
Publication Date(Web):2009/01/19
DOI:10.1039/B817968A
The combination of a red light PDT agent and a Pt(II)-based chemotherapeutic drug at the molecular level maintains the intrinsic functions of each unit; the conjugated complexes exhibit remarkable photocytoxicity and demonstrate potential to serve as agents for DNA-targeting PDT as well as red light photochemotherapy.
Co-reporter:Zhipeng Liu, Changli Zhang, Yuncong Chen, Fang Qian, Yang Bai, Weijiang He and Zijian Guo
Chemical Communications 2014 - vol. 50(Issue 10) pp:NaN1255-1255
Publication Date(Web):2013/11/26
DOI:10.1039/C3CC46262E
A visible light excitable ratiometric Zn2+ sensor was developed by integrating a Zn2+ chelator as the ICT donor of the fluorophore sulfamoylbenzoxadiazole, which displays the Zn2+-induced hypsochromic emission shift (40 nm) and favors the in vivo ratiometric Zn2+ imaging in zebrafish larvae.
Co-reporter:Huachao Chen, Weijiang He and Zijian Guo
Chemical Communications 2014 - vol. 50(Issue 68) pp:NaN9717-9717
Publication Date(Web):2014/06/25
DOI:10.1039/C4CC03385J
Synergistic release of platinum anticancer drugs and O2 can be achieved in an H2O2-responsive nanocarrier incorporated with catalase. Such a system combines the advantages of chemotherapy and oxygen therapy and demonstrated improved therapeutic efficacy against cisplatin resistant cell lines which often appear to be in hypoxia.
Co-reporter:Mingmin Wu, Xiaoyong Wang, Kun Wang and Zijian Guo
Chemical Communications 2016 - vol. 52(Issue 54) pp:NaN8380-8380
Publication Date(Web):2016/06/07
DOI:10.1039/C6CC02674E
A general detection method for DNA methylation is developed based on the FRET mechanism between upconversion nanoparticles and gold nanorods, which can recognize the cytosine methylation in a known DNA strand at a concentration as low as 7 pM.
Co-reporter:Yafeng He, Jian Yuan, Yuchen Qiao, Dan Wang, Weizhong Chen, Xichun Liu, Hao Chen and Zijian Guo
Chemical Communications 2015 - vol. 51(Issue 74) pp:NaN14067-14067
Publication Date(Web):2015/07/29
DOI:10.1039/C5CC05257B
In order to systematically investigate the influence of carrier ligands on the interaction of Pt–DNA adducts with damage recognition proteins, a series of DNA probes containing 1,2-GG platinum compound crosslinks using cisplatin, oxaliplatin, (S,S-DACH)PtCl2 and (cis-1,4-DACH)PtCl2 (kiteplatin) has been constructed. These complexes share similar DNA binding properties although they exhibit quite different cytotoxicity. It is revealed that HMGB1 (high-mobility group protein B1) was the most commonly found protein that recognizes all Pt(II)-DNA probes and prefers cisplatin–DNA probes more than the others. Interestingly, an important component of the replication protein A complex, RPA2, was found to bind to kiteplatin much more tightly than other proteins. These results may be important for the interpretation of the roles of carrier ligands in platinum(II)-based anticancer complexes.
Co-reporter:Changli Zhang, Zhipeng Liu, Yunling Li, Weijiang He, Xiang Gao and Zijian Guo
Chemical Communications 2013 - vol. 49(Issue 97) pp:NaN11432-11432
Publication Date(Web):2013/10/15
DOI:10.1039/C3CC46862C
A newly developed fluorescent sensor, Naph-BPEA, shows a specific turn-on response to Zn2+ and can be excited by visible light. The in situ nuclear Zn2+ imaging in HeLa and HepG2 cells reveals the nuclear envelope penetrability of the sensor. The specific sensor location in a zebrafish larva was also demonstrated.
Co-reporter:Lin Qiu, Chengcheng Zhu, Huachao Chen, Ming Hu, Weijiang He and Zijian Guo
Chemical Communications 2014 - vol. 50(Issue 35) pp:NaN4634-4634
Publication Date(Web):2014/03/11
DOI:10.1039/C3CC49482A
Integrating N2-hydroxyethyldiethylenetriamine with anthracene gives a [2+2] macrocycle fluorescent sensor. This sensor displays an instant/reversible turn-on response specific to Fe3+, which allows facile visualization of the Fe3+/Fe2+ transition and intracellular Fe3+ imaging.
Co-reporter:Yuncong Chen, Chengcheng Zhu, Zhenghao Yang, Jing Li, Yang Jiao, Weijiang He, Junjie Chen and Zijian Guo
Chemical Communications 2012 - vol. 48(Issue 42) pp:NaN5096-5096
Publication Date(Web):2012/03/28
DOI:10.1039/C2CC31217D
A novel sensitive and specific Hg2+ chemodosimeter, derived from 1′,3′-dithiane-substituted 2,1,3-benzoxadiazole, displays “turn-on” fluorescent and colorimetric responses via an Hg2+-triggered aldehyde recovery reaction. Its potential to monitor Hg2+ in living organisms has been demonstrated using zebrafish larvae.
Co-reporter:Jinzhuan Wang, Xiaoyong Wang, Yajie Song, Chengcheng Zhu, Jing Wang, Kun Wang and Zijian Guo
Chemical Communications 2013 - vol. 49(Issue 27) pp:NaN2788-2788
Publication Date(Web):2013/02/12
DOI:10.1039/C3CC39059D
Rhodamine-embedded maghemite nanoparticles could act as fluorescent drug carriers to track and transport platinum anticancer drugs simultaneously.
Co-reporter:Yuncong Chen, Chengcheng Zhu, Jiajie Cen, Jing Li, Weijiang He, Yang Jiao and Zijian Guo
Chemical Communications 2013 - vol. 49(Issue 69) pp:NaN7634-7634
Publication Date(Web):2013/06/24
DOI:10.1039/C3CC42959H
ICT fluorophore benzoxadiazole with its electron-donating group modified as a Cu2+ chelator was conjugated with coumarin to construct a new ratiometric sensor with reversible intracellular Cu2+ imaging ability.
Co-reporter:Xiaohui Wang, Xiaoyong Wang, Yanqing Wang and Zijian Guo
Chemical Communications 2011 - vol. 47(Issue 28) pp:NaN8129-8129
Publication Date(Web):2011/06/20
DOI:10.1039/C1CC12429C
A terbium(III) complex gives off strong luminescence upon reacting with human serum albumin in aqueous solution, which can be used to detect the presence and structural modifications of this protein.
Co-reporter:Zhipeng Liu, Changli Zhang, Yuncong Chen, Weijiang He and Zijian Guo
Chemical Communications 2012 - vol. 48(Issue 67) pp:NaN8367-8367
Publication Date(Web):2012/07/02
DOI:10.1039/C2CC33648K
A mitochondria-targeted fluorescent sensor (Mito-ST), constructed by integrating a sulfamoylbenzoxadiazole fluorophore with a phosphonium group, displays the specific Zn2+-induced hypsochromic shifts of both excitation (69 nm) and emission (35 nm) maxima. Its ratiometric Zn2+ imaging ability via dual excitation mode has been applied in MCF-7 cells to clarify the different behaviours of mitochondrial Zn2+ release stimulated by H2O2 and SNOC.
Co-reporter:Zuqin Xue, Miaoxin Lin, Jianhui Zhu, Junfeng Zhang, Yizhi Li and Zijian Guo
Chemical Communications 2010 - vol. 46(Issue 8) pp:NaN1214-1214
Publication Date(Web):2010/01/16
DOI:10.1039/B922222G
Platinum(II) complexes bearing geminal bisphosphonate moieties have excellent solubility in both organic and aqueous solutions and show considerable cytotoxicity against human osteosarcoma (MG-63) and ovarian cancer (COC1) cell lines with different apoptotic pathways from that of cisplatin.
Co-reporter:Yafeng He, Yin Ding, Dan Wang, Wanjun Zhang, Weizhong Chen, Xichun Liu, Weijie Qin, Xiaohong Qian, Hao Chen and Zijian Guo
Chemical Science (2010-Present) 2015 - vol. 6(Issue 3) pp:NaN2078-2078
Publication Date(Web):2014/12/15
DOI:10.1039/C4SC03650F
Cisplatin, one of the most effective anticancer drugs, is a DNA-damaging agent that induces cell death primarily by apoptosis. For many years, HMGB1 has been known to be a recognition protein for cisplatin–DNA lesions. Here, an application of a biomolecular probe based on a peptide–oligonucleotide conjugate is presented as a novel method for investigating this recognition process in vivo. Proteins known to be involved in the recognition of cisplatin-damaged DNA were pulled down and identified, including members of the HMGB family and a number of other proteins. Interestingly, at least 4 subforms of HMGB1 bind to cisplatin–DNA adducts. These proteins were further identified as post-translationally acetylated or phosphorylated forms of HMGB1. These results provide a rich pool of protein candidates whose roles in the mechanism of action of platinum drugs should be explored. These newly discovered molecular components of the DNA damage signalling cascade could serve as novel links between the initial cell responses to DNA damage and the downstream apoptotic or DNA repair pathways.
Co-reporter:Zhen Yang, Xiaoyong Wang, Huajia Diao, Junfeng Zhang, Hongyan Li, Hongzhe Sun and Zijian Guo
Chemical Communications 2007(Issue 33) pp:NaN3455-3455
Publication Date(Web):2007/05/17
DOI:10.1039/B705326F
Apoferritin derived from the native protein ferritin was employed to encapsulate anticancer drugs cisplatin and carboplatin.
Co-reporter:Zhenzhu Zhu, Zenghui Wang, Yigang Hao, Chengcheng Zhu, Yang Jiao, Huachao Chen, Yun-Ming Wang, Jun Yan, Zijian Guo and Xiaoyong Wang
Chemical Science (2010-Present) 2016 - vol. 7(Issue 4) pp:
Publication Date(Web):
DOI:10.1039/C5SC04049C
Co-reporter:Yuncong Chen, Chengcheng Zhu, Jiajie Cen, Yang Bai, Weijiang He and Zijian Guo
Chemical Science (2010-Present) 2015 - vol. 6(Issue 5) pp:NaN3194-3194
Publication Date(Web):2015/03/16
DOI:10.1039/C4SC04021J
The homeostasis of mitochondrial pH (pHm) is crucial in cell physiology. Developing small-molecular fluorescent sensors for the ratiometric detection of pHm fluctuation is highly demanded yet challenging. A ratiometric pH sensor, Mito-pH, was constructed by integrating a pH-sensitive FITC fluorophore with a pH-insensitive hemicyanine group. The hemicyanine group also acts as the mitochondria targeting group due to its lipophilic cationic nature. Besides its ability to target mitochondria, this sensor provides two ratiometric pH sensing modes, the dual excitation/dual emission mode (Dex/Dem) and dual excitation (Dex) mode, and its linear and reversible ratiometric response range from pH 6.15 to 8.38 makes this sensor suitable for the practical tracking of pHm fluctuation in live cells. With this sensor, stimulated pHm fluctuation has been successfully tracked in a ratiometric manner via both fluorescence imaging and flow cytometry.
Co-reporter:Nafees Muhammad, Xiaoyong Wang, Kun Wang, Chengcheng Zhu, Zhenzhu Zhu, Yang Jiao and Zijian Guo
Dalton Transactions 2016 - vol. 45(Issue 33) pp:NaN13178-13178
Publication Date(Web):2016/06/09
DOI:10.1039/C6DT01434H
Drug resistance and unfavorable pharmacokinetics are the major obstacles for conventional anticancer drugs. A combination of different anticancer drugs into one formulation is a common strategy to alleviate the side effects of individual drugs in clinical practice. Platinum anticancer drugs are the typical defective therapeutic agents for cancer chemotherapy and have poor selectivity for tumor cells. In this study, a nanosystem composed of poly(lactic-co-glycolic acid) (PLGA), PtIV prodrug (PPD) and α-tocopheryl succinate (α-TOS) was designed to overcome these defects. The PtIV prodrug, c,c,t-[Pt(NH3)2Cl2(O2CC(CH3)3)2], was prepared by the reaction of oxoplatin with trimethylacetic anhydride and its structure was characterized by X-ray crystallography. The PPD and α-TOS self-assembled with PLGA, forming a dual-drug loaded nanoparticle (DDNP). The surface of the DDNP was decorated with galactosamine (G), giving rise to a G-DDNP that can actively target the liver cancer cells through the overexpressed asialoglycoprotein receptors. The DDNPs and G-DDNPs were characterized by SEM, TEM, and DLS. They are spherical in shape with required polydispersity and suitable mean size (ca. 150 nm). The in vitro cytotoxicity of DDNPs and G-DDNPs was tested against the human SMMC-7721 liver cancer cell line. G-DDNPs are more potent than the corresponding free drugs and untargeted DDNP, showing that some synergistic and tumor-specific effects are achieved by this strategy. The results demonstrate that dual-drug loaded nanoformulations with tumor-targeting function could be effective anticancer agents for conquering the shortcomings related to single-drug chemotherapy.
Co-reporter:Jianhui Zhu, Miaoxin Lin, Damin Fan, Ziyi Wu, Yuncong Chen, Junfeng Zhang, Yi Lu and Zijian Guo
Dalton Transactions 2009(Issue 48) pp:NaN10895-10895
Publication Date(Web):2009/11/13
DOI:10.1039/B913236H
The DNA binding ability and binding mode of platinum complexes are crucial factors that govern their cytotoxic activity. In this work, circular dichroism spectroscopy, gel electrophoresis and MALDI-TOF MS spectrometry combined with enzymatic degradation have been used to elucidate the role of bridging ligands in DNA-binding ability and cross-linking patterns of two dinuclear antitumour active platinum(II) complexes, {[cis-Pt(NH3)2Cl]2L1}(NO3)2 (1, L1= 4,4′-methylenedianiline) and {[cis-Pt(NH3)2Cl]2L2}(NO3)2 (2, L2 = α,α′-diamino-p-xylene). Although both complexes have two cis-diammine-Pt(II) moieties (1,1/c,c), complex 1 exhibits much higher DNA-binding ability than complex 2. The former readily forms both 1,3- and 1,4-intrastrand cross-links with DNA oligonucleotides, while the latter preferentially forms 1,4- rather than 1,3-intrastrand cross-links. Cytotoxicity studies against a human non-small-cell lung cancer cell line (A549) demonstrate that complex 1 has higher activity than 2. These results show that the linker properties play a critical role in controlling the DNA-binding and cross-linking abilities and in modulating the cytotoxicity of dinuclear platinum complexes.
Co-reporter:Ruimin Xing, Xiaoyong Wang, Liangliang Yan, Changli Zhang, Zhen Yang, Xinghao Wang and Zijian Guo
Dalton Transactions 2009(Issue 10) pp:NaN1713-1713
Publication Date(Web):2009/01/23
DOI:10.1039/B900256C
Apoferritin-coated photoluminescent CdSe nanoparticles generated by an EDTA-mediated in situ method are photostable, water soluble and biocompatible.
Co-reporter:Guangyu Su, Zhipeng Liu, Zhijun Xie, Fang Qian, Weijiang He and Zijian Guo
Dalton Transactions 2009(Issue 38) pp:NaN7890-7890
Publication Date(Web):2009/08/24
DOI:10.1039/B914802G
Triphosphate or pyrophosphate can be recognised by a diZn2+ complex of bis(BPEA)-appended intramolecular charge transfer fluorophore 4-amino-7-aminosulfonyl-2,1,3-benzoxadiazole, displaying a 5–6 fold fluorescent enhancement at 576 nm.
Co-reporter:Ruimin Xing, Xiaoyong Wang, Changli Zhang, Jinzhuan Wang, Yangmiao Zhang, You Song and Zijian Guo
Journal of Materials Chemistry A 2011 - vol. 21(Issue 30) pp:NaN11149-11149
Publication Date(Web):2011/06/27
DOI:10.1039/C1JM11369K
Magnetic nanoparticles are promising carriers for targeted drug delivery. Superparamagnetic magnetite nanocrystal clusters modified with sodium carboxymethylcellulose were prepared by an in situ hydrothermal procedure in this study. The composition, morphology, and magnetic property of the clusters have been characterized by SEM, TEM, XRD, XPS, TGA, IR, and SQUID. The clusters display excellent dimensional uniformity, strong magnetisability, good aqueous dispersibility, and modifiable functionality. By virtue of the abundant carboxylate groups on the surface of the clusters, dechlorinated cisplatin was tethered to the superparamagnetic nanoparticles. The formation and the magnetism of the conjugate have been confirmed by zeta potential, EDX, ICP-MS, XPS, and SQUID. The magnetic property is well retained in the drug-loaded clusters. In comparison with cisplatin, the conjugate can more readily enter cancer cells and exert higher cytotoxicity towards the human cervical cancer HeLa cells and the human hepatocarcinoma HepG2 cells. These nanoparticles are likely to be used as targeted carriers to deliver platinum anticancer drugs.
Co-reporter:Qin Jiang, Zhengyi Wu, Yangmiao Zhang, Anna C. G. Hotze, Michael J. Hannon and Zijian Guo
Dalton Transactions 2008(Issue 23) pp:NaN3060-3060
Publication Date(Web):2008/04/14
DOI:10.1039/B719010G
Two novel copper(II) terpyridine complexes, [Cu(atpy)(NO3)(H2O)](NO3)·3H2O (1) and [Cu(ttpy)(NO3)2] (2) (atpy = 4′-p-N9-adeninylmethylphenyl-2,2′:6,2″-terpyridine; ttpy = 4′-p-tolyl-2,2′:6,2″-terpyridine) have been prepared and structurally characterized by X-ray crystallography. Both complexes show a CuN3O2 coordination in a square pyramidal (4 + 1) geometry with terpyridine acting as an equatorial ligand. For complex 1, intermolecular AA base pairing interaction is observed between N6 and N1 of adjacent adenines with N6⋯N1 of 3.027(7) Å. A molecular dynamics simulation of the DNA binding of two complexes showed that the adenine moiety plays an important role in the intercalation of 1 into DNA. This is verified by UV, fluorescence, circular dichroism and flow linear dichroism studies. The promotional effect from the adenine moiety to the intracellular DNA binding of complex 1 is also confirmed by the inductively coupled plasma mass (ICP-MS) spectrometry data which showed a significant higher copper content in DNA isolated from complex 1 treated MCF-7 and HeLa cells.
Co-reporter:Xiaoyong Wang and Zijian Guo
Dalton Transactions 2008(Issue 12) pp:NaN1532-1532
Publication Date(Web):2007/12/04
DOI:10.1039/B715903J
Metal complexes afford an opportunity for the discovery of new antitumour drugs with truly novel mechanisms of action. Various tactics and some new concepts have been employed to improve the physico-chemical and biological properties of metal complexes. Recent advances in this area demonstrate a bright prospect for the utilization of metal complexes in cancer chemotherapy. The theme of this article focuses on the approaches towards the rational design of platinum(II) and gold(III) complexes with antitumour properties based on the updated understanding of the mechanism of action of these compounds. The complexes summarized in this work include monofunctional platinum(II) complexes, multinuclear platinum(II) complexes, hybrid and targeted platinum(II) complexes, and gold(III) complexes. Most of them violate the established structure-activity relationships and demonstrate different reactivities from cisplatin and thereby show some potential for the prevention of detoxification.
Co-reporter:Shengde Wu, Xiaoyong Wang, Chengcheng Zhu, Yajie Song, Jing Wang, Yizhi Li and Zijian Guo
Dalton Transactions 2011 - vol. 40(Issue 40) pp:NaN10382-10382
Publication Date(Web):2011/06/17
DOI:10.1039/C1DT10555H
Two monofunctional platinum(II) complexes, cis-[PtL(NH3)2Cl]NO3 (1) and cis-[PtL′(NH3)2Cl]NO3 (2) {L = N-methyl-7-nitro-N-(2-(pyridin-2-yl)ethyl)benzo[c][1,2,5]-oxadiazol-4-amine, L′ = 7-nitro-N-(2-(pyridin-2-yl)ethyl)benzo[c][1,2,5] oxadiazol-4-amine}, have been synthesized and characterized. The X-ray single crystal structure of complex 1 shows that platinum(II) is coordinated in a square-planar geometry with a [PtN3Cl] setting. Fluorescence profiles of the complexes show that complex 1 is more suitable for cellular imaging than complex 2. The cellular uptake and distribution of complex 1 in the human cervical cancer HeLa cells were studied using confocal microscopy. Complex 1 enters the cells slowly, induces cytoplasmic vacuolations, and accumulates in the nucleoli. These results suggest that monofunctional platinum(II) complexes can stimulate tumour cells to undergo a nonapoptotic death process, which is distinct from the apoptosis induced by cisplatin.
Co-reporter:Yuncong Chen, Yang Bai, Zhong Han, Weijiang He and Zijian Guo
Chemical Society Reviews 2015 - vol. 44(Issue 14) pp:NaN4546-4546
Publication Date(Web):2015/03/09
DOI:10.1039/C5CS00005J
Zn2+ plays essential roles in various physiological processes in living systems, and the investigation of Zn2+ related physiology and pathology has attracted considerable interest. Because photoluminescence (PL) imaging possesses distinct advantages, such as high sensitivity and non-invasiveness, and excellent temporal and spatial resolution, it has become a powerful tool for the real time monitoring of Zn2+ distribution, uptake, and trafficking. Over the last two decades, great efforts have been devoted to PL Zn2+ imaging in living systems, which proved the Zn2+ fluctuations in physiological processes and the temporal-spatial distribution of labile Zn2+ as well as the localization of labile Zn2+ pools. Advances in PL techniques, such as fluorescence microscopy, confocal fluorescence microscopy, two photon fluorescence microscopy, lifetime based techniques and luminescence optical imaging systems, have made remarkable contributions in tackling major challenges in Zn2+ PL imaging. With the rational design and proper use of fluorescent sensors, Zn2+ imaging in various cell lines, organelles, tissues, organs and living animals has been realized, which was shown to be crucial in elucidating the biological and physiological roles of labile Zn2+.
Co-reporter:Jinzhuan Wang, Xiaoyong Wang, Yajie Song, Jing Wang, Changli Zhang, Cunjie Chang, Jun Yan, Lin Qiu, Mingmin Wu and Zijian Guo
Chemical Science (2010-Present) 2013 - vol. 4(Issue 6) pp:NaN2612-2612
Publication Date(Web):2013/04/15
DOI:10.1039/C3SC50554E
Superparamagnetic iron oxide nanoparticles (SPION) are potential drug carriers and a magnetic resonance imaging (MRI) contrast agent for cancer therapy and diagnosis. In this study, dechlorinated cisplatin (CMDP) is tethered to maghemite nanoparticles modified with 4-oxo-4-(3-(triethoxysilyl)propylamino)butanoic acid (OTPBA–SPION) through the surface carboxylate groups. The nanocomposite (CMDP–OTPBA–SPION) was characterized by TEM, XPS, EDX, SQUID, ICP-AES, and zeta potential. A relatively high Pt loading capacity (ca. 13%) is achieved with this drug delivery system. The DNA binding ability of CMDP–OTPBA–SPION is prominent in acidic medium (pH 5.2) but is insignificant under normal physiological conditions (pH 7.4), suggesting that an acidic cancerous environment is favourable for the release of the platinum pharmacophore from the composite. The transverse relaxivity of CMDP–OTPBA–SPION in phosphate-buffered saline is 141.9 mM−1 s−1 in terms of Fe concentration, implying that the composite could be used as a negative-contrast agent for MRI. The cytotoxicity of the composite toward MCF-7 and HeLa cancer cells displays slow and time-dependent characteristics, reaching a level comparable to that of cisplatin at 72 h. The diagnostic capability and tumor-specific accumulation of the composite are verified in vitro and in vivo by the time-dependent negative-contrast enhancement effect in MRI using MCF-7 cells and tumor-bearing mice, respectively. The results demonstrate that CMDP–OTPBA–SPION can potentially be used as an anticancer theranostic agent for simultaneous targeted therapy and MRI under an external magnetic field.
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![Ferrate(4-),[L-valyl-L-glutaminyl-L-lysyl-L-cysteinyl-L-alanyl-L-glutaminyl-L-cysteinyl-L-histidyl-kN-L-threonyl-L-valyl-L-glutamicacid cyclic (4®12'),(7®7')-bis(thioether) with7,12-bis(1-mercaptoethyl)-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-dipropanoato(6-)-kN21,kN22,kN23,kN24]-,hydrogen (1:4)](http://img.cochemist.com/ccimg/31000/30975-71-4_b.png)
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