王晓勇
生物无机化学和无机药物化学。
个性化签名
- 姓名:王晓勇
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学科领域:
无机化学
- 研究兴趣:生物无机化学和无机药物化学。
王晓勇,男,1986年本科毕业于西北师范大学化学系,获理学学士学位;1994年硕士毕业于山东大学,获医学硕士学位;2003年博士毕业于南京大学,获理学博士学位。2003至2005年在南京大学配位化学国家重点实验室做博士后研究,现为南京大学医药生物技术国家重点实验室副教授。
主要从事生物无机化学和无机药物化学研究。在生物无机化学方面主要研究金属配合物的生物效应、金属离子与生物大分子(如蛋白质、DNA等)的相互作用以及无机探针分子对核酸和蛋白质的识别。在无机药物化学方面主要研究金属药物的设计合成和作用机理,尤以金属抗癌药物为研究重点。
生物无机化学由无机化学、生物化学、药物学等多个学科交叉而成,其研究成果为干预调控生理过程和预防治疗疾病提供重要依据。无机药物化学综合运用无机化学、有机化学和药物化学研究手段,设计合成含有金属元素的活性化合物,借助金属元素独特的理化性质和生物效应实现诊断治疗疾病的目的。金属抗癌药物和金属造影剂已经在临床中得到广泛应用,其它无机药物也在多种疾病防治中发挥了关键作用。
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成果阅读
409
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成果数
8
【期刊论文】Specific recognition of DNA depurination by a luminescent terbium(III) complex
王晓勇, Xiaohui Wang, Xiaoyong Wang, * Shanshan Cui, Yan Wang, Guangju Chen and Zijian Guo*
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-1年11月30日
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.
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王晓勇, Jinzhuan Wang, Xiaoyong Wang, * Yajie Song, Jing Wang, Changli Zhang, Cunjie Chang, Jun Yan, Lin Qiu, Mingmin Wu and Zijian Guo*
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-1年11月30日
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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【期刊论文】Targeting and delivery of platinum-based anticancer drugs
王晓勇, Xiaoyong Wang* and Zijian Guo*
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-1年11月30日
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.
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【期刊论文】Characterization and cellular uptake of platinum anticancer drugs encapsulated in apoferritin
王晓勇, Ruimin Xing a, Xiaoyong Wang b, *, Changli Zhang a, c, Yangmiao Zhang a, Qi Wang a, Zhen Yang a, Zijian Guo a
Journal of Inorganic Biochemistry 103 (2009) 1039-1044,-0001,():
-1年11月30日
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
Platinum drugs, Anticancer, Apoferritin, Drug delivery, Encapsulation
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王晓勇, Xindian Dong, † Xiaoyong Wang, *, ‡ Miaoxin Lin, † Hui Sun, † Xiaoliang Yang, † and Zijian Guo*, †
Inorg. Chem. 2010, 49, 2541-2549,-0001,():
-1年11月30日
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.
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【期刊论文】The Role of Sulfur in Platinum Anticancer Chemotherapy
王晓勇
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-1年11月30日
Sulfur manifests its influence on platinum anticancer chemotherapy in two aspects: endogenous sulfurcontaining molecules such as cysteine, methionine, glutathione, metallothionein and albumin affect the metabolism of platinum drugs and exert adverse effects on the therapeutic efficacy; exogenous congeners such as amifostine (WR-2721) and dimesna (BNP7787) mitigate the toxic side effects of platinum drugs and serve as chemoprotectants. The platinum-sulfur interactions are ubiquitous in the human body and many occurrences encountered during platinum chemotherapy such as uptake, excretion, resistance, and toxicity are related to them. Thus, sulfur-containing molecules play significant roles in the anticancer mechanism of platinum drugs. In this review, the platinum-sulfur interactions are summarized in detail, which may be important for efficient clinical use of the existing platinum agents and beneficial to the rational design of new generation of platinum-based anticancer drugs.
Anticancer drug, Platinum complex, Sulfur, Platinum-sulfur interaction, Chemotherapy, Chemoprotectant, Resistance
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【期刊论文】Towards the rational design of platinum(II) and gold(III) complexes as antitumour agents
王晓勇
,-0001,():
-1年11月30日
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