Research Progress on Nanomedicine Carriers Targeting Tumor HypoxiaZHANG Li-li, LIU Qi, SUN Guo-hui, ZHAO Li-jiao*,ZHONGRu-gang(Beijing Key Laboratory of Environmental & Viral Oncology, College of Life Science&Bioengineering, Beijing University of Technology, Beijing 100124, China), HuaxueShiji, 2019, 41(10), ～
Abstract:Hypoxia-targetingnanocarrier has become a hot research topic, because it can targetedly release drug to the hypoxic area of tumorso that the chemotherapy exerts anti-tumor effect with highefficacy and low toxicity. Azobenzene, nitroimidazole and nitrobenzene compounds have good hypoxic reduction properties and normoxic stability. So, they are widely used as hypoxic responsive groups to achieve hypoxia-targeting action on tumors.The hypoxia-targetingnanocarrier can encapsulate chemotherapies, fluorescent indicators or photosensitizers, and deliver them to the hypoxic region of tumor.Then the nanocarrierwas fragmented by the reduction of the hypoxia-responsive group followed by the release of drug exerting anti-tumor activity. In addition,some hypoxia-responsive groups act asradiosensitizers and can be used in combination ofradiotherapy with chemotherapy within the same nanocarrier.The hypoxia-targetingnanomedicinecarriers developed in recent years for chemotherapeutics deliverywas reviewed, as well as for radiotherapy, photodynamic therapy and tumor imaging, which will providereferences for the development of novel targeted anticancer drugs.
Keywords:nanocarrier; hypoxia-targeting action; anticancer drug; chemotherapy; radiotherapy
庄琢琛1，贾帅楠1，李劲涛1，崔鑫1，孙国辉1，Pramod Upadhyaya 2，赵丽娇*1，钟儒刚1
（1.北京工业大学 生命科学与生物工程学院 环境与病毒学北京市要点试验室，北京 100124；
2. 明尼苏达大学Masonic癌症中心，美国明尼苏达州 明尼阿波利斯市 55455）
摘要：苯并[a]芘(B[a]P)和人乳头瘤病毒(HPV)均是导致人类癌症的重要要素，前者是环境中广泛存在的致癌物，后者可诱导皮肤和黏膜鳞状上皮细胞反常增殖从而诱发癌症。流行病学根据标明烟草烟气与HPV协同效果可促进口咽鳞癌、头颈部鳞状细胞癌和肺癌等恶性肿瘤的发作，可是关于HPV与多环芳烃（PAHs）的协同致癌效果机制尚不清晰。经过平板克隆构成试验、细胞划痕试验以及细胞侵袭试验对B[a]P和HPV的协同致癌效果进行了研讨，比较了经B[a]P处理后人宫颈癌HeLa细胞(HPV阳性)和C33A细胞(HPV阴性)表型的改动；用高效液相色谱-电喷雾串联质谱法(HPLC-ESI-MS/MS)法对B[a]P导致的首要DNA加合物——二氢二醇环氧化物-N2-脱氧鸟苷(BPDE-N2-dG)进行了定量剖析。成果标明，浓度为10 ～ 40 μmol/L的B[a]P能够明显促进HeLa和C33A细胞的侵袭和克隆构成才能，且呈剂量效应联系；经B[a]P处理后HeLa细胞的侵袭和克隆构成才能均明显高于C33A细胞(p<0.01)，并明显高于对照组HeLa细胞(p<0.01)。经浓度为10 μmol/L的B[a]P处理后HeLa细胞及C33A细胞中BPDE-N2-dG水均匀最高，别离为（4172±124）fmol/mg DNA和 （1255±228）fmol/mg DNA；且各B[a]P处理浓度下的HeLa细胞中BPDE-N2-dG的水均匀明显高于C33A细胞(p<0.01)，证明了HPV能明显促进B[a]P对DNA的损害效果，为进一步提醒B[a]P和HPV的协同致癌效果供给了根据。不只为B[a]P和HPV相关癌症的防治供给了新战略，并且将为癌症病因学研讨供给新的办法。
中图分类号：R914.2 文献标识码：A 文章编号：0258-3283（2019）--
Synergistic Effect on DNA Damage Induced by HPV and Polycyclic Aromatic Hydrocarbons ZHUANG Zhuo-chen1, JIA Shuai-nan1, LI Jin-tao1, CUI Xin1, SUN Guo-hui1, UPADHYAYA Pramod2, ZHAO Li-jiao*1, ZHONG Ru-gang1 (1. Beijing Key Laboratory of Environmental and Viral Oncololgy, College of Life Science and Bio-Engineering, Beijing University of Technology, Beijing 100124, China; 2. Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, United States)
Abstract: Both benzo[a]pyrene (B[a]P) and human papillomavirus (HPV) are important factors inducing human cancer. The former is a carcinogen widely found in the environment, and the latter can induce cancer by resulting in abnormal proliferation of cutaneous and mucosal squamous cells. Epidemiological evidence suggests that tobacco smoke and HPV can synergistically promote the development of malignant tumors such as oropharyngeal squamous cell carcinoma, head and neck squamous cell carcinoma and lung cancer. However, the mechanism of the synergistic carcinogenesis of HPV and PAHs is unclear. Cell colony formation assay, cell scratch assay and cell invasion assay were conducted to assess the synergistic carcinogenesis of HPV and B[a]P, and the cell phenotypic changes of the human cervical carcinoma HeLa cells (HPV positive) and C33A cells (HPV negative) exposed to B[a]P. High performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-ESI-MS/MS) was used to quantitatively determine the main DNA adduct caused by B[a]P, dihydroglycol epoxide-N2-deoxyguanosine (BPDE-N2-dG). The results showed that the ability of cells invasion and colony formation of HeLa and C33A were significantly promoted by 10-40 μM B[a]P with a dose-response relationship. The invasion and colony formation of B[a]P-treated HeLa cells were significantly higher than those of C33A cells (p<0.01) and those of HeLa cells without B[a]P treatment (p<0.01). The group treated with 10 µM B[a]P in HeLa cell and C33A cell induced the highest levels of BPDE-N2-dG, 4172±124 fmol/mg DNA and 1255±228 fmol/mg DNA, respectively. The levels of BPDE-N2-dG in HeLa cells treated with B[a]P were significantly higher than those in C33A cells (p<0.01). These combined results suggest that HPV could effectively promote DNA damage induced by B[a]P, which provide a reasonable explanation for the results of cellular experiments described above. It provides not only a new strategy for the prevention and treatment of B[a]P and HPV-related cancer, but also a new method for cancer etiology research.
（北京工业大学 生命科学与生物工程学院学院 环境与病毒学北京市要点试验室，北京 100124）
中图分类号：R914.5 文献标识码：A 文章编号：0258-3283（2019）--
Synthesis and Reduction Activity Evalution of Hypoxia-activated Azobenzene AGT Inhibitors YU Ran, ZHANG Li-li, SUN Guo-hui, CUI Xin, REN Ting, ZHAO Li-jiao*, ZHONG Ru-gang (Beijing Key Laboratory of Environmental and Viral Oncology, College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China), Huaxue Shiji, 2019, 41( ), ～
Abstract：O6-Alkylguanine-DNA alkyltransferase (AGT) is an important DNA repair enzyme. AGT can lead to drug resistance of chemotherapy by repairing DNA damages of tumor cells, while it also protects normal cell DNA from the damages induced by alkylating agents. Design and synthesize a series of AGT inhibitors with tumor hypoxia targeting that can be specifically reduced in tumor hypoxic environments, releasing the AGT inhibitor, O6-3-aminobenzylguanine (ABG). The compounds cannot be activated and exert AGT-inhibiting activity under normoxic conditions. Therefore, the compounds can be used in combination with alkylating agents, such as chloroethylnitrosourea, to increase the sensitivity of the tumor cells to chemotherapy by targetingly inhibiting the AGT activity in tumor hypoxia areas. Four O6-alkylguanine derivatives with azotoluene moiety as hypoxia-activating groups were designed and synthesized. After in vitro experiments to simulate the hypoxic environment in solid tumor, it was confirmed that the four compounds can be selectively reduced to AGT inhibitor (ABG) under the hypoxic conditions, and the reducing activity of the four target compounds was (E)-6-((3-((4-(dipropylamino)phenyl)diazenyl)benzyl)oxy)-9H-purin-2-amine > (E)-6-((3-((4-(ethylamino)phenyl) diazenyl)benzyl)oxy)-9H-purin-2-amine > (E)-6-((3-((4-(diethylamino)phenyl)diazenyl)benzyl)oxy)-9H-purin-2 -amine > (E)-6-((3-((4-(methylamino)phenyl)diazenyl)benzyl)oxy)-9H-purin-2-amine. It provided new ideas for the development of novel tumor targeting chemotherapy and for the design of anti-tumor combination strategies with high-efficacy and low-toxicity.
Key words：O6-alkylguanine-DNA-alkyltransferase; hypoxia-activation; AGT inhibitor; tumor-targeting; azo group
(北京工业大学 化学化工系 绿色催化与别离北京市要点试验室，北京 100124)
摘要：用细密的纳米二氧化硅球（DNSS）作为载体，经过硅烷试剂（APTES）对其外表进行改性，并引进荧光分子3,4,9,10-苝四羧酸酐（PTD）和聚丙烯酸（PAA）别离得到APTES-DNSS、PTD@DNSS和PAA@DNSS三种有机-无机杂化资料。选用XRD、FT-IR、SEM、TG、PL等剖析手法别离对上述资料的结构特征和织构参数以及热稳定性和荧光功用进行了表征。并以布洛芬（IBU）为模型药物，要点调查了以PAA@DNSS为载体的pH灵敏释药功用和发光行为。成果标明经过APTES改性以及外表嫁接PTD和PAA并不能改动DNSS的球形特征和约250nm的颗粒尺度，可是经过嫁接PTD赋予了样品PTD@DNSS的荧光功用，别离在400 nm和450 nm邻近呈现两个发射峰，进一步负载PAA后样品PAA@DNSS则具有较强的pH灵敏释药功用，特别是在pH 7.4的释药条件下，样品PAA@DNSS不只具有较高的释药率，并且坚持较强的荧光功用。上述成果阐明嫁接在APTES-DNSS外表的PAA和PTD对药物开释功用和发光行为存在着较强的外表效应。
中图分类号：O647.3 文献标识码：A 文章编号：0258-3283（2019）--
Preparation and Characterization of Perylene-126.96.36.199-tetracarboxylic-dianhydride and Polyacrylic Acid Coated Density Nano-Sio2 Microspheres and Application in Controlled Release of Ibuprofen Song Lin-yan, Tang Xiao-wu, Sun Jihong* (Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing 100124, China) Huaxue Shiji, 2019, 41(10), ～
Abstract: Three kinds of organic-inorganic hybrid materials: APTES-DNSS, PTD@DNSS and PAA@DNSS were obtained by using density nano-silica sphere (DNSS) as a carrier via modification by silane reagent (APTES) and subsequent introduce of fluorescence molecule 3,4,9,10-perylene tetracarboxylic anhydride (PTD) and polyacrylic acid (PAA). Their structural features and texture parameters, as well as thermal stability and fluorescence properties were characterized by means of XRD, FT-IR, SEM, TG, and PL methods. Using ibuprofen (IBU) as a model drug and PAA@DNSS as a carrier, their pH-sensitive drug release performances and luminescence behaviors were emphatically investigated. The results showed that the modification of APTES and surface grafting of PTD and PAA could not change the spherical morphology of DNSS and its particle size of around 250 nm, but the fluorescence properties of PTD@DNSS were provided by grafting PTD, exhibiting two emission peaks centered at near 400 nm and 450 nm, respectively. After further loading PAA, PAA@DNSS showed the good pH-responsive behaviors. Especially, PAA@DNSS not only exhibited a higher release amount under the release condition of pH 7.4 than that pH 3.0, but also maintained strong fluorescence properties. These results demonstrated that PAA and PTD grafted on the surface of APTES-DNSS have a strong surface effect on drug release properties and luminescence behaviors.
Key words: nano-silica, ibuprofen; luminescence properties; pH-sensitive release
（贵州民族大学 a. 生态环境工程学院，b. 资料科学与工程学院，贵州 贵阳 550025）
摘要：以六方氮化硼（h-BN）润饰玻碳电极（GCE-BN）为基底，苯酚为功用单体，经过电聚合法成功制备了可用于水样中氯氰菊酯（CYP）快速检测的分子印迹聚合膜传感器。凭借拉曼光谱仪和扫描探针显微镜表征聚合膜的物相组成和外表结构，选用恒电位诱导法洗脱模板分子，差分脉冲伏安法（DPV）点评传感器的灵敏度。成果标明：传感器呼应电流改动值（Δi）与氯氰菊酯的浓度在2.0×10-8 ～ 3.0×10-7 mol/L范围内呈杰出的线性联系，检出限低至8.5×10-9 mol/L，水样加标均匀回收率在96.3% ～ 100.2%之间。该传感器制备简略，检测本钱低价、兼具杰出的稳定性、挑选性，具有杰出运用远景。
中图分类号：O657.1 文献标识码：A 文章编号：0258-3283（2019）
Determination of Cypermethrin by Hexagonal Boron Nitride Modified Molecularly Imprinted Electrochemical Sensor DONG Ze-ganga, b，LAN Tian-yua，MA Li-jiaoa，DU Hai-jun*a，YANG Yangb (a. College of Eco-environmental Engineering, b. School of Materials Science and Engineering, Guizhou Minzu University, Guiyang 550025, China), Huaxue Shiji, 2019, 41(10),
Abstract: The h-BN modified glass carbon electrode (GCE-BN) was used as substrate and phenol was used as the functional monomer. The molecularly imprinted polymer membrane sensor was successfully prepared by electropolymerization, which can rapidly detect cypermethrin(CYP) in water samples. The phase composition and surface morphology of the polymerized membrane were characterized by Raman spectroscopy and scanning probe microscopy. The template molecules were eluted by potentiostatic induction, and the sensitivity of the sensor was evaluated by differential pulse voltammetry (DPV). The results showed that response current (Δi) of sensor had a good linear relationship with the concentration of cypermethrin in the range of 2.0×10-8 ～ 3.0×10-7 mol/L. The detection line was as low as 8.5×10-9 mol/L, and the average recovery of the water sample was between 96.3% ～ 100.2%. This sensor is simple in preparation, low cost in detection, good stability and selectivity, and has a good application prospects.
Key words: h-BN; cypermethrin; phenol; molecularly imprinted sensor
（河西学院 化学与化工学院 甘肃省高校河西走廊特征资源运用省级要点试验室，甘肃 张掖 734000）
摘要：以钼酸钠、氯化钴为质料，选用简略化学沉淀法制备前驱体CoMoO4，然后将CoMoO4和Na2S经过离子交换反响组成双金属硫化物CoMoS4。选用X射线衍射（XRD）、扫描电镜（FESEM）、比外表积测验（BET）表征了产品的组成、结构和描摹，用循环伏安、恒电流充放电等测验办法对电极资料的电化学功用进行了研讨。成果标明，当电流密度为1 A/g时，CoMoS4电极资料的比电容值为456 F/g，是Co-S的2.8倍，Mo-S的1.4倍；且1000次循环后，比电容仍坚持88%，该电极资料显示出杰出的电化学功用。
中图分类号：O646 文献标识码:A 文章编号：0258-3283（2019）
Preparation and Electrochemical Properties of CoMoS4 Electrode Materials JIN Xiao-qing*, XING Jia-bin, REN Rui-xing, QI Ya-e (Key Laboratory of Hexi Corridor Resourses Utilization of Gansu, Department of Chemistry, Hexi University, Zhangye 734000, China), Huaxue Shiji, 2019, 41（10）
Abstract: By using NaMoO4∙2H2O and CoCl2∙6H2O as raw materials, the CoMoO4 precursor was synthesized via a chemical co-precipitation method. Then the CoMoO4 precursor and Na2S was ion-exchanged to form bimetallic sulfide of CoMoS4. In this work, the composition, microstructure and morphology of the samples were systematically characterized by X-ray diffraction (XRD), Field emission scanning electron microscopy (FE-SEM) and Brunner−Emmet−Teller (BET) measurement. The electrochemical performance were investigated by cyclic voltammetry and constant current charge/discharge techniques. The results show that the CoMoO4 electrode material has excellent electrochemical performance. The composites have a superior specific capacitance of 456 F/g at 1A/g, which is 2.8 times of the Co-S nanoparticles and 1.4 times of the Mo-S nanoparticles, and remains about 88% of the initial capacitance after 1000 cycles at current density of 1 A/g, indicating the CoMoS4 composite of excellent electrochemical performance.
Key words: electrode material；CoMoS4；ion exchange；capacitance performance
(山东理工大学 化学化工学院，山东 淄博 255049)
摘要：选用热聚合法，以三聚氰胺为前驱体组成类石墨相氮化碳（g-C3N4）光催化剂。并用相同的办法别离以掺入0.5 wt% MgCl2、CaCl2、BaCl2的三聚氰胺为前驱体组成M/ g-C3N4（M ＝ Mg、Ca、Ba）复合光催化剂。运用X射线衍射（XRD）、傅里叶变换红外光谱（FT-IR）、紫外可见漫反射（UV-Vis DRS）、扫描电子显微镜（SEM）等对所制备的光催化剂进行表征。在可见光照射下，经过光催化降解亚甲基蓝（MB）溶液研讨碱土金属的掺杂对g-C3N4光催化活性的影响。研讨标明，Mg、Ca、Ba等碱土金属的掺杂对g-C3N4的光催化活性别离提升了5.09、3.66、2.19倍。
中图分类号： O643 文献标识码：A 文章编号：0258-3283（2019）--
Visible-light Photocatalysis of Alkaline-earth Metals-doped Graphitic Carbon Nitride AI Bing*, LI Si-yuan, LIU Fan, HAN Yong-lei, LI De-gang (School of Chemistry and Chemical Engineering, Shandong University of Technology, Shandong 255049, China), Huaxue Shiji, 2019, 41（10）
Abstract: The graphitic carbon nitride (g-C3N4) photocatalyst was prepared in this work by used thermal polymerization method. Moreover, the M/g-C3N4 (M =Mg, Ca, Ba) composite photocatalyst was prepared by adding 0.5 wt% of MgCl2, CaCl2, BaCl2. The samples were characterized by X-ray diffraction (XRD), fourier transform infrared spectroscopy (FT-IR), UV-visible diffuse reflectance spectroscopy (UV-Vis DRS) and scanning electron microscopy (SEM). The effect of alkaline-earth metals-doped g-C3N4 on the photocatalytic activity was investigated by degradation of methylene blue under the visible light irradiation. The M/g-C3N4 showed the photoactivity of MB evolution 5.09 times, 3.66 times and 2.19 times higher than g-C3N4 under the 0.5 wt% doped of Mg, Ca, Ba respectively.
Key words: thermal polymerization; g-C3N4; alkaline-earth metals; photocatalysis
（延边大学医学院 a.药理教研室，b.药学院，吉林 延吉 132002）
摘要: 以天然产品芦荟大黄素为先导化合物，规划、组成了6个未见报导的芦荟大黄素唑类衍生物，结构经核磁共振氢谱、碳谱和质谱确证。以5-氟尿嘧啶（5-Fu）为阳性对照药，选用MTT比色法进行化合物按捺人体结肠癌细胞HCT116的体外活性测验。成果标明，大部分方针化合物对结肠癌细胞的按捺活性强于先导化合物芦荟大黄素，其间3-(((1H-1,2,4-三唑-3-基)硫基)甲基)-1,8-二羟基蒽-9,10-二酮、3-(((5-氨基-4H-1,2,4-三唑-3-基)硫基)甲基)-1,8-二羟基蒽-9,10-二酮对HCT116细胞的对折按捺浓度(IC50)别离为15.18、14.15 μmol/L，明显强于阳性对照药5-Fu (IC50为24.80 μmol/L)。
中图分类号：R914.5 文献标识码：A 文章编号： 0258-3283（2019）
Synthesis and Antitumor Activity of Aloeemodin-azole Derivatives CAO Li-hua a, SHEN Qing-kunb,QUAN Zhe-shan *b (1. Clinical Department of Pharmacy, The 95 Hospital of PLA, Putian Fujian 351100, China; 2. Department of Pharmacology, Yanbian University College of Medicine, Yanji 133002, China; 3. College of Pharmacy, Yanbian University, Yanji 133002, China
Abstract: Six unidentified aloe-emodin azole derivatives were designed and synthesized with the natural product aloe-emodin as the lead compound. Their structures were confirmed by 1H- NMR, 13C- NMR spectra,and MS. The in vitro antiproliferative activity of the compounds in the HCT116 cancer cell lines was evaluated via MTT assay and the 5-Fu as a positive control drug. The results showed that most of the target compounds inhibited colon cancer cells more stronger than the lead compound aloe-emodin. The half-inhibitory concentrations (IC50) of compounds 1a and 1c on HCT116 cells were 15.18 and 14.15 μM, respectively, which were significantly stronger than the positive control drug 5-Fu (IC50 is 24.80 μM).
Keywords: aloe emodin; azole; synthesis; antitumor activity
(1.徐州医科大学 药学院，江苏 徐州 221000；2. 江苏省新药研讨与临床药学要点试验室，江苏 徐州 221000)
中图分类号：O626.2, R914.5 文献标识码：A 文章编号：0258-3283（2019）--
Synthesis of Benzimidazoles with O-phenylenediamine as Substrate MOU Jie* 1, 2 , MENG Si-han 1, ZHAO Yu 2, ZHANG Peng-peng 2, LIU Jie 2(1 School of Pharmacy, Xuzhou Medical University, Xuzhou 221000, China 2 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou 221000, China), Huaxue Shiji, 2019, 41(10), ～
nzimidazole is an important pharmacophore and privileged structure which has been widely utilized in pharmaceuticals and medicinal chemistry. Due to its extensive applications, the efficient synthetic approaches of benzimidazole derivatives have attracted much attention and make great progress in recent years. This review summarizes the latest information available on the synthesis of benzimidazole derivatives from o-phenylenediamine as substrate which include the conventional as well as green synthetic approach. The synthesis of benzimidazoles from o-phenylenediamine with aldehyde or nitrile showed higher activity than the other carbonyl compounds such as acid or esters. The chemoselectivity of the terminal product depends on the catalyst system. The combination of green chemistry and photocatalysis is helpful to develop more effective synthesis methods of benzimidazole derivatives. The progresses in synthetic methodologies of benzimidazole have been reviewed which can promote its application in drug development.
Key words: benzimidazole; o- phenylenediamine; synthesis
（云南中烟工业有限责任公司技能中心 云南省烟草化学要点试验室，云南 昆明 650231）