Antitumor effect of hydroxy camptothecin-loaded amphiphilic block copolymer nanoparticles

目的研究羟基喜树碱双嵌段共聚物纳米粒（MePEG．PLGA．HCPT．NPs）的抗肿瘤作用。方法选择人肝癌细胞株Bel-7402为体外模型，采用MTT法观察体外肝癌细胞的生长和增殖抑制情况，评价MePEG-PLGA-HCPT-NPs对肝癌细胞的毒性作用；采用激光共聚焦荧光显微镜技术观察其对肝癌细胞摄取药物的影响；采用小鼠H22肝癌细胞实体瘤模型进行体内抑瘤实验观察荷瘤动物的生长情况，测定肿瘤生长抑制率。结果MePEG—PLGA-HCPT．NPs能抑制肝癌细胞的生长增殖，且随羟基喜树碱浓度的升高而增强；激光共聚焦荧光照片显示载药纳米粒能有效地被Bel．7402细胞摄取；MePEG-PLGA-HCPT-NPs对小鼠的H22实体瘤生长具有明显的抑制作用，低、中、高剂量组的生长抑瘤率分别为37．62％、50．31％和70．25％，与对照组相比差异均有统计学意义（P〈0．05）。结论MePEG-PLGA-HCPT-NPs具有较强的体外、体内抗肿瘤作用。与羟基喜树碱注射剂相比，MePEG-PLGA-HCPT-NPs的抑瘤率更高，且与剂量有关，并对肿瘤生长的抑制更为持久。AIM To study the antitumor effect of hydroxy camptothecin（HCPT）-loaded amphiphilic block copolymer nanoparticles（MePEG-PLGA-HCPT-NPs）. METHODS The human hepatoma cell lines Bel-7402 in vitro were selected as model, the cell growth and viability inhibited by MePEG-PLGA-HCPT-NPs were observed and the antitumor cytotoxicity was evaluated by MTT assay. Cellular uptake of HCPT was observed by Confocal fluores- cence microscopy（CLSM）. Hepatocellular carcinoma cell H22 was subcutaneously injected into mice and MePEG- PLGA-HCPT-NPs was administered to the tumor-bearing mice. The growth of tumor was measured, and the inhibi- tory rate of tumor growth was calculated. RESULTS Hepatoma cell growth and viability were inhibited by Me- PEG-PLGA-HCPT-NPs, the inhibition was enhanced with increasing concentrations. CLSM photos indicated that MePEG-PLGA-HCPT nanoparticles enhanced the intracellular uptake of HCPT in Bel-7402 ceils. Marked inhibitory effect of MePEG-PLGA-HCPT-NPs on the transplanted hepatocellular carcinoma H22 was observed in the tumor- bearing mice. The inhibitory rates were 37.62% , 50.31% and 70.25% in the groups treated with low, medium and high dosage of MePEG-PLGA-HCPT-NPs, respectively （P 〈 0. 05 vs control group）. CONCLUSION Me- PEG-PLGA-HCPT-NPs has marked inhibitory effects on tumor growth in vitro and in vivo. The inhibitory effect of MePEG-PLGA-HCPT-NPs is obvious and dose-dependent and higher than that of HCPT injection.福建省医学创新课题项目（编号2014-CXB-35）;厦门市科技计划指导性项目（编号3502220159001

异三核过渡金属配合物〔Fe2Ⅲ MⅡO（OOCC2H5）6L3〕（M=Co,Ni,Mn;L=C5 H5N,H2O）溶液行为的NMR和UV谱表征

A series of new heterotrinuclear transition-metal complexes [(Fe2MO)-M-I-O-I(OOCC2H5)(6)L-3] (M = Co, Ni, Mn; L = C5H5N, H2O) were synthesized and characterized. Their structures and dynamics in different solutions and temperatures were investigated by NMR and UV. Assignments of the H-1 NMR spectra were made on the basis of relative intensities, broadening, substitution with appropriate ligands and spin-lattice relaxation. Experimental results shows that there is antiferromagnetic exchange interaction among the three metal ions within M3O core. It is found that these complexes in DMSO, CD3CN, CDl(3) and CD3COCD3 solvents are stable at room temperature and their structures in solution are the same as their crystal ones. However, the complexes decomposed into carboxylic acid, pyridin and metal ions in water. The results may be helpful in guiding synthesis of similar complexes

Antitumor effect of mitomycin C chitosan nanoparticles on H_(22) tumor-bearing mice

目的研究丝裂霉素C壳聚糖纳米粒(MMC-CS-nPS)对H_(22)荷瘤小鼠的肿瘤抑制作用。方法采用小鼠H_(22)肝癌细胞实体瘤模型进行体内抑瘤实验,观察荷瘤动物的生长情况,并测定肿瘤生长抑制率;肿瘤组织病理学切片行HE染色以进行形态学观察。结果 MMC-CS-nPS对小鼠的H_(22)实体瘤生长具有明显的抑制作用,低、中、高剂量组的抑瘤率分别为52.23%、66.93%、80.91%,与对照组相比有统计学意义(P<0.05)。病理组织学观察显示,各剂量组对肿瘤组织都有不同程度的破坏,肿瘤细胞大量变性坏死。结论 MMC-CS-nPS具有较强的体内抗肿瘤作用,与丝裂霉素针剂相比其抑瘤率更高,且与剂量有关,并对肿瘤生长的抑制更为持久。AIM To investigate the antitumor effect on H_(22) tumor-bearing mice treated with mitomycin C chitosan nanoparticles(MMC-CS-NPs).METHODS Hepatocellular carcinoma cell H_(22) was subcutaneously injected into mice and MMC-CS-NPs were administered to the tumor-bearing mice.The growth of tumor-bearing mice was observed,and the inhibition rate of tumor growth was calculated.The tumor tissue samples were taken and examined to assess the inhibitory effects of MMC-CS-NPs on tumor growth in the mice.RESULTS Marked inhibitory effect of MMC-CS-NPs on the transplanted hepatocellular carcinoma H_(22) was observed in the tumor-bearing mice.The inhibition rates were 52.23%,66.93%and 80.91%in the groups treated with low,medium and high dosage of MMC-CS-NPs,respectively(P < 0.05vs control group).Histopathological examination revealed widespread necrosis with massive accumulation of infiltrating lymphocytes and plasmacytes in the tumors.CONCLUSION MMC-CS-NPs has marked inhibitory effects on tumor growth in vivo.The inhibitory effects of MMC-CS-NPs are obvious and dose-dependent and higher than those of mitomycin injection.厦门市科学技术计划项目资助(编号3502Z20114007

Study on the bioeffect of hydroxycamptothecin loaded PLA microbubbles on hepatocellular carcinoma cell enhanced by ultrasonic irradiation

目的:探讨载羟基喜树碱聚乳酸微泡超声辐照下对肝癌细胞的生物学效应。方法:选择人肝癌细胞株bEl-7402为体外模型,采用MTT比色分析法,观察羟基喜树碱聚乳酸微泡对肝癌细胞的生长和增殖抑制情况,评价载药微泡对肝癌细胞的毒性作用;采用激光共聚焦荧光显微镜技术和流式细胞仪技术观察超声辐照下载药微泡对肝癌细胞摄取药物的影响。结果:羟基喜树碱聚乳酸微泡抑制肝癌细胞的生长增殖,且随羟基喜树碱浓度的升高而增强;激光共聚焦荧光照片显示:与未超声的肝癌细胞相比,超声辐照下,肝癌细胞内羟基喜树碱的绿色荧光增强,说明细胞摄取羟基喜树碱的量增加;流式细胞仪数值:细胞内羟基喜树碱荧光值对照组仅37.5,未超声实验组为71.9;超声实验组为91.3。结论:羟基喜树碱聚乳酸微泡对肝癌细胞bEl-7402有毒性作用,且超声辐照对细胞摄取药物有促进作用。其超声辐照下对肿瘤细胞生物学效应的评价可将为其今后的临床超声治疗提供必要依据。OBJECTIVE To investigate the bioeffect of hydroxycamptothecin(HCPT) loaded PLA microbubbles on hepatocellular carcinoma cells enhanced by ultrasonic irradiation.METHODS The human hepatoma cell lines Bel-7402 in vitro were selected;the cell growth and viability inhibited by HCPT-loaded microbubbles were observed and the anti-tumor cytotoxicity was evaluated by MTT assay.Cellular uptake of HCPT when treated with drug-loaded microbubbles in combination with ultrasound was observed by confocal fluorescence microscopy(CLSM) and flow cytometry(FCM)).RESULTS Hepatoma cell growth and viability were inhibited by HCPT-loaded microbubbles,the inhibition was enhanced with increasing the concentrations.CLSM photos indicated: compared to the hepatoma cells with no exposed to ultrasound,the green fluorescence of HCPT in hepatoma cells increased by ultrasound;FCM data indicated: the fluorescent data of control group was 37.5,the fluorescent data of experimental group with no exposed to ultrasound was 71.9,and the fluorescent data of experimental group with exposed to ultrasound was 91.3.CONCLUSION HCPT-loaded microbubbles had toxic effects on hepatoma cell lines Bel-7402.It was indicated that an increased cellular uptake of HCPT treated with drug-loaded microbubbles exposed to ultrasound.The evaluation of the bioeffect of hydroxycamptothecin(HCPT) loaded PLA microbubbles on hepatocellular carcinoma cells enhanced by ultrasound will provide useful information for future clinical application.福建省卫生厅青年科研项目(编号:2009-2-79

Ag生长温度对Ag/ZnO肖特基接触特性的影响

利用脉冲激光沉积(PLD)方法在Si衬底上制备了ZnO单晶体薄膜,并在不同温度下生长了Ag膜作为肖特基电极,研究了Ag与ZnO的接触特性.利用X射线衍射仪、扫描电子显微镜和Ⅰ-Ⅴ测试方法对样品的晶体质量、结构和电学性质进行了分析.结果表明,ZnO薄膜具有高度的c轴择优取向,Ag膜随生长温度的不同的晶体质量有较大差异.样品在室温下的Ⅰ-Ⅴ测试结果表明Ag电极的生长温度对Ag/ZnO接触性能有重要影响.在150℃和200℃生长的Ag电极实现了Ag与ZnO的肖特基接触,电极生长温度低于150℃和高于200℃的样品Ag与ZnO均为欧姆接触.经过分析,肖特基接触的形成依赖于在Ag与ZnO接触界面处形成的p型反型层

NMR and UV Spectroscopic Characterization on the Solution Behavior of Heterotrinuclear Transition metal Complexes 〔Fe_2~ⅢM~ⅡO(OOC_2H_5)_6L_3〕 (M = Co, Ni, Mn; L = C_5H_5N, H_2O)

在合成和表征了一系列新的异核异价三核过渡金属羧酸配合物〔Fe2 Ⅲ MⅡ O (OOCC2 H5 ) 6 L3〕 (M =Co ,Ni,Mn ;L =C5 H5 N ,H2 O)的基础上 ,利用多种NMR技术并结合UV谱研究了这些配合物在不同溶剂介质和温度下的谱学特征和动力学性质。利用谱峰积分比例、线宽、相同骨架分子的配体取代和纵向弛豫时间对1 HNMR谱进行了归属。实验结果表明 :这类配合物的金属离子间通过中心氧桥存在一定的反铁磁相互作用 ,从而在整体上削弱了顺磁性的影响 ,仍能观察到NMR谱。实验还发现这些配合物在CD3CN和DMSO溶剂中的结构与晶体结构一致 ,而在水中则分解为金属离子、羧酸盐和吡啶。这些结果有助于指导类似配合物的合成A series of new heterotrinuclear transition metal complexes 〔Fe 2 ⅢM ⅡO(OOCC 2H 5) 6L 3〕 (M = Co, Ni, Mn; L = C 5H 5N, H 2O) were synthesized and characterized. Their structures and dynamics in different solutions and temperatures were investigated by NMR and UV. Assignments of the 1H NMR spectra were made on the basis of relative intensities, broadening, substitution with appropriate ligands and spin lattice relaxation. Experimental results shows that there is antiferromagnetic exchange interaction among the three metal ions within M 3O core. It is found that these complexes in DMSO, CD 3CN, CDCl 3 and CD 3COCD 3 solvents are stable at room temperature and their structures in solution are the same as their crystal ones. However, the complexes decomposed into carboxylic acid, pyridin and metal ions in water. The results may be helpful in guiding synthesis of similar complexes.国家自然科学基金! (批准号 :1960 50 0 4 ,2 9832 0 2 0 ) ;; 结构化学国家重点实验室;; 固体表面物理化学国家重点实验室基金资助项

JUNO Sensitivity on Proton Decay p→νˉK+p\to \bar\nu K^+ Searches

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this paper, the potential on searching for proton decay in $p\to \bar\nu K^+$ mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits to suppress the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar\nu K^+$ is 36.9% with a background level of 0.2 events after 10 years of data taking. The estimated sensitivity based on 200 kton-years exposure is $9.6 \times 10^{33}$ years, competitive with the current best limits on the proton lifetime in this channel

JUNO sensitivity on proton decay p → ν K + searches*

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this study, the potential of searching for proton decay in the $p\to \bar{\nu} K^+$ mode with JUNO is investigated. The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar{\nu} K^+$ is 36.9% ± 4.9% with a background level of $0.2\pm 0.05({\rm syst})\pm$$0.2({\rm stat})$ events after 10 years of data collection. The estimated sensitivity based on 200 kton-years of exposure is $9.6 \times 10^{33}$ years, which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies