荧光偏振光谱法探测光动力过程中癌细胞膜的流动性

以DPH作荧光探剂,用荧光偏振光谱法研究了金属酞菁配合物苯硫基钛菁锌(C₅₆H₃₂N₈S₄Zn)在光动力过程中,不同光照时间对乳腺癌细胞膜流动性的影响。实验结果表明,经光照激发光敏剂金属酞菁后,荧光标记团的偏振度增大,癌细胞膜流动性降低,微黏度升高。说明这是光动力治疗的疗效所在。用酶联免疫检测(MTT法)不同光照时间对细胞存活的影响,结果显示癌细胞最低存活率与膜流动性降低成正相关。这表明光动力过程在一个相近的程度影响癌细胞膜的流动性和增殖,提示光动力过程可能通过影响细胞膜流动性引起细胞增殖变化,即细胞膜是光动力作用的一个位点。     

轴向嘧啶衍生物修饰硅酞菁的光谱性质、光动力抗癌活性及与白蛋白相互作用的研究

研究了一种新型轴向修饰硅酞菁,即二(2-氨基-6-三氟甲基-4-嘧啶氧基)硅酞菁(SiPcF)的光物理光化学性质、离体光动力抗癌活性以及与白蛋白的相互作用。结果表明,SiPcF的Q带最大吸收峰波长686 nm,摩尔吸光系数为2.3×105 mol-1·L ·cm-1,荧光发射峰694 nm,荧光量子产率为0.46,光敏化产生单线态氧的量子产率为0.38,是有效的1O₂光敏剂。SiPcF与牛血清白蛋白(BSA)具有较强的相互作用,两者的结合常数为4.33×105mol·L-1,结合位点数为1。离体细胞实验表明,SiPcF具有较高的光动力抗癌活性,对人肝癌细胞HepG2的IC₅₀值为5×10-7mol·L-1。     

一种轴向核苷修饰硅酞菁的合成与光动力抗癌活性

合成了一种轴向核苷修饰硅酞菁,即二[5′-(2′,3′-O-异丙基)-5-甲基胞苷氧基] 硅酞菁,并通过1H NMR和HR-MS等手段进行了表征。该化合物在N,N-二甲基甲酰胺和含1% Cremophor EL水溶液中以单体形式存在,Q带最大吸收波长分别位于676和679 nm,荧光发射峰分别位于685和689 nm。离体光动力抗癌活性表明,该化合物具有显著的光动力抗癌活性,对人肝癌细胞HepG2的半致死浓度(IC₅₀)低至7.8×10-8mol·L-1。荧光共聚焦显微镜研究显示,SiPcG可定位于细胞线粒体中。研究表明,SiPcG是一种有发展潜力的新型抗癌光敏剂。     

Au@TiO_2纳米核壳与HMME结合体的制备及其光动力疗效初探

光动力疗法(PDT)是一种高效、安全、微创的新型治疗方法,国产光敏剂血卟啉单甲醚(HMME)介导的光动力疗法由于其成分单一、单态氧产量高及光敏周期短,临床上已用于脑胶质瘤和鲜红斑痣的治疗。为了进一步提高光动力疗效,本研究基于晶种生长法制备稳定粒径均一的吸收峰在530nm的阳离子金纳米球。采用毒性低且阴离子电解活化作用强的聚(四-苯乙烯磺酸钠)(PSS)进行修饰。利用静电吸引力将钛源TiCl_3水解的TiOH~(2+)与其结合并氧化制备AuNP@TiO_2核壳,通过改变NaHCO_3量制得不同TiO_2壳层厚度的AuNP@TiO_2核壳,并进一步将其与HMME结合制备结合体。采用紫外-可见吸收光谱、红外光谱、激光纳米粒度仪和透射电镜对所制样品进行表征。结果表明新型的光敏剂粒径均匀,结构稳定。最后采用细胞实验验证了其光动力疗效。总之,该研究合成了新型的Au@TiO_2-HMME纳米光敏剂,通过人口腔表皮样癌细胞系KB细胞与新型核壳纳米结构的光动力作用,与纯HMME相比,在最优条件下可提高约35%的细胞杀伤率。     

光动力作用可致人肝癌细胞HepG2凋亡的实验研究

为探讨光动力作用（PDT）对体外培养的人肝癌细胞HepG2的杀伤效应，应用体外培养的人肝癌细胞HepG2，采用血卟啉衍生物（HPD）为光敏剂，用He-Ne激光器（波长632．8nm，能量密度120J／cm^2）进行激光照射，以系列浓度经不同剂量的光照后用MTT法测定PDT对肝癌细胞的相对抑制率，流式细胞仪检测其凋亡率．发现随光敏剂浓度的升高和照光剂量的增加，光动力作用对细胞的相对抑制率逐渐增大，在低光动力剂量下明显上升，随后上升渐趋缓慢达平台期．取在特定的光动力剂量下，肝癌细胞出现明显的凋亡现象，与对照组有明显的差异．实验结果表明，光动力作用下对体外培养的人肝癌细胞具有明确的杀伤效应，其机理可能与细胞凋亡有关．     

两亲性光敏剂Al(OH)PcSP在醇水和水溶液中的分子光谱和存在状态

研究了具有光动力抗癌活性的两亲性光敏剂磺基邻苯二甲酰亚胺甲基酞菁羟基铝 (Al(OH)PcSP)在醇水和在水中的电子吸收光谱 ,并探讨了其聚集状态。研究表明 ,Al(OH)PcSP在醇水溶液中以单体形式存在 ,醇的碳链和羟基数对Al(OH)PcSP的单体吸收光谱没有显著的影响。但在水中 ,Al(OH)PcSP存在单体 二聚体平衡 ,二聚平衡常数为 5 730 7× 10 4 mol·L-1。Al(OH)PcSP在水中所形成的二聚体的Q带特征吸收峰位于 740 5nm ,相对于其单体特征吸收峰 (6 76 5nm)红移 ,而一般金属酞菁在水中所形成的聚集体Q带特征吸收光谱均相对于单体兰移至位于 6 30nm附近。研究了Al(OH)PcSP的荧光光谱 ,结果说明 ,二聚体的荧光很弱。     

基于并五苯/酞菁铅异质结的近红外光敏有机场效应管(英文)

采用并五苯(Pentacene)和酞菁铅(PbPc)两种有机材料作为有源层,制备了异质结有机光敏场效应管。在波长为808 nm、强度为124 mW/cm2的近红外光照条件下,异质结phOFET获得最大的光暗电流比达4.4×104,栅压为-50 V时的最大光响应度为118 mA/W,比单层酞菁铅phOFET分别高出766倍和785倍。在经过120 h后,器件的最大光暗电流比和最大光响应度分别稳定于5.4×104和326 mA/W附近。由于在异质结phOFET中采用了对近红外光具有高吸收效率的酞菁铅作为光敏层,而高空穴迁移率的并五苯材料作为靠近栅介质的沟道层,光生载流子的产生与传输能力得到了有效的提高。实验结果表明,基于并五苯/酞菁铅的有机异质结应用于光敏有机场效应管的结构设计中,可以使phOFET成为一种同时具有良好光敏性及稳定性的近红外光探测器件。     

基于超短脉冲的癌细胞荧光光谱

研究用于癌症诊断与治疗的光敏剂血卟啉(hematoporphyrin derivative,HPD)的超快光动力学过程。采用超短脉冲激光光谱技术和皮秒时间相关单光子计数系统,测量经血卟啉培养的活体癌细胞与正常细胞的荧光光谱、荧光寿命特性及荧光峰值强度随时间的变化,观测到:癌细胞样品在645nm处具有特征发射光谱峰;癌细胞与正常细胞样品荧光寿命的快成分分别为150,300ps;癌细胞与正常细胞的荧光峰值强度经12h分别衰减10%和55%。对测量所得的荧光光谱曲线及时间分辨荧光衰减曲线分析,计算出:在癌细胞内部血卟啉浓度增大了约2个数量级;癌细胞与正常细胞的荧光寿命分别为824,1798ps;血卟啉在癌细胞与正常细胞样品中滞留时间分别为17,6d。测量结果确认了荧光光谱技术诊断与治疗癌症的可行性,并对发展超短脉冲激光光谱技术早期诊断与治疗癌症具有重要的指导意义和临床应用价值。     

萘酞菁铅化合物的光限幅特性研究

应用调Q倍频ns/ps Nd：YAG脉冲激光,在波长为532nm,脉冲宽度为8ns,重复频率为1Hz的条件下,研究了溶于二甲基亚砜(DMSO)中的萘酞菁铅溶液的反饱和吸收和光限幅特性。实验表明,萘酞菁铅具有良好的光限幅特性,它的有效激发态吸收截面与基态吸收截面的比值约为15．21,大于萘酞菁铜。研究结果表明,萘酞菁铅的光限幅特性优于C60,激发态吸收是其主要的光限幅机理。实验结果证实了重原子效应可以通过增强系际跃迁而使三重态的反饱和吸收增强,从而提高光限幅的能力。     

基于皮秒时间分辨的癌细胞荧光寿命研究

研究了用于癌症诊断与治疗的光敏剂血卟啉(hematoporphyrin derivative,HPD)的超快光动力学过程,采用超短脉冲激光光谱技术和皮秒时间相关单光子计数系统,测量了经血卟啉培养的活体癌细胞与正常细胞的皮秒时间分辨荧光光谱及荧光峰值强度随时间衰变曲线,观测到：癌细胞与正常细胞样品荧光寿命的快成分分别为150和300 ps;癌细胞与正常细胞的荧光峰值强度经12 h分别衰减10%和55%。经对测量所得的荧光衰减曲线进行分析,计算出癌细胞与正常细胞的荧光寿命分别为824和1798 ps;血卟啉在癌细胞与正常细胞样品中滞留时间分别为17天和6天。结果表明癌细胞与正常细胞对血卟啉亲和性及对血卟啉滞留的稳定性有显著差异,测量结果确认了荧光光谱技术诊断与治疗癌症的可行性,并对实时监测生物样品微弱超快荧光具有重要的指导意义和临床应用价值。     

人肝癌SMMC-7721细胞对低剂量γ射线辐射超敏感性的研究

研究了人肝癌细胞SMMC-7721在低剂量γ射线照射下超敏感性和增强的辐射抗性响应。选用对数生长期细胞接受0—6 Gy不同剂量的^60Coγ射线的照射。利用流式细胞仪对细胞进行分选计数,并用克隆形成法检测细胞存活率。发现SMMC-7721细胞存在低剂量辐射超敏感性和增强的辐射抗性响应,即在0—0．3Gy之间细胞表现出单位剂量杀伤增强现象,在0．3—1Gy细胞表现一定的辐射抗性,在1Gy以上,细胞的存活符合线性平方模型。     

利用PCC技术预测γ射线对肝癌细胞的辐射效应

利用早熟染色体凝集技术预测研究了γ射线对肝癌细胞SMMC-7721的辐射效应。结果表明,G1和G2期细胞内的染色单体和等点染色单体断裂数与照射剂量之间存在线性相关性,染色单体断裂总数与细胞存活率之间存在良好的线性相关性。说明辐射诱导的染色单体断裂可以作为预测SMMC-7721细胞内在辐射敏感性的指标,也可为临床诊断和治疗肝癌提供依据。     

Tuneable magnetic properties of hydrothermally synthesised core/shell CoFe2O4/NiFe2O4 and NiFe2O4/CoFe2O4 nanoparticles

The aim of this study was to prepare a novel targeting nano drug delivery system of 2-methoxyestradiol (2-ME) based on the folic acid-modified bovine serum albumin, in order to improve the clinical application disadvantages and antitumor effect of 2-ME. In this study, 2-methoxyestradiol-loaded albumin nanoparticles (2-ME-BSANPs) were prepared by desolvation method, and then the activated folic acid was conjugated to 2-ME-BSANPs by covalent attachment (2-ME-FA-BSANPs). The size and zeta potential of 2-ME-FA-BSANPs were about 208.8 ± 5.1 nm and ?32.70 ± 1.01 mV, respectively. 2-ME loading efficiency and loading amount of the nanoparticles were 80.49 ± 3.80 and 10.25 ± 1.59 %, respectively. SEM images indicated that 2-ME-FA-BSANPs were of a round shape, similar uniform size, and smooth surface. Studies on drug release indicated that 2-ME-FA-BSANPs had the properties of sustained and controlled release, which provided them with the ability to fight continually against cancer cells. Internalization analysis demonstrated that 2-ME-FA-BSANPs-targeting drug delivery system could get efficiently transferred into the cells through the folic acid-mediated endocytosis, leading to higher apoptosis and affording higher antitumor efficacy against SMMC-7721 cells in vitro compared with 2-ME alone. Furthermore, the cell-cycle arrest of 2-ME-FA-BSANPs on the SMMC-7721 cells occurred at G2/M phase, and 2-ME-FA-BSANPs did not change the inhibition of the tumor mechanisms of 2-ME. Based on these results, it was concluded that albumin nanoparticles could be the promising nano carrier for 2-ME, and 2-ME-FA-BSANPs-targeting drug delivery system may be promising candidate for providing high treatment efficacy with minimal side effects in future cancer therapy.     

利用超分次技术进行肿瘤治疗的探讨

以人类肝癌细胞SMMC-7721和正常肝细胞L02为研究对象，以这两种细胞0．3Gy时超敏感性的存活数据为基础，从理论上探讨了γ射线照射时，用超分次技术治疗肝癌的可能性。经过计算发现:如果目标肿瘤和周围的正常组织超敏感性的存活差异提高到3％，即可利用超分次技术对肿瘤进行治疗。应用超分次进行分次照射时，照射的结果与分次的间隔时间有关。对这一现象的机理进行了一定的探讨，发现时间间隔与细胞G2期的长短可能存在一定的相关性。Based on the survival data of human hepatoma SMMC-7721 and normal liver L02 cells irradiated with γ-rays at 0.3 Gy and 2 Gy, the possibility of uhra-fractionated radiotherapy is discussed in this paper. According to calculations, it is found that if the difference in cell survival between target tumor and adjacent normal tissue is up to 3%, radiotherapy using HRS would be realized through uhra-fractionation. Furthermore, the low-dose response is time-dependent. After analyzing this phenomenon, it was pointed that there would be a correlation between fractionation interval and the duration of cell G2 phase.     

ANXA2 enhances the progression of hepatocellular carcinoma via remodeling the cell motility associated structures

Hepatocellular carcinoma (HCC) ranks as the fifth most common malignancy worldwide. The detailed mechanism of signal regulation for HCC progression is still not known, and the high motility of cancer cells is known as a core property for cancer progression maintenance. Annexin A2 (ANXA2), a calcium-dependent phospholipids binding protein is highly expressed in HCC. To study the roles the excessively expressed ANXA2 during the progression of HCC, we inhibited the ANXA2 expression in SMMC-7721 cells using RNAi, followed by the analysis of cell growth, apoptosis and cell motility. To explore the relationship between the cell behaviors and its structures, the microstructure changes were observed under fluorescence microscopy, laser scanning confocal microscopy and electron microscopy. Our findings demonstrated that down-regulation of ANXA2 results in decreased the cell proliferation and motility, enhanced apoptosis, suppressed cell pseudopodia/filopodia, inhibited expression of F-actin and β-tubulin, and inhibited or depolymerized Lamin B. The cell contact inhibition was also analyzed in the paper. Take together, our results indicate that ANXA2 plays an important role to enhance the malignant behaviors of HCC cells, and the enhancement is closely based on its remodeling to cell structures.     

细胞的原子力显微镜最佳成像条件研究

通过对不同处理条件和测试条件下人肝癌细胞SMMC-7721的原子力显微镜图像的分析和研究,得到了在大气环境和溶液环境中肝癌SMMC-7721细胞的最佳成像条件,同时建立了用原子力显微镜观测活细胞的实验方法.使用0.5%、1%、1.5%的戊二醛溶液固定细胞后再漂洗,变换原子力显微镜的扫描模式,调节扫描参量并在大气环境下观测以寻找该环境下的最佳成像条件；将用多聚赖氨酸处理基底后的培养细胞直接放置于生理溶液中用原子力显微镜进行溶液环境观测,比较扫描时限并分别改变环境液体类型、探针以及扫描频率,比较了不同条件下原子力显微镜图像的差异,在得出最优参量的同时对其相关原理进行了分析,建立了活细胞实时观测的实验方法.比较两种条件下的细胞图像发现,戊二醛溶液固定过的细胞与生理溶液环境中的活细胞有很大差别,在生理溶液条件下的细胞饱满,可见到光滑清晰的细胞边缘；但戊二醛溶液固定的细胞表面粗糙,细胞边缘不清晰,表明固定后观测到的细胞与生理状态下活细胞的表面形貌存在很大差异.     

拉曼光谱研究复方鹿仙草颗粒对SMMC-7721肝癌细胞的作用

应用拉曼光谱研究了不同浓度的鹿仙草溶液与肝癌细胞SMMC-7721的相互作用,通过对药物作用前后细胞的光谱变化进行分析,从而为阐明鹿仙草与肝癌细胞的作用方式提供重要的依据。拉曼光谱显示,加入鹿仙草后,细胞的许多峰都发生了变化。归属于磷酸骨架振动的785和1 092 cm-1的两个峰强度下降,对应碱基A和G的峰1 312和1 585 cm-1 等也有不同程度的降低,表明鹿仙草可能插入DNA碱基对之间,使DNA复制受到抑制,导致细胞DNA含量下降,而且会引起DNA单、双链的断裂。同时,研究还发现属于蛋白质的振动峰(1 005, 1 360, 1 656 cm-1)强度也有不同程度下降,说明蛋白质二级结构以及侧链氨基酸的环境均发生了改变。此外,鹿仙草对细胞的作用效果随浓度增加逐步增强。     

Immobilization of silver nanoparticles in Zr-based MOFs: induction of apoptosis in cancer cells

Silver nanoparticles (AgNPs) are a potential class of nanomaterial for antibiosis and chemotherapeutic effects against human carcinoma cells. However, the DNA-damaging ability of free AgNPs pose the critical issues in their biomedical applications. Herein, we demonstrated a facile method to capture Ag⁺ ions and reduce them into active AgNPs within Zr-based metal-organic frameworks (MOFs) of UiO-66 with a mild reductant of DMF (AgNPs@UiO-66(DMF)). The average diameters of UiO-66 carriers and AgNPs were facilely controlled to be 140 and 10 nm, respectively. The obtained UiO-66 nanocarriers exhibited excellent biocompatibility and could be effectively endocytosed by cancer cells. Additionally, the AgNPs@UiO-66(DMF) could rapidly release Ag⁺ ions and efficiently inhibit the growth of cancer cells. The half maximal inhibitory concentration (IC₅₀) values of the encapsulated AgNPs were calculated to be 2.7 and 2.45 μg mL^?1 for SMMC-7721 and HeLa cells, respectively, which were much lower than those of free AgNPs in the reported works. Therefore, the developed AgNPs@UiO-66(DMF) not only maintained the therapeutic effect against cancer cells but also reduced the dosage of free AgNPs in chemotherapy treatment.

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Graphical abstract A mild reduction process was developed for the fabrication of AgNPs@UiO-66, which exhibited efficient induction of apoptosis in cancer cells.

     

氯胺铂配合物结构和理化特性的研究

采用X射线衍射、傅里叶变换红外光谱和元素分析对合成的几种胺铂配合物的结构、理化特性进行了研究元素分析结果和理论计算一致红外光谱结果表明官能团配位与结构相符X射线衍射分析表示该类化合物均属斜方晶系实验选用黑色素瘤(LiBr)做为外胚层模型,白血病细胞K₅₆₂做为中胚层模型,肝癌(7721)做为内胚层模型通过用MTT法对这几种铂类配合物抑制肿瘤细胞生长效果的测试结果表明,胺铂配合对肿瘤细胞的杀伤作用与浓度梯度和胺配体密切相关随着铂配合物浓度的增加,抗癌效果明显增强随着胺配体的不同,对不同肿瘤细胞的杀伤作用不同.     

Copper hexadecafluoro phthalocyanine and naphthalocyanine: The role of shake up excitations in the interpretation and electronic distinction of high-resolution X-ray photoelectron spectroscopy measurements

We present the first high-resolution X-ray photoelectron core level spectra of bulk copper hexadecafluoro phthalocyanine (CuFPC) and naphthalocyanine (H₂NPC). The measurements have been performed in UHV onto samples grown in situ. A shake-up satellite assigned to a monopole on-site HOMO–LUMO molecular excitation has been evidenced in the F, C and N core-level spectra measured. In the case of the CuFPC, the shake-up is characteristic of the F atoms, of the four N atoms that are Cu bonded, and of the F- and N-bonded C atoms. The shake-up to main peak relative binding energy has been estimated to be 1.6 eV. In the case of H₂NPC, the outer benzenic C atoms do not show a satellite excitation, which instead is characteristic of the C and N atoms belonging to the inner porphyrin-like central ring of the molecule. The shake-up is less than 1 eV at higher binding energies from the main core line. The localisation of the HOMO level in the central structure of the molecule is confirmed by Hartree–Fock all-electron molecular orbital calculations performed on the metal-free phthalocyanine (H₂PC) and hexadecafluoro phthalocyanine (H₂FPC) molecules.