α-环糊精/聚乙二醇自组装超分子纳米药物载体

研究了一种新型超分子纳米药物载体的制备方法及其药物释放性能. 将α-环糊精(α-CD)穿入肉桂酸改性的PEG分子链形成包含复合物(inclusion complex, IC), 通过超分子自组装成为纳米粒子. 将抗肿瘤药物阿霉素负载到纳米粒子中, 研究药物释放行为及其对肿瘤细胞的抑制效果. 以核磁共振(1H NMR)、X射线衍射(XRD)、紫外吸收光谱(UV)、动态光散射(DLS)、扫描电镜(SEM)、透射电镜(TEM)和原子力显微镜(AFM)表征了纳米粒子的结构和形貌, 用激光共聚焦显微镜(Confocal)研究了载药纳米粒子在细胞内的分布及其对肿瘤细胞的抑制效果. 结果显示超分子纳米粒子具有很好的生物相容性和药物缓释作用, 载药纳米粒子对肿瘤细胞具有很好的杀伤效果.     

还原响应型羧甲基纤维素基纳米药物载体的构建及其性能研究

近年来,刺激响应型智能纳米药物载体以其可控的药物释放、毒副作用小等优点,在药物递送领域引起广泛关注。本研究以羧甲基纤维素(CMC)为骨架材料,通过还原性二硫代二丙酰肼(TPH)连接疏水小分子胆酸(CA),合成两亲性高分子聚合物CMC-TPH-CA (CTC)。然后以10-羟基喜树碱(HCPT)为抗肿瘤模型药物,在水溶液中自组装制备CTC/HCPT纳米粒子,并对其物化性质及体外抗肿瘤活性进行了评价。结果表明,CTC/HCPT纳米粒子具有较高的包封率(～87.6%)及载药量(～21.4wt%),适当的粒径大小(～140nm)及低的溶血性(5%)。体外释放结果表明,CTC/HCPT纳米粒子具有明显的还原敏感性。最后,以LLC肿瘤细胞为模型,考察CTC/HCPT纳米粒子的体外细胞毒性。结果表明,相较于纯HCPT,CTC/HCPT纳米粒子的细胞杀伤作用有了明显的提升。     

卡铂@葡聚糖纳米载体的自组装/聚合一步法制备及生物应用

在接枝共聚辅助自组装(GISA)制备葡聚糖纳米载体的过程中, 利用丙烯酸单体与卡铂之间的非共价键作用, 使得卡铂参与到葡聚糖纳米载体的形成中, 从而一步实现了卡铂@葡聚糖纳米载体的制备, 并使用肿瘤还原性环境敏感的二硫键来交联纳米载体, 得到了对肿瘤还原环境响应的纳米药物载体. 对纳米药物载体的结构、 粒径及形貌进行表征, 结果显示, 纳米药物载体粒径为(92±0.2) nm, Zeta电位为(-8±0.3) eV. 通过体外药物释放研究发现, 在还原性环境中, 载体可持续72 h释放药物, 最大释放量达80%. 细胞摄取实验表明负载卡铂的纳米药物载体可在4 h内高效地进入细胞核; 其半抑制浓度(IC₅₀)为25.32 μg/mL, 达到和相同浓度游离卡铂相仿的促肿瘤细胞凋亡效果. 此一步法所制备的卡铂@葡聚糖纳米载体具有良好的生物应用前景.     

微量热法研究蟾蜍甾二烯类化合物对嗜热四膜虫BF5生长代谢的影响

采用微量热法研究中药蟾蜍中4种蟾蜍甾二烯类化合物(BD)对嗜热四膜虫BF5生长代谢的影响.在不同给药条件下,以表达热功率-时间曲线(热谱曲线)的特征参数生长速率常数(k),最大产热功率(Pmax)和半数抑制浓度(IC50)为指标,对4种蟾蜍甾二烯类化合物干预嗜热四膜虫生长代谢程度进行客观的量化评价.结果表明:k和Pmax均随4种蟾蜍甾二烯类化合物浓度的增加而相应减小,且k与不同化合物的相应浓度间有良好的线性关系(r0.98);华蟾毒精、蟾毒灵、蟾毒它灵和日蟾毒它灵的IC50分别为119.2、106.14、73.80和54.75μg·mL-1,即毒性效应大小顺序为日蟾毒它灵蟾毒它灵蟾毒灵华蟾毒精.初步构毒关系研究表明,在蟾蜍甾二烯结构母核C11上引入α-OH,C14上引入β-OH,C16上引入β-OAC以及C14与C15未发生脱水均可明显增加蟾蜍甾二烯对嗜热四膜虫BF5的毒性作用.     

聚乳酸-乙醇酸/纳米氧化锌复合电纺纤维装载亲疏水药物的控释及体外细胞毒性

利用静电纺丝技术制备了负载亲水性药物阿霉素(DOX)以及疏水性药物喜树碱(CPT)的复合纳米纤维. 先用巯基封端的普朗尼克(F127)修饰纳米氧化锌(FZnO), 再将FZnO负载盐酸阿霉素(DOX@FZnO), 最后将DOX@FZnO与CPT一起纺入聚乳酸-乙醇酸(PLGA)纤维中. 体外药物释放结果表明, 复合纳米纤维能够减小亲水性药物的突释, 减缓药物释放速率, 延长药物释放时间. 体外细胞活性结果表明, 双载药复合纤维比单载药复合纤维具有更强的细胞毒性, 能够有效抑制癌细胞生长.     

基于DNA纳米花的细胞自噬基因沉默用于增敏抗肿瘤化疗

自噬是真核细胞降解蛋白质的重要途径之一, 在细胞的更新代谢中起重要作用. 肿瘤细胞借助高水平的细胞自噬能够阻断细胞凋亡途径, 降低化疗药物的抗肿瘤效果. 本文通过设计编码有核酸适配体序列(Aptamer)和DNA酶序列(DNAzyme)的多功能DNA纳米花, 利用DNA序列可负载化疗药物阿霉素(Dox)的特性, 实现了对肿瘤细胞特异靶向的药物递送, 并高效沉默肿瘤细胞的自噬相关基因ATG5, 达到增敏抗肿瘤化疗的效果. 通过RT-PCR实验验证合成的DNA纳米花可以有效剪切肿瘤细胞中自噬相关基因ATG5的mRNA; 并通过DNA纳米花的细胞毒性和细胞凋亡实验研究了其对肿瘤细胞系MCF-7的靶向治疗作用, 结果显示该多功能DNA纳米花在增敏抗肿瘤化疗方面具有明显优势.     

丁二酸酐接枝纳米纤维素负载木犀草素及其苷（英文）

将纳米纤维素(NCC)表面接枝丁二酸酐得到丁二酸酐化纳米纤维素(NCSA),再将阳离子表面活性剂十六烷基三甲基溴化铵(CTAB)负载到NCSA,得到一种新的纳米药物载体(CTAB@NCSA).考察了NCSA的物理化学性能,包括扫描、透射电镜,红外光谱,X射线粉末衍射及电位测定;同时研究了NCSA对CTAB的吸附行为.最后以CTAB@NCSA为药物载体,以LUT和LUS为模型药物,通过分子间作用力及疏水作用力得到负载LUT和LUS的纳米复合物微球CTAB@NCSA@LUT和CTAB@NCSA@LUS,并对其体外释药进行了研究.     

大麻二酚纳米结构脂质载体的制备及其性质研究

通过高压均质法制备包载大麻二酚(CBD)的纳米结构脂质载体(CBD-NLC),并考察其载药量、包封率、平均粒径、Zeta电位、长期储存稳定性等物理化学性质,筛选获得CBD-NLC最佳配方。在优化条件下制备的CBD-NLC平均粒径为163.7±1.3nm,多分散性指数(PDI)为0.14±0.02,包封率和载药量分别为95.5±1.0%和9.8±0.1%。通过透射电镜、傅里叶变换红外光谱、差示量热扫描、X射线衍射对CBD-NLC进行表征,结果表明,CBD被很好地负载在NLC中,CBD-NLC主要为球形结构。与文献报道相比,纳米结构脂质载体能够包载CBD,具有较好的载药量和包封率,可解决CBD的溶解性及稳定性问题,提高CBD的有效利用度。制备的CBD-NLC可用去离子水以任意比例稀释,具有良好的稳定性,便于其在医药产品中的应用。     

pH响应性树枝状聚合物-金纳米粒子复合药物载体的制备

以表面接枝聚乙二醇链的聚酰胺胺树枝状聚合物(PEG-PAMAM)为纳米载体, 在其内部空腔包覆金纳米粒子, 在金纳米粒子表面连接硫辛酸改性的阿霉素(LA-DOX), 从而间接实现了抗癌药物在PEG-PAMAM内的高效负载. 同时, LA-DOX中的酰腙键提供pH响应性, 实现了药物的pH响应性释放. 紫外-可见(UV-Vis)光谱表明, 包覆金纳米粒子的PEG-PAMAM纳米载体对LA-DOX的负载能力显著增强. 体外细胞实验表明, 负载LA-DOX的树枝状聚合物-金纳米粒子复合药物载体具有较强的抗肿瘤能力.     

纳米金属有机框架材料在药物递送领域的应用

金属有机框架材料(Metal-Organic Frameworks, MOFs)是一类由金属离子及有机配体自组装而成的多孔材料,具有孔隙率高、比表面积大和结构多样化等独特优点,广泛应用于气体储存、物质分离和催化等领域。纳米尺寸金属有机框架材料(Nanoscale Metal-Organic Frameworks, NMOFs)既保持了传统MOFs的规整性,也具有纳米颗粒的特殊性质,在生物医药领域中是绝佳的药物载体。相比于传统纳米药物载体,NMOFs与药物的结合方式丰富,展现了多种药物装载模式,可以满足不同药物的制备需求,也可引入不同功能分子优化性能。最近,有越来越多的研究报道了多功能化NMOFs应用于药物递送领域,并实现刺激响应性的可控释放。本文将着重对NMOFs材料作为药物载体负载抗癌药物、光敏剂和核酸的应用进展进行综述。     

甘草次酸修饰PEG-PLGA纳米粒的制备及与肝癌细胞的亲和性

将肝靶向分子甘草次酸偶联至聚乙二醇-聚(乳酸-羟基乙酸)(PEG-PLGA)嵌段共聚物上.以聚乙二醇维生素 E(TPGS) 为稳定剂,采用溶剂挥发法制备肝靶向纳米粒子,通过核磁共振、红外光谱、激光光散射及透射电镜等方法对共聚物及纳米粒子的理化性质进行表征;运用噻唑蓝(MTT)比色法评价纳米粒子作为药物载体的安全性,并通...     

Synthesis,characterization and cytotoxicity of Pt(II), Pd(II), Cu(II) and Zn(II) complexes with 4’‐substituted terpyridine

Eight novel Pt(II), Pd(II), Cu(II) and Zn(II) complexes with 4’‐substituted terpyridine were synthesized and characterized by elemental analysis, UV, IR, NMR, electron paramagnetic resonance, high‐resolution mass spectrometry and molar conductivity measurements. The cytotoxicity of these complexes against HL‐60, BGC‐823, KB and Bel‐7402 cell lines was evaluated by MTT assay. All the complexes displayed cytotoxicity with low IC₅₀ values (<20 μm ) and showed selectivity. Complexes 3 , 5 , 7 and 8 exerted 9‐, 5‐, 12‐ and 7‐fold higher cytotoxicity than cisplatin against Bel‐7402 cell line. The cytotoxicity of complexes 3 , 5 , 6 , 7 and 8 was higher than that of cisplatin against BGC‐823 cell line. Complexes 3 , 7 and 8 showed similar cytotoxicity to cisplatin against KB cell line. Complex 7 exhibited higher cytotoxicity than cisplatin against HL‐60 cell line. Among these complexes, complex 7 demonstrated the highest in vitro cytotoxicity, with IC₅₀ values of 1.62, 3.59, 2.28 and 0.63 μm against HL‐60, BGC‐823, Bel‐7402 and KB cells lines, respectively. The results suggest that the cytotoxicity of these complexes is related to the nature of the terminal group of the ligand, the metal center and the leaving groups. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis,characterization, and cytotoxicity of complexes of platinum(II) with 2,2′-bipyridine and N-benzoyl-L-amino acid dianion

Four new platinum(II) complexes (1–4) with N-benzoyl-L-amino acid and bipy were synthesized and characterized by elemental analysis, IR, UV, ¹H NMR, and mass spectra. The crystal structure of 1 was determined by X-ray diffraction analysis. Cytotoxicities were measured by MTT and SRB assays. Complexes 1–4 exert cytotoxicity with selectivity against HL-60, Bel-7402, BGC-823, and KB cell lines. This suggests that amino acids and acylated groups have important effects on cytotoxicity; the cytotoxicity is also related to the species of tumor cells, but the IC₅₀ values do not show definite correlation with the variation of amino acids and acylated groups.     

新型钯配合物[Pd(Phen)(TsserNO)]·H_2O的合成、晶体结构和体外抗肿瘤活性(英文)

A novel palladium(Ⅱ) complex [Pd(Phen)(TsserNO)]·H2O (Phen=1,10-phenanthroline; TsserNO=4- toluenesulfonyl-L-serinate dianion) has been prepared and structurally characterized, the cytotoxicity in vitro has also been investigated by MTT and SRB assays. The complex crystallizes in the monoclinic system, space group P21 with cell parameters a=0.618 64(14) nm, b=1.768 9(4) nm, c=0.990 2(2) nm, β=102.392(4)°, V=1.058 3(4) nm3 and Z=2. The complex had selectivity against HL-60, BGC-823, Bel-7402 and KB cells lines, its cytotoxicity is equal to that of cisplatin against BGC-823 and Bel-7402 cells lines, however it is less potent than cisplatin against HL-60 and KB cell lines.Keywordsantitumor; palladium(Ⅱ) complex; crystal structure     

Improvement of transfection efficiency by galactosylated N-3-guanidinopropyl methacrylamide-co-poly (ethylene glycol) methacrylate copolymers

GalactosylatedN-3-guanidinopropylmethacrylamide-co-poly (ethylene glycol) methacrylate copolymers (galactosylated GPMA-co-PEGMA, GGP) were developed in order to promote transfection efficiency in the presence of serum in this report. First of all, the galactosylated PEGMA-co-GPMA copolymers were prepared via aqueous reversible addition – fragmentation chain transfer polymerization (RAFT) of poly (ethylene glycol) methacrylate (PEGMA) with long circulating chain segment and N-3-aminopropyl methacrylamide (APMA) followed by galactosylation and guanidinylation. After that, GGP/plasmid DNA complexes were examined by a dynamic light scattering and gel electrophoresis. It is showed that GGP copolymers have effective condensing ability. The cytotoxicity of GGP was measured by MTT assay. It was found that all the GGP/plasmid DNA complexes had less cytotoxic effects on HepG2 cells than HeLa cells, and the galactose groups reduced the cytotoxicity of complexes with high charge ratios to HepG2 cells. Finally, the transfection efficiency of the galactosylated PEGMA-co-GPMA copolymers was investigated by luciferase expression assay. The results revealed that the copolymers with galactose groups more than 5.83% could induce the asialoglycoprotein (ASGP) receptor mediated transfection, which improved the transfection efficiency in target cells. The GPMA-co-PEGMA copolymers with 54.57% hydrophilic chain segment PEG should prevent the aggregation of protein on the GGP/pDNA complexes, and GGP with 7.94% galactose graft exhibited the highest transfection in the presence of serum.     

Synthesis,characterization, and cytotoxicity of mixed-ligand complexes of platinum(II) with 2,2′-bipyridine and 4-toluenesulfonyl-L-amino acid dianion

Five new platinum(II) complexes (1–5) with 4-toluenesulfonyl-L-amino acid dianion and 2,2′-bipyridine (bipy) have been synthesized and characterized by elemental analysis, IR, UV, ¹H-NMR, ¹³C-NMR, and mass spectra. The crystal structure of 1 has been determined by X-ray diffraction analysis. Cytotoxicity was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. The results indicate that 1–5 exert cytotoxic effects with selectivity against tested carcinoma cell lines; 5 displays better cytotoxicity against BGC-823, Bel-7402, and KB cell lines, while 1 has better cytotoxicity against KB cell line. The 4-toluenesulfonyl- L-amino acid dianions have important effects on cytotoxicity; when 4-toluenesulfonyl-L-amino acid dianions are 4-toluenesulfonyl-L-glycine and 4-toluenesulfonyl-L-phenylalanine, the complexes show better cytotoxicity.     

The dose-effect of icariin on the proliferation and osteogenic differentiation of human bone mesenchymal stem cells

Icariin had been reported as a potential agent for osteogenesis, but the dose-effect relationship needed further research to realize the clinical application of icariin. We isolated and purified human bone mesenchymal stem cells (hBMSCs) and stimulated them with different concentrations of icariin. The cytotoxicity of icariin was evaluated by the methylthiazolytetrazolium (MTT) assay method. The proliferation and osteogenic differentiation of such hBMSCs were investigated for different concentrations of icariin. We found that icariin had a dose-dependent effect on the proliferation and osteogenic differentiation of hBMSCs in a suitable concentration range from 10(-9) M to 10(-6) M, but at concentrations above 10(-5) M, the cytotoxicity limited its use. The extremely low cost of icariin and its high abundance make it appealing for bone regeneration.     

Cytotoxicity activity,in silico molecular docking,protein- and DNA-binding study of a new Ni(II) Schiff base complex

Abstract

One new nickel(II) complex, [Ni(L)] (1), was synthesized from the Schiff base ligand derived from pyrrole-2-carboxaldehyde and 1,3-diaminopropane. Complex 1 was characterized by elemental analysis, IR, UV-Vis and ESI mass spectroscopy, cyclic voltammetry, and single-crystal X-ray structure analysis. Crystallographic results show that two Ni(II) monomeric moieties are present with similar structural features but with slightly different bond lengths and bond angles. The geometry around the Ni(II) center is distorted square planar. DNA-binding properties of complex 1 were well explored by employing UV-Vis and fluorescence spectral methods, cyclic voltammetry, and by viscosity measurements. Similarly the protein-binding study was studied by multispectroscopic techniques using both BSA and HSA. The cytotoxicity study of the compound has also been evaluated. Notably, the in vitro cytotoxicity of complex 1 on two cancer cell lines (AGS and A549) demonstrates that complex 1 has very good anticancer activity. MTT assay, cell-cycle analysis, and annexin-V assay have been performed to know the extent of effect of complex 1 as anticancer agent. Further, in silico molecular docking study revealed that the nickel(II) complex fits into the minor groove of duplex DNA by hydrophobic interaction with functional groups of B-DNA.     

N,N-二(8-黄酮甲基)香叶胺类化合物的合成及生理活性

设计合成了4个N,N-二（8-黄酮甲基）香叶胺类化合物,所有目标化合物的结构均经1H NMR、MS和元素分析测试技术确证。采用MTT法考察了目标化合物对K562（白血病细胞）和SMMC7721（肝癌细胞）2种肿瘤细胞的体外抑制活性,结果表明,所测化合物对2种肿瘤细胞都有体外抑制活性,其中N,N-二(3′,4′-二甲氧基-8-黄酮甲基）香叶胺(1c)的活性最好,IC50值分别为5.78和3.85 μmol/L,N,N-二（4′-氟-8-黄酮甲基）香叶胺(1a)和化合物1c对K562（白血病细胞）的体外抑制活性明显优于商品药物美法仑(Melphalan)。以溴化乙锭(EB)为荧光探针测定了化合物1c与鲱魚精DNA有较强的相互作用。     

芳香亚胺与N-(4-甲基苯甲酰)-L-缬氨酸双阴离子合钯(Ⅱ)配合物的合成、晶体结构及体外抗肿瘤活性

本文首次报道了2个钯(Ⅱ)的配合物[Pd(bipy)(4-CH3Bzval-N,O)](1)和[Pd(phen)(4-CH3Bzval-N,O)](2)(bipy=2,2′-联吡啶,phen=1,10-菲咯啉,4-CH3Bzval-N,O=N-(4-甲基苯甲酰)-L-缬氨酸双阴离子)的合成及晶体结构,利用MTT法和SRB法研究了配合物的体外抗肿瘤活性。配合物2属单斜晶系P21/n空间群,其中a=1.162 92(8)nm,b=1.074 03(7)nm,c=1.821 14(12)nm,V=2.232 8(3)nm3,Z=4。结果显示:2个配合物对HL-60,BGC-823,Bel-7402和KB 4种人的肿瘤细胞表现出一定的活性和选择性,但其活性均小于顺铂。