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.     

双刺激响应型纳米载药系统的构建及性能

采用聚乙二醇单甲醚(mPEG)为亲水段,聚赖氨酸(PzLL)为疏水段,通过二硫键和碳氮双键串联桥连合成了两嵌段共聚物(mPEG-CN-SS-PzLL),其中的二硫键具有还原敏感性,碳氮双键具有pH酸敏感性。通过红外光谱和核磁共振谱等手段测试分析了产物的化学结构。将聚合物通过透析法自组装制备得到双刺激响应型纳米载药粒子。结果表明:该纳米载药粒子的药物包封率较高,达到52%。该载药系统在还原环境或酸性环境下具有良好的体外释药性能。     

葡萄糖响应苯硼酸接枝壳聚糖盐酸盐抗肿瘤药物载体

通过分子改性向壳聚糖盐酸盐高分子链中引入苯硼酸基,合成了双亲性化合物苯硼酸接枝壳聚糖盐酸盐.细胞毒性实验表明苯硼酸接枝壳聚糖盐酸盐具有良好的细胞相容性.该双亲性化合物能够自组装成胶束聚集体,并包封疏水药物.以阿霉素为模型药物,研究了载药胶束聚集体的体外药物释放行为,结果表明,阿霉素在载药胶束聚集体内能够持续释放,且具有葡萄糖响应性.在生理p H=7.4和固体肿瘤弱酸性(p H=6.5)条件下,药物的释放速度十分缓慢,而当释放介质中有葡萄糖存在时,药物释放速度都明显加快.     

壳聚糖的改性及其纳米粒子的制备

通过壳聚糖上的氨基与硬脂酸和硫辛酸的羧基脱水缩合反应,将硬脂酸和硫辛酸接枝在壳聚糖上,引入的疏水性基团使修饰的壳聚糖具有两亲性。对修饰壳聚糖残留的自由氨基进行甲基化,使氨基的pKa值由6.6增加到6.8~7.1。修饰的壳聚糖在水介质中经超声分散即可形成纳米粒子,纳米粒子的Zeta电位为正值,说明修饰壳聚糖中残留的氨基和甲基化的氨基处于纳米粒子的表面。纳米粒子经二硫苏糖醇还原,然后经空气中的氧气氧化,在纳米粒子中形成二硫键交联结构。     

pH敏感性叶酸修饰羧甲基壳聚糖纳米粒子作为紫杉醇载体的研究

将活化的叶酸分子连接到O-羧甲基壳聚糖(O-CMCS)上.以CaCl2为交联剂,通过离子交联法制备叶酸修饰的O-CMCS纳米粒子(FCC NPs),并开展了从FCC NPs作为抗癌药物紫杉醇(PTX)载体的研究.结果表明:FCC NPs呈球形,粒子大小约190 nm,对PTX的载药量和包封率均受PTX加入量的影响.该纳米粒子对药物的释放具有较好的pH敏感性,能够增强PTX在癌细胞处的富集.同时,该纳米粒子无细胞毒性,纳米粒子表面由于叶酸的存在使其具有较好的细胞靶向性,且载药纳米粒子对癌细胞生长具有良好的抑制作用.     

荧光介孔二氧化硅纳米粒子的合成及药物运输（英文）

合成了荧光介孔二氧化硅纳米粒子(MSNs-FITC),并研究了其在持续药物释放和生物示踪成像方面的应用。首先,采用一步法合成出MSNs-FITC,结合SEM、TEM、FT-IR、XRD和氮气吸附脱附等表征技术进行表征。其次,将抗癌药物阿霉素(DOX)负载到MSNs-FITC中。载药粒子的药物释放行为具有明显的pH依赖性,酸性环境加速释放速率。同时,体外细胞毒性测试表明MSNs-FITC具有良好的生物相容性。激光共聚焦扫描显微镜(CLSM)图像表明,MSNs-FITC可以进入细胞并具有剂量依赖性,流式细胞术分析(FCM)进一步证明了这一结果。     

核交联的含磺酸甜菜碱pH敏感胶束的制备与表征

制备了一种在疏水段带有侧基叠氮官能团的两亲性pH敏感的聚合物——聚己内酯-聚(甲基丙烯酸二乙氨基乙酯-磺酸甜菜碱)((PCL-ACL)-PDEAS);同时合成了两端带有炔基中间带有二硫键的交联剂,用红外、核磁表征了目标分子.通过两亲性高分子自组装形成胶束,并通过点击化学反应获得了核交联的胶束.通过动态光散射测定粒径,胶束酸碱滴定表征胶束的pH敏感性,还原条件下释放药物的速度,对比了非交联胶束和交联胶束的性质.结果表明,交联胶束在正常生理条件下的释放速度比未交联胶束更慢;而在有DTT的存在条件下,交联胶束由于二硫键断裂,释放速率明显加快.因此,核交联载药胶束有可能响应肿瘤的微环境实现靶向释放.     

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.     

葡聚糖分子量和接枝度对阿霉素/白蛋白-葡聚糖纳米粒子体外抗肿瘤效果的影响

以Maillard反应制备的牛血清白蛋白-葡聚糖共价接枝物作为载体, 通过调节混合溶液的pH值和温度制备负载阿霉素的白蛋白-葡聚糖纳米粒子. 利用分子量为5×10³, 10×10³和62×10³的葡聚糖制备了多种共价接枝物, 研究了共价接枝物分子量对载药纳米粒子的粒径和稳定性及载药量的影响. 用短链葡聚糖(分子量5×10³和10×10³)制备的纳米粒子粒径为60 nm左右, 用长链葡聚糖(分子量62×10³)制备的纳米粒子粒径约为200 nm; 阿霉素的包埋效率为81%~98%, 包埋量为7.4%~16.9%. 细胞实验结果表明, 共价接枝物具有很好的生物相容性; 与自由阿霉素相比, 纳米粒子可以促进阿霉素进入人口腔上皮癌细胞; 受缓释性质的影响, 纳米粒子在低浓度时的细胞毒性要小于自由阿霉素. 与长链葡聚糖纳米粒子相比, 接枝度高的短链葡聚糖纳米粒子由于具有较小的粒径、 密集的葡聚糖分子刷表面、 一定的自由阿霉素浓度和较快的阿霉素释放速率, 因而更容易进入细胞并具有更好的体外抗肿瘤活性.     

抗癌载药体系Fe_3O_4@ZIF-8@PA的合成及药物释放

采用溶剂热法合成磁性Fe_3O_4纳米粒子,并以此为基底设计制备了一种具有pH响应核壳结构的磁性纳米复合材料Fe_3O_4@ZIF-8@PA.该材料的比饱和磁化强度可达35.46 A·m2/g,具有良好的磁性.Fe_3O_4纳米粒子呈球型结构,分散性良好.与基底相比,复合微球的粒径尺寸明显增大,但依然符合载体材料的理想尺寸且分布均匀.此外,载体具有多孔结构,表面积较大,载药效率和载药量分别高达96.4%和144.6 mg/g.在pH为7.4和5.0的条件下对载药纳米粒子进行了药物释放研究.24 h内,粒子在2种pH下累计释放量分别为39.8%和78.6%.通过药物缓释验证了载体的pH响应性能.在实验中引入了对癌细胞具有杀伤作用的植酸,使合成的载体具有一定的抗癌作用.同时采用四甲基偶氮唑盐(MTT)法对人骨肉瘤细胞(MG-63)进行了体外分析实验,证实材料与抗癌药物阿霉素(DOX)之间存在着一定的协同抗癌效果.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

A carbanion induced synthesis of highly congested pyrazole and imidazole containing heterocycles

An efficient approach to the synthesis of highly congested di, penta and hexacyclic pyrazoles as well as imidazole fragment containing novel heterocyclic molecule has been developed through a carbanion induced transformation of suitably functionalized 2H-pyran-2-ones, benzo[h]chromene and thiochromeno[4,3-b]pyrans. Due to the presence of fluorescence, we report their prime application metal sensor as off/on switching in ferric ions.     

Synthesis of pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles by Curtius reaction in Morita-Baylis-Hillman derivatives

Synthesis of substituted pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles from the Morita-Baylis-Hillman derivatives of acrylates via saponification followed by Curtius reaction is described.     

正丁胺对激光染料荧光谱影响的研究

用正丁胺作为碳源,采用射频辉光放电制备碳膜,选用激光染料R6G和聚乙二醇混合液作为蒸气源,采用单源热蒸发,在蒸发室与染料同时沉积得到混合膜,用拉曼光谱和红外光谱分析了碳膜的结构和键合方式,分析表明:碳膜中存在胺基团和氢原子.混合膜的荧光谱测量结果表明,认为正丁胺对染料荧光谱的影响是因为胺基和氢原子的存在.     

Selective synthesis of 4,5-dihydroimidazo- and imidazo[1,5-a]quinoxalines via modified Pictet–Spengler reaction

An efficient tandem approach for the selective synthesis of 4,5-dihydroimidazo[1,5-a]quinoxalines 6a–g and imidazo[1,5-a]quinoxalines 7a–h by the reaction of 2-imidazolyl anilines 4a–c with aryl aldehydes 5a–k under mild reaction conditions is described. Introduction of electron releasing alkyl groups in substrates 4a–b was found to be instrumental for the success of the reaction.     

Understanding the Diels-Alder reactivity of 1,2-azaborine analogues

The Diels-Alder reactivity of 1,2-heteroborines (H₄C₄B(H)X, X?=?NH, PH, AsH; O, S, Se) has been computationally explored by means of Density Functional Theory (DFT) calculations. The influence of the HB?=?X fragment on the reactivity of the system has been quantitatively analyzed in detail by means of the so-called Activation Strain Model (ASM) of reactivity. It is found that the interaction between these species and the dienophile is significantly stronger than that computed for their all-carbon isoelectronic counterpart, benzene. In addition, the strain energy plays a key role in the observed reactivity trends. The role of the aromaticity strength of these heteroarenes on the reactivity is also assessed.