高分散共轭聚合物-金属有机框架纳米立方体的制备及抗肿瘤应用

纳米尺寸的金属有机框架材料兼具传统框架材料的规整孔隙、高比表面积,和纳米材料在活体中的高渗透和长滞留效应,被广泛应用于药物递送领域.然而,单纯递送化疗药物对肿瘤的治疗效果有限,通常需要联合其他治疗方式以提高治疗效果.本工作开发了一种普适的合成方案,用于共轭聚合物-沸石咪唑酯骨架-8(ZIF-8)复合纳米立方体的制备.借助表面活性剂十六烷基三甲基溴化铵,将疏水共轭聚合物聚[2,6-(4,4-双-(2-乙基己基)-4H-环戊二烯并[2,1-b;3,4-b’]二噻吩)-alt-4,7(2,1,3-苯并噻二唑)](PCPDTBT)包裹在ZIF-8中,得到大小约60 nm的纳米立方体.接着,通过两亲性嵌段共聚物F127的修饰实现其在水溶液中的高分散性和胶体稳定性.该复合材料能够高效负载抗肿瘤药物阿霉素并实现酸响应的药物释放,有助于肿瘤的化疗.同时,ZIF-8的包裹也将PCPDTBT的光热转换效率大幅提升至42.5%,可用于高效的光热治疗.动物实验表明,通过化疗和光热治疗的联合,载药后的复合纳米立方体能够在激光照射下显著抑制肿瘤的生长且不会对正常组织造成明显损伤,是一种高效的抗肿瘤试剂.     

稀土上转换多功能复合材料的构建及生物应用进展

镧系离子(Ln³⁺)掺杂的稀土上转换纳米材料在低能近红外光激发下可发射高能量的紫外、可见甚至近红外光，由于其独特的光学和化学性质，包括自荧光弱、对生物体光损伤小及组织穿透深度高等，稀土上转换纳米材料在生物医学领域的应用备受关注.在该综述中，主要介绍了本课题组在稀土上转换纳米发光材料的自组装、复合材料的构建及在肿瘤诊疗领域的相关工作，重点强调设计、合成多种刺激-响应型的多功能纳米诊疗平台，利用肿瘤微环境的特点（乏氧、偏酸性、富含H₂O₂和谷胱甘肽）和近红外光的独特优势，实现纳米材料在肿瘤部位的靶向蓄积、药物的选择性控制释放和协同肿瘤治疗（化疗、光动力治疗、光热治疗及免疫治疗等）.     

铋基纳米材料在癌症成像诊断与治疗中的应用

随着纳米医学的快速发展,纳米诊疗材料因其兼具诊断和治疗等多功能性而受到越来越多的关注.铋(Bi)基纳米材料具有优异的光学、电学和磁学性质,在肿瘤的诊疗一体化领域具有广阔的应用前景.我们总结了Bi基纳米材料常用的构建方法,重点介绍了其在计算机断层扫描(CT)成像、光声(PA)成像、放射疗法(RT)、光热疗法(PTT)及协...     

ZIF-8@PDMAPMA复合材料的构筑及其性能研究

采用分步法(路线I)和一步法(路线II和路线III)分别合成了金属有机框架(MOFs)/高分子复合材料(ZIF-8@PDMAPMA),并采用粉末X射线衍射(PXRD)、傅里叶变换红外光谱(FTIR)、扫描电子显微镜(SEM)、透射电子显微镜(TEM)和热重分析(TGA)等对其进行了表征.ZIF-8@PDMAPMA复合材料由高分子柔性链包覆ZIF-8晶体颗粒形成核壳纳米颗粒,探讨了不同合成方法对其形貌的影响.ZIF-8@PDMAPMA纳米颗粒呈球状或类似ZIF-8晶体形状轮廓.反应体系中单体、有机配体以及反应过程中形成的高分子链均具有乳化作用,实现了对复合纳米材料粒径及其分布的有效控制,粒径仅50 nm,且分布均一.高分子柔性链对MOFs晶体颗粒的有效包裹导致ZIF-8@PDMAPMA对N_2吸附能力减弱.ZIF-8@PDMAPMA亲水性明显增强,从而使其在水中的分散性和稳定性得到明显改善,且粒径分布均一.同时,实现了ZIF-8@PDMAPMA对苯扎氯铵的有效负载和可控释放,最大负载量达到0.05 g/g,且释放率达到82%.动力学模拟结果显示,复合材料内部的ZIF-8的孔隙和表面的高分子柔性链对苯扎氯铵具有多层吸附行为.高分子柔性链与刚性MOFs晶体有效结合,极大地改善了MOFs在水相中的稳定性,并将进一步拓宽其应用范围和领域.     

多功能肿瘤诊疗一体化的金纳米材料的研究进展

由于良好的生物相容性以及在可见或近红外光区独特的表面等离子体共振(surface plasmon resonance,SPR)性质,金纳米材料体系是目前纳米科学研究领域的一个耀眼的明星体系,该体系在生物医学领域有着广泛的应用.金纳米材料制备简单、形状和尺寸可控,其光学性质如表面增强拉曼散射效应和易于调节至生物体的"透明窗"——近红外区的SPR效应,适合用于诊断检测、成像以及肿瘤光热治疗等.金纳米结构还可以作为载体,载带基因/化疗药物和荧光分子,进行化疗、荧光成像及光动力治疗等.可见,金纳米结构能够同时实现肿瘤的诊断与治疗,为精准医疗的发展提供了新思路.本文重点介绍了几种金纳米结构材料在肿瘤诊疗一体化方面的研究进展.     

基于金属纳米材料的癌症光热切除疗法

在癌症治疗中,传统的手术疗法、放射疗法和化学疗法会伤害到体内正常的组织以及带来一些其他的副作用,因此新的治疗手段,如在近红外激光中利用感光增强布光热切除疗法（PTA）已经开始被研究应用于癌症治疗.在当前新兴的纳米科学领域中,有许多相关的研究成果被认为可以作为新的纳米技术手段直接应用于癌症的检测和治疗中.光热切除疗法（PTA）的基本原理是在激光照射条件下,利用光热转换产生的高热量来破坏消除癌细胞,其中,在癌细胞位点上强的光照吸收以及高的光热转换效率是光热切除疗法（PTA）能否成功实施的关键.在贵金属纳米材料中,如金纳米颗粒和银纳米颗粒,由于他们对光具有很强的表面等离子共振吸收效应,因而他们可以在光热切除疗法（PTA）应用中有效地增强光热转换效率,而且关于金属纳米材料的结构优化以及其相关的光热转换性质的研究目前也已经有了显著的成果.在光热切除疗法中,理想的纳米金属材料应该具有下列一些特征：具有强的以及可调的表面等离子共振吸收、容易传输、毒性低以及容易与目标癌细胞结合.在这篇综合评述文章中,我们将主要讲述包括金纳米颗粒、纳米棒、纳米壳结构、纳米笼状结构以及纳米空心球结构等不同结构的金纳米材料在光热切除疗法（PTA）应用中的研究.在这些不同结构的纳米材料中,金纳米空心球由于具有较小的尺寸（30～50nm）和球状结构,以及很强的、并且半峰宽较窄的可调节的表面等离子共振效应,因此在光热切除疗法（PTA）中表现出最佳的综合性质.     

纳米药物载体结合分子靶向在肿瘤化疗中的应用

纳米技术与肿瘤治疗中的化学疗法相结合具有广阔的应用前景,应用纳米技术设计药物载体递送化疗药物已经成为当前人类攻克肿瘤研究的一个重要手段。纳米药物载体与肿瘤靶向在化疗方面的应用,能够有效改善化疗药物水溶性和稳定性,提高药物利用率和抗肿瘤活性,降低对机体正常细胞组织的毒副作用,克服多药耐药性问题,进而提高肿瘤化疗效果和促进肿瘤化疗的发展进步。本文着重综述纳米药物载体系统及其靶向策略方面的研究现状与进展,并探讨纳米技术与化疗相结合攻克肿瘤的应用前景。     

多功能纳米佐剂在肿瘤疫苗中的应用

作为一种新的治疗策略,免疫疗法已发展成为继手术、化疗和放疗之后的第四种肿瘤治疗手段,并展现出良好的应用前景。肿瘤免疫治疗的方法种类繁多,其中将纳米技术应用于治疗性的肿瘤疫苗,极大地提高了疫苗的效应。本文介绍了纳米佐剂在肿瘤疫苗中的多种功能,重点介绍了几种纳米粒子的合成方法和疫苗治疗效果,总结了纳米技术用于肿瘤免疫治疗的一些新思路,并对应用纳米技术解决肿瘤疫苗面临的挑战进行了初步的分析和展望。     

动态变构纳米组装体的设计、合成及生物医药应用

纳米技术对生物医药学的发展具有重要的推动作用.如何构建新型纳米材料,实现其在疾病部位生物功能的最优化,是当今纳米生物医药领域的关键问题.智能型纳米组装体作为一类能够在特定刺激下发生响应性功能转变的纳米材料,在该领域中受到了极大的关注.尤其是在肿瘤等疾病的诊断与治疗中,结合肿瘤微环境特征,设计与合成能够根据体内过程调整结构的动态变构纳米组装体,以达到成像信号放大、治疗效果增强以及安全性提升的目的,为建立智能化诊疗方案提供了新策略.本文主要讨论了纳米组装体的常用制备策略,集中探讨了对内源性刺激响应(pH、酶、氧化还原等)的动态变构纳米组装体在肿瘤诊疗中的应用.     

能量转换纳米医学和生物材料

传统癌症治疗方法(如化疗、放疗和手术切除等)存在对正常组织的严重毒副作用和治疗效果差等缺点,从而阻碍了其在临床治疗中的进一步应用.随着纳米技术和纳米医学的快速发展,能量转换生物材料介导的治疗方式,由于其具有非侵入性、较强的组织穿透能力和对治疗剂量的精准调控等优势而受到广泛关注和研究.本文总结了近年来本研究团队在"能量转换生物材料"(包括光-热转换、光-化学能转换、超声-化学能、超声-热能转换、磁-热能转换和化学能-化学能转换)的设计、制备及其在癌症治疗中的应用,并讨论了"能量转换纳米医学和生物材料"在未来临床转化中的应用前景和面临的挑战.     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.     

A general and convenient synthesis of 4-(tosylmethyl)semicarbazones and their use in amidoalkylation of hydrogen,heteroatom, and carbon nucleophiles

A general synthesis of previously unknown semicarbazone-based α-amidoalkylating reagents, 4-(tosylmethyl)semicarbazones, has been developed. The synthesis involved three-component condensation of semicarbazones of aliphatic or aromatic aldehydes with the same or other aldehydes and p-toluenesulfinic acid. The scope and limitations of this reaction were investigated. The compounds obtained were demonstrated to be an efficient α-(4-semicarbazono)alkylating agents. They were reacted with H- (sodium borohydride), O- (sodium methylate), S- (sodium phenylthiolate), N- (pyrrolidine, sodium succinimide), P- (trialkyl phosphites), and C-nucleophiles (sodium diethyl malonate) to give the corresponding products of the tosyl group substitution, 4-substituted semicarbazones, including analogues of nitrofurazone. Among the prepared compounds tested in vitro for antibacterial and antifungal activity, three nitrofuryl-containing semicarbazones exhibited high biological activities with minimum inhibitory concentration (MIC) values of 8–32 μg/mL.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

Synthesis of novel chiral bidentate hydroxyalkyl-N-heterocyclic carbene ligands and their application in palladium-catalyzed Mizoroki–Heck couplings and asymmetric addition of diethylzinc to benzaldehyde

A small library of new chiral bidentate hydroxyalkyl-imidazolium salts 1 is conveniently synthesized on multi-gram scale from inexpensive and commercially available chiral pool amino acids. The corresponding carbenes, generated by deprotonation of imidazolium salts 1, in combination with palladium(II) chloride were tested in the Mizoroki–Heck coupling reaction. The most significant results in terms of yields and reactivities were achieved with low catalyst loading. The catalytic activities of these imidazolium salts were also investigated in the asymmetric addition of diethylzinc to benzaldehyde. The use of MgO nanoparticles as an additive in conjunction with these ligands played a crucial role in increasing the efficiency of these reactions.     

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.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Microwave-assisted copper-catalyzed stereoselective ring expansion of three-membered heterocycles with α-diazo-β-dicarbonyl compounds

Microwave-assisted copper-catalyzed ring expansions of three-membered heterocycles with α-diazo-β-dicarbonyl compounds were investigated. Thiiranes generated 3-acyl-5,6-dihydro-1,4-oxathiines in the presence of copper sulfate and trans-3-acyl-5,6-dihydro-1,4-oxathiines as stereospecific products for 1,2-disubstituted cis-thiiranes through an intramolecular S_N2 process. Oxiranes gave rise to 2-acyl-5,6-dihydro-1,4-dioxines under the catalysis of copper hexafluoroacetylacetonate and cis-3-acyl-5,6-dihydro-1,4-dioxines as stereospecific products for 1,2-disubstituted cis-oxiranes via an intimate ion-pair mechanism. The current method provides a direct and simple strategy in efficient preparation of 3-acyl-5,6-dihydro-1,4-oxathiines and 2-acyl-5,6-dihydro-1,4-dioxines, important agents in medicinal and agricultural chemistry, from readily available thiiranes and oxiranes, respectively.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.