微纳米马达的运动控制及其在精准医疗中的应用

人工微纳米马达是模仿自然界中的生物马达制备而成的微纳尺度动力装置,具有稳定性高、制备简单、可批量生产等优点,在生物医学领域有广阔的应用前景.本文详细阐述了磁能、电能、声能、光能及热能等多种微纳米马达的运动控制方式,总结了其在核酸、蛋白质、细胞以及细菌等的装载、运输、释放和检测方面的研究进展,并讨论了其在精准医疗领域面临的挑战和未来的发展方向.     

基于微/纳马达的智能癌症诊断、递送及治疗

癌症严重威胁着人类的生命健康,早期的诊断和治疗对于提高癌症治愈率、挽救人们的生命有着至关重要的作用。随着纳米科技的发展,具有自主运动性能的微/纳马达为癌症的诊断与治疗带来了新的发展契机。微/纳马达能够有效地将多种能量(光、声、磁、电、热等)转化为自身运动的动能,有望在微米或纳米空间内执行各种复杂而精确的任务,这在智能化癌症诊疗领域具有得天独厚的优势。目前,已成功制备出不同形状的微/纳马达,比如线状马达、微管马达、Janus双面神结构马达等,促进了一系列新型诊断方法、胞内递送系统及光治疗策略等的发展。本文主要总结了微/纳马达在智能化癌症诊疗领域的研究进展,首先从化学场驱动与物理场驱动这两个角度总结了微/纳马达在检测和靶向递送方面的最新研究进展,并进一步总结了微/纳马达在癌症光治疗领域的应用进展,最后探讨了目前存在的问题及未来的发展方向。     

微纳米马达在药物递送中的应用

受到自然界中高效生物马达的启发,研究人员提出了人工微纳米马达的概念,即人工微纳米动力装置。目前,通过结合化学与其他交叉学科的先进技术,研究人员已制备出具有不同结构、驱动方式以及控制方式的人工微纳米马达。这些微纳米马达在传感、环境治理、生物医用等方面展现出广阔的应用前景。其中,药物递送是生物医用领域的重要方向。在这一方面,利用微纳米马达可以实现药物的有效递送,给癌症等疾病的治疗带来新的可能。本文将针对用于药物递送的微纳米马达的驱动机理、基本结构、运动控制这几个方面进行综述,首先介绍了马达的运动机理,其驱动机理可分为自场驱动和外场驱动;其次,分别介绍了可用于药物递送的微纳米马达的结构,主要包括聚合物囊泡、空心管、纳米线等;为了实现精准有效的药物递送,微纳米马达的可控运动非常重要,本文将具体阐述微纳米马达的开-关控制、方向控制和速度控制。最后,分析了药物递送微纳米马达的研究现状,并对本领域的未来方向进行了展望。     

面向疾病应用的微纳米马达

微纳米马达是能将环境中的化学反应或外场(光、声、磁场、电场等)提供的能量转化为推进力,从而产生自主运动的微纳米级人造机器。由于具有集群效应、比表面积大、运动可控等多种特征,微纳米马达在环境修复、药物递送、微纳手术、抗感染、重金属清除等诸多领域受到关注。在一定条件下,微纳米马达能主动运动并聚集到病灶,将治疗或诊断药物递送到靶部位,有望在人体复杂环境中进行精细化的工作。因此,微纳米马达在疾病预防、诊断、治疗以及预后中具有巨大的发展空间。在此,本综述首先对微纳米马达进行简要介绍,包括其结构设计、驱动方式。其次,详细介绍微纳米马达在不同类型的疾病中的研究进展。最后,提出目前该技术面临的挑战与未来发展方向。     

卷曲管状微马达的调控和应用

通过纳米薄膜自卷曲技术制备而成的微马达因其简便的制备方法、优秀的物理化学性能而在材料科学、化学、生物学等领域有广阔的应用前景.这种微马达从外界获取能量,实现了在低雷诺数环境下模仿自然界中的生物运动.本文详细介绍了自卷曲微米管的制备工艺和运动控制(包括速度控制和方向控制),并综述了近几年微马达应用于化学、生物医药、环境科学等领域的研究成果.     

生物酶驱动的微纳米马达在生物医学领域的应用

生物酶驱动微纳米马达是指利用天然酶催化分解过氧化氢、葡萄糖、尿素和甘油酯等燃料来提供动力的一种新型微纳米机器。生物酶驱动的微纳米马达具有良好的生物相容性,能够在原位利用生物燃料实现自主靶向运动,无需外加原料,这使得生物酶驱动的微纳米马达在生物医学领域展现出巨大的发展潜力与前景。目前,生物酶驱动的微纳米马达在生物医学领域的应用得到众多科学家的关注,但是时至今日,还没有一篇及时、全面、着重地讨论生物酶驱动微纳米马达在生物医学领域应用的综述文章。基于本课题组的研究经验以及目前该领域的发展情况,本文着重讨论不同种类生物酶驱动微纳米马达在疾病诊疗等生物医学领域应用的最新进展,包括生物标志物的检测与诊断、成像显像剂、癌症和其他疾病的治疗等。最后,本文对该领域的发展与未来研究方向提出展望,为实现以“面向世界科技前沿、面向人民生命健康”为目标的“人类卫生健康共同体”提供新的思路和方向。     

甘露糖修饰的微马达的制备及其免疫功能初探

为了开发集自驱动运动与免疫功能于一体的新型糖杂化材料,本工作设计并制备了一种甘露糖修饰的哑铃形微马达(Zincoxide/Polydopamine/Mannose微马达,简称ZnO/PDA/Man微马达),其不对称的哑铃结构会引起不均匀的离子分布,从而促使马达运动.该马达能量来源无生物毒性,能够在可见光的照射下,以纯水为燃料,实现离子型自扩散泳运动.通过调节可见光的强度和辐照方向,可实现马达运动速度和方向的精准调控.ZnO/PDA/Man微马达具有良好的生物相容性,且表面修饰生物活性的甘露糖苷可作为免疫激活剂使巨噬细胞极化.相比于传统免疫激活剂,ZnO/PDA/Man微马达有望在可见光照射下,实现肿瘤组织中的自由运动和深度渗透,在肿瘤免疫治疗领域具有潜在的应用价值.     

胶体马达

胶体马达亦称微纳米马达、微纳米泳体或游动纳米机器人,是研究复杂系统的绝佳非平衡态物理模型,同时因其具有额外的自推进力、自主导航等独特优势,有望为靶向药物递送等生物医学应用带来颠覆性变革.作为一个新兴的多学科交叉领域,胶体马达拓展了胶体与界面化学的研究范畴,带来了新的现象、理论与应用,是以胶体科学为核心的国际前沿交叉学科研究的热点领域.本文系统地阐述了胶体马达以及基于胶体马达的超分子胶体马达和游动纳米机器人的新概念,同时以本课题组在胶体马达领域取得的研究成果为例,详细综述了胶体马达的结构设计与可控制备、驱动机理及运动行为的界面调控策略、集群行为规律与重构方法以及突破各种生物屏障实现药物主动靶向递送等方面的最新进展,在此基础上展望了胶体马达对于胶体科学发展所带来的新机遇与新挑战.     

微纳马达的聚集与分散行为及其机理解析

微纳马达是一种能被多种能量(化学能、光能、声能、电能、磁能等)激活而发生运动(旋转、穿梭、聚集、扩散等)且尺寸为微米或纳米级的功能器件。其具有体积较小、可控性好、制备简单等优点,在诸如纳米自组装、聚合物降解、药物运输、水污染治理等多个领域展现出较好的应用前景。微纳马达的聚集与分散行为是马达非常重要的群体行为,聚集状态下可大幅提升马达执行任务的效率,分散状态下又可成为独立的个体,各自运动,执行各自的使命。本文概述了近年来微纳马达在聚集与分散行为方面的重要研究进展和最新研究成果,详细叙述不同刺激下两者之间的转换过程及其机理,为深入开展微纳马达动态行为的科学研究提供一定的借鉴和参考。     

自由流电泳芯片研究进展

20世纪提出的自由流电泳不仅可应用于有机生物分析,也可应用于无机化合物分析。它的连续样品制备、分析条件温和等优点使其在在线监测和检测应用中引起研究者的兴趣。随着微机械加工技术的发展,几种微流控自由流电泳芯片(μ-FFE)相继被提出并通过实验得到表征,使得在几秒内进行快速分离以及μL体积的样品分离成为可能。本文对这类新型的分离技术的设计和应用进行了综述。     

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.     

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.     

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.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.     

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.     

Chemistry of heterocyclic compounds at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, over 50 years (Review)

The review contains a concise historical account and information on the most significant researches undertaken by the staff at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences on the Chemistry of Heterocyclic Compounds. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his 70th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1443–1502, October, 2008.     

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.     

Sulfur-directed metal-free and regiospecific methyl C(sp3)–H imidation of thioanisoles

Regiospecific and direct imidation of the methyl C(sp³)–H bond of thioanisoles is realized under mild and metal-free conditions with N-fluorobis(benzenesulfonyl)imide as an oxidant and nitrogen source. Proposed mechanism suggests that thionium ion intermediates and a Pummerer-type reaction are involved. The imidation has advantages such as high step-economy, excellent functionality tolerance, and regiospecificity, giving structurally diverse imidation products.     

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.