体内自组装多肽纳米材料及其在肿瘤诊疗中的研究进展

多肽纳米药物由于具有易于设计改造、良好的靶向性、生物相容性和较长的血液循环时间等优势,在生物医学与肿瘤诊疗中具有巨大的潜力.近年来,利用肿瘤微环境原位构建多肽纳米材料的策略已被广泛研究,本文综述了多肽纳米材料通过不同的刺激响应(pH、酶和氧化还原等)实现体内自组装,从而对肿瘤的诊断与治疗产生的积极效果.重点阐述了不同的刺激响应型自组装多肽纳米材料的设计合成及其在肿瘤诊疗中的应用,如对于药物递送系统中的药物富集、渗透和内吞等过程的增强作用,同时简单介绍了其在生物成像上的应用,最后对体内自组装多肽纳米材料的未来发展进行了展望.     

基于多肽的药物递送系统研究进展

药物递送系统是将药物输送到药物作用靶点的系统,理想的递送系统可以提高药物作用效果并降低给药剂量和毒副作用.本文综述了药物递送系统中的多肽类药物递送系统的研究进展.多肽具有易合成、易代谢、免疫原性低、毒副作用低等优点,多肽支链上大量的官能团可以和药物偶联,是药物递送系统的重要发展方向.本文从靶向肽、穿透肽、响应肽和组装肽四个方面介绍了多肽药物递送系统的原理和实例.组装肽可以形成纳米结构,显著提升多肽药物递送系统的稳定性,可以实现长效释放.组装肽体内原位调控进一步增加了多肽药物递送系统的智能型、精准性,展现出巨大的转化潜力.     

基于靶向调控肿瘤微环境的多肽纳米药物系统研究进展

肿瘤微环境在肿瘤的发生、发展和转移过程中起着至关重要的作用,因此靶向调控微环境为发展肿瘤精准治疗的新策略提供了机遇。纳米技术的快速发展为传统药物的增效减毒提供了契机,已有一系列纳米药物用于肿瘤临床治疗。近年来,分子自组装领域的快速发展为智能纳米药物的研发提供了新机遇。多肽作为生物相容性高、序列可设计、易修饰、功能多样化的生物分子,可组装构建结构多样和功能集成的纳米药物系统。本文综述了利用多肽自组装超分子体系实现药物对肿瘤微环境的响应释放和高效递送,并对其通过调控微环境中的血管、成纤维细胞和胞外基质等组分,改变肿瘤赖以生存的"土壤",并与抗肿瘤细胞治疗有机结合的最新进展进行了介绍。针对肿瘤异质性和复杂性的难题,构建表/界面性质可控的纳米药物系统,发展基于肿瘤微环境调控与联合治疗的肿瘤综合治疗方案,将是未来重要的发展方向之一。     

可控自组装DNA折纸结构作为药物载体的研究进展

在过去的几十年里, DNA纳米技术作为一种快速发展的可控自组装技术, 使人们能构建出各种复杂的纳米结构. DNA折纸结构具备可编程性、 空间可寻址性、 易修饰性及良好的生物相容性等多种优越的特性, 这些优异的性质使其在药物递送方面具有广阔的应用前景. 本文总结了近年来可控自组装DNA折纸结构作为药物递送系统的研究进展, 展望了DNA折纸纳米载体未来的发展方向, 并讨论了该领域面临的挑战和可能的解决方法.     

肽基纳米材料及其应用

近年来,肽类超分子自组装合成纳米材料受到了广泛研究和关注,已成为纳米材料科学研究的前沿领域之一。肽基纳米材料因其良好的生物相容性以及结构和功能的多样性,在材料学、组织工程、生物工程及药物传递等方面展示出巨大的应用潜力。本文综述了肽类自组装纳米材料制备的最新研究进展,重点介绍了疏水性二肽、类表面活性剂多肽、Aβ多肽片段、烷基链修饰多肽等通过非共价键作用自组装形成的不同结构的纳米材料,包括纳米管、纳米纤维、纳米囊/球、纳米水凝胶等;同时,介绍了多肽自组装机理模型及其分子动力学模拟方面取得的研究成果;最后总结了肽基纳米材料在金属/半导体材料、生物传感器、组织修复材料及药物传递等领域的应用现状及今后重点研究的方向。     

环境响应性多肽自组装研究进展

分子自组装广泛存在于自然界中,参与生物体的各项生命活动,从而确保生物体相关生理功能的实现和生化反应的有序进行.多肽自组装作为分子自组装的重要组成部分,其良好的生物相容性为构建具有重要应用价值的生物医用材料提供了新的思路.本文总结了多肽自组装过程中主要的驱动作用力;简述了多肽自组装形成的主要结构;详细介绍了自组装过程中环境变化,包括pH、温度、离子强度、特殊离子、氧化还原态以及光照等,对于环境响应性多肽自组装结构和性质的影响;并且阐述了多肽自组装生物材料的应用方向和前景,希望为该领域的进一步研究提供参考.     

介孔二氧化硅基智能递送体系的构建及其在各类疾病治疗中的应用

利用先进纳米技术开发的药物递送体系能够改善药物的理化性质和治疗效果,同时削弱其毒副作用,因而纳米药物递送体系成为现代药剂学研究的热点和主流方向。其中,介孔二氧化硅作为纳米载体的基质材料具有比表面积大、形貌结构可调、表面易于修饰及生物相容性良好等优点,引发生物医学研究人员的广泛关注,为构筑新型智能药物递送体系提供了新的设计思路。本文就介孔二氧化硅基智能递送体系在设计构筑和疾病治疗应用等方面的最新研究进展进行了综述。首先,本文对介孔硅的发展历程、制备方法及结构特性进行了简要概述;其次,从药物装载和门控释放两大角度系统阐述了近些年介孔硅基智能递送体系的构建策略,重点介绍了各种刺激响应性介孔硅基递送体系的门控开关(如聚合物、无机纳米颗粒、超分子组装体及生物大分子等)及其可控释放机制;随后,详细描述了介孔硅基控释体系在各种类型疾病(包括癌症、细菌感染、糖尿病和阿尔茨海默病等)治疗中的应用进展;最后,总结和分析了介孔硅基智能纳米载体研究中存在的问题并对其未来发展作了展望。     

多肽分子自组装

源于自然界中广泛存在的蛋白质自组装现象,近年来多肽的自组装逐渐成为材料学和生物医学等领域的研究热点.通过合理调控多肽的分子结构以及改变外界的环境,多肽分子可以利用氢键、疏水性作用、π-π堆积作用等非共价键力自发或触发地自组装形成形态与结构特异的组装体.由于多肽自身具有良好的生物相容性和可控的降解性能,利用多肽自组装技术构建的各种功能性材料在药物控制释放、组织工程支架材料以及生物矿化等领域内有着巨大的应用前景.本文总结了近年来多肽自组装研究的进展,介绍了多肽自组装技术常见的几种结构模型,概括了多肽自组装的机理,并进一步阐述多肽自组装形成的组装体形态及其在材料学和生物医学等领域里的应用.     

多肽自组装技术及其在生物医学上的应用

多肽分子自组装广泛存在于自然界中。多肽具有良好的生物相容性和可调控的降解性能,并且利用多肽自组装技术,可以在分子水平上设计并调控聚集态的形状和结构,这在生物医学材料方面具有巨大的应用潜力。近年来关于多肽自组装的研究成为材料学、医学等领域中研究热点之一,并且在药物缓释载体、组织工程支架研究方面取得进展。本文介绍多肽分子自组装技术的概念,综述了多肽自组装技术在药物缓释载体材料、组织工程支架材料方面的应用。     

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。     

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%.     

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.     

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.     

Selective syntheses of 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones via temperature-dependent Rh(II)-carbenoid-mediated 2H-azirine-ring expansion

The Rh(II)-catalyzed reaction of 2-carbonyl-substituted 2H-azirines with ethyl 2-cyano-2-diazoacetate or 2-diazo-3,3,3-trifluoropropionate provides an easy access to 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones. These compounds can be selectively prepared from the same starting material using temperature as the only varied parameter. The 2-azabuta-1,3-diene intermediate, a common precursor for both heterocyclic products, isomerizes into 2H-1,3-oxazine under kinetic control, while 1H-pyrrol-3(2H)-one is the sole product of the reaction at elevated temperatures. According to DFT-calculations a one-atom oxazine ring contraction involving ring-opening to a 2-azabuta-1,3-diene intermediate, followed by a 1,5- and 1,2-prototropic shift leads to the consecutive formation of imidoylketene and azomethine ylide, which then further undergo cyclization to the pyrrole derivative.     

Copper catalyzed/mediated synthetic methodology for ebselen and related isoselenazolones

Scope of the copper catalyzed/mediated selenium-nitrogen coupling reaction has been studied for the synthesis of isoselenazolones. It is noticed that the 2-chloro, 2-bromo-, and 2-iodo-aryl amides substrates can be exploited in the selenium-nitrogen coupling reaction by employing 25-100 mol % of CuI/1,10-phenanthroline (L) and potassium carbonate as a base in DMF. Furthermore, electron rich 2-chloro-arylamides also underwent selenium-nitrogen coupling reaction to give biologically important selenium-nitrogen heterocycles. Also, copper-catalyzed selenium-nitrogen coupling reaction has been meticulously applied for the synthesis of diaryl diselenides having methoxy, amine, and amide functionality from respective aryl iodides in the presence of stoichiometric amount of succinimide as an external Se-N coupling partner.     

Knoevenagel condensation catalyzed by novel Nmm-based ionic liquids in water

A series of novel N-methyl morpholine (Nmm) based ionic liquids with 1,2-propanediol group were synthesized and used as catalysts for Knoevenagel condensation at room temperature in water. Under the effect of the catalyst, various aldehydes or aliphatic ketones could react with a wide range of activated methylene compounds well, including malononitrile, alkyl cyanoacetate, cyanoacetamide, β-diketone, barbituric acid, 2-arylacetonitrile and thiazolidinedione. Furthermore, most of the products could be separated just by filtrating and washing with water. Additionally, the catalyst is recyclable and applicable for the large-scale synthesis.     

Construction of polyheterocyclic spirotetrahydrothiophene derivatives via sulfa-Michael/aldol cascade reaction

A series of polyheterocyclic spirotetrahydrothiophene derivatives were obtained in moderate to excellent yields via a catalyst-free sulfa-Michael/aldol cascade reaction of chalcones 1 and commercially available 1,4-dithiane-2,5-diol 2 under mild conditions. We also present the first asymmetric sulfa-Michael/aldol cascade reaction of chalcones 1 and commercially available 1,4-dithiane-2,5-diol 2 with moderate to good enantioselectivities catalyzed by readily available chiral phase-transfer catalysts (PTCs).     

Suzuki-Miyaura reactions of the soluble guanylate cyclase inhibitor NS2028: a non-product specific route to C-8 substituted analogues

Both soluble guanylate cyclase (sGC) inhibitors ODQ 1 and NS2028 2 are synthesized via improved protocols. In the former case treating 3,4-dihydroquinoxalin-2(1H)-one oxime 8, which can be prepared in two steps from 1,2-benzenediamine, with 1,1′-carbonyldiimidazole (CDI) gives the dihydro-ODQ 10 that in the presence of KMnO₄ oxidises to give ODQ 1 in an overall yield of 46% starting from 1,2-benzenediamine. In the latter case, the synthesis affords NS2028 2 from 2-amino-4-bromophenol 3 in three steps with an overall yield of 85% and avoids the need for chromatography. Furthermore, Suzuki-Miyaura reaction conditions are described that enable the preparation of 8-aryl and 8-heteroaryl derivatives of NS2028 directly from NS2028 2. Finally, demethylation of the 8-(methoxyphenyl) substituted analogues afforded the 8-(hydroxyphenyl) derivatives 40-42. All new products are fully characterised.