透明质酸纳米材料在荧光/光声成像和光疗中的应用

荧光/光声成像和光疗技术的生物医学应用引起了人们越来越多的关注, 然而很多荧光/光声造影剂存在生物相容性较差, 缺乏肿瘤靶向性, 信噪比较低, 功能单一等共性问题, 严重限制其诊疗应用. 透明质酸具有优异的生物相容性和主动肿瘤靶向性, 可被透明质酸酶降解, 并且易于化学修饰和实现多种超分子弱相互作用力协同工作. 因此, 人们将透明质酸与荧光/光声造影剂结合制备纳米材料, 使其在细胞乃至活体的标记性能和治疗效果获得了很大的改善. 本文综述了将两类物质结合制备纳米材料的方法, 着重阐述了纳米材料的结构与性能关系, 为其未来设计和开发提供了指导, 最后对存在的主要问题以及未来的重要研究方向进行了分析和展望.     

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.     

可控释放一氧化碳的纳米材料及其生物医学应用

一氧化碳（CO）是一种内源性气体信使分子,具有广泛而复杂的生理学功能.CO分子的生理学效应与其浓度、位置和作用时间密切相关.而现有的一氧化碳供体普遍存在着稳定性较差,剂量难以把控,缺乏靶向性以及对正常细胞和组织器官具有潜在的毒副作用等问题,限制了其进一步的应用.随着纳米科学技术的迅速发展,国内外研究者们构建出一系列能够实现可控释放CO的多功能纳米材料,并将其用于生物医学领域.结合纳米材料自身独特的性能优势,分类介绍了多种内源性/外源性刺激响应型CO控释纳米材料,并概述了可控释放CO的纳米药物在抑制炎症反应、抗菌和肿瘤治疗等生物医学领域的应用,最后对CO控释纳米材料在生物医学领域面临的挑战和发展前景进行了总结和讨论.     

核酸适体-纳米材料复合物用于癌症的诊断与靶向治疗研究进展

因具有独特的光、电、磁、热等优异性能,纳米材料已被广泛应用于生物分析与生物医学领域。核酸适体是一类能够高亲和力和高特异性地与靶标结合的寡核苷酸序列。将核酸适体作为识别单元与纳米材料相结合,可以构建核酸适体-纳米材料复合物。近年来,在肿瘤靶向治疗方面,核酸适体-纳米材料复合物受到了人们的广泛关注。通过纳米材料与具有特异性识别能力的核酸适体的结合,核酸适体-纳米材料复合物可以为癌症治疗提供一种更有效的、低毒副作用的新策略。本文综述了核酸适体-纳米材料复合物作为药物输送载体在癌症的特异性识别与诊断及靶向治疗方面的应用。除此之外,本文还总结了核酸适体-纳米材料复合物与其他新兴技术的有效结合从而提高选择性和癌症治疗效率的相关研究进展。     

无机纳米-生物界面作用的SERS研究

探索生命体对无机纳米材料的生物应答机制是高效、安全、可控地应用无机纳米材料的基础,其关键在于准确理解在生物体系中无机纳米材料与生物分子间的纳米.生物界面作用.本文主要探讨了在纳米-生物界面具有拉曼增强效应的金、银纳米材料;介绍了表面增强拉曼光谱(surface-enhanced raman spectroscopy,SERS)原位研究金、银等无机纳米材料表/界面吸附的核酸、蛋白质、磷脂等生物分子,以及细胞、病毒和细菌等与金、银纳米材料表/界面作用的研究进展;综述了SERS技术在探索纳米-生物界面作用机制、生物分子测定、生物分子界面行为监测中的应用.     

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.     

生物细胞仿生药物递送系统在癌症治疗中的应用

纳米药物在癌症的精准医疗方面具有广阔的应用前景,但纳米材料易被机体免疫系统识别并清除的特性使得其在癌症治疗方面的应用存在很大的局限性.受自然界生物系统的启发,生物细胞介导的药物递送系统近年来得到了广泛关注.该技术通过将生物体内源性细胞膜作为功能材料包覆在纳米药物表面,赋予其细胞膜的天然属性,或者将纳米载药粒子直接与活细胞共孵育,制备载药细胞,有效地将生物体"自体"的性质与"人工"纳米材料的优势相结合.这不仅大大降低了纳米药物的免疫原性,延长其血液循环时间,而且还可使其具备更强的肿瘤靶向能力.本文初步探讨了生物细胞仿生药物递送系统在肿瘤治疗中的研究进展并对其未来研究进行展望.     

用于肿瘤综合治疗的无机纳米材料

无机纳米材料以其独特的纳米特性,在以肿瘤为代表的多种疾病的诊疗一体及综合治疗中具有越来越广泛的应用。本文重点关注该领域代表性的三类材料：超顺磁性氧化铁纳米粒、上转换纳米粒以及贵金属纳米粒,它们分别具有优异的磁学性能、光学性能及热性能,归纳总结了它们在体外检测、活体成像、药物输送以及靶向治疗等方面的应用及其优势与劣势,希望为发展生物相容性更好、诊疗效果更佳的无机纳米材料提供更好参考和建议,促进无机纳米材料的临床转化。     

肿瘤微环境响应药物递送系统的设计

化学药物治疗(化疗)是目前临床上治疗肿瘤最有效的方法之一,但传统的给药方式导致药物对肿瘤的靶向性差、药物利用率低。在杀伤肿瘤细胞的同时,化疗药物对人体正常细胞也有很大的损伤,因此在化疗过程中通常伴随着严重的副作用,例如恶心、呕吐以及脱发等。随着肿瘤学和纳米材料的迅速发展,多种纳米药物载体被应用于肿瘤的治疗。纳米药物载体具有提高药物利用率、降低药物的毒副作用等诸多优势,已成为药物递送领域的研究热点。其中,肿瘤微环境响应纳米药物载体在实现肿瘤部位药物的可控释放、载体保护壳的脱除以及肿瘤靶向等方面表现出优异的性能。本文讨论了基于肿瘤微环境的异常生化指标构建肿瘤微环境响应载体的常用策略,并总结了近年来肿瘤微环境响应纳米药物载体用于肿瘤治疗的研究进展,旨在为设计与制备高性能纳米药物载体提供参考。     

抗肿瘤纳米材料

<正>蓬勃发展的纳米材料为肿瘤的安全高效治疗提供了有潜力的平台,其主要应用于肿瘤精确诊断、药物靶向递送、微环境调控和自身免疫系统激活等方面^[1-2]。本文简述了该领域发表于《应用化学》上的最新研究成果,并展望了抗肿瘤纳米材料在临床应用中的机遇与挑战。     

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.     

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.     

Cu0-catalysed 1,3-dipolar cycloadditions of α-amino acid derived N,N-cyclic azomethine imines to ynones

A series of 20 CuAIAC reactions between eight 4-acylamino substituted pyrazolidine-3-one-1-azomethine imines and four terminal ynones were performed using Cu⁰ as catalyst. The corresponding fluorescent cycloadducts were obtained in very high yields upon simple workup. Thus, Cu-metal turned out to be a better catalyst than Cu^I in terms of yield and ease of isolation. Availability of azomethine imines, mild reaction conditions, and simple workup enable a “click” access to libraries of densely substituted 2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-ones. Reactivity of differently substituted dipoles was evaluated experimentally and by quantum chemical methods (DFT).     

Synthesis and antioxidative/anti-inflammatory activity of novel fullerene–polyamine conjugates

(E)-4-(Fullerenopyrrolidin-1-yl)-3-methylbut-2-enoic acid and its corresponding succinimidyl ester, readily obtained through Prato-type modification of C₆₀, were used for the selective N-acylation of polyamines. The thus obtained conjugates were evaluated for their antioxidative and anti-inflammatory activity and their cytotoxicity was determined. Members of this family of compounds showed interesting anti-lipid peroxidation, anti-lipoxygenase and anti-inflammatory activity and comparable cytocompatibility to spermidine.     

Copper-catalyzed multicomponent reactions of 2-iodoanilines,benzylamines, and elemental sulfur toward 2-arylbenzothiazoles

A relatively cheap copper salt-catalyzed, three-component approach providing 2-arylbenzothiazoles in good to excellent yields from readily available 2-iodoanilines, benzylamines, and sulfur powder is reported. This methodology allows preparation of various classes of 2-arylbenzothiazoles and provides a general, reliable approach.