Bioconjugation

生物缀合
  • 文章类型: Journal Article
    核酸通过靶向涉及癌症和遗传疾病的各种细胞信号传导途径提供了有希望的治疗平台。然而,在交付过程中保持最佳稳定性限制了它们的效用。核酸递送载体通常分为生物和合成载体。不管生物载体的效率如何,如病毒载体,与它们的免疫原性和致癌作用有关的问题对于临床应用非常重要和至关重要。另一方面,合成载体,如脂质或聚合物,已广泛用于核酸递送。尽管它们的转染效率,储存稳定性低,瞄准低效率,和跟踪限制是这些载体临床应用的限制之一。在过去的几十年里,具有独特性质的金纳米粒子已被证明是克服这些障碍的高效矿物载体。在这次审查中,我们专注于金纳米颗粒-核酸组合,并强调它们在治疗各种类型癌症中的应用。此外,通过说明这些结构的生物学应用,我们将讨论它们的临床应用。
    Nucleic acids provide a promising therapeutic platform by targeting various cell signaling pathways involved in cancer and genetic disorders. However, maintaining optimal stability during delivery limits their utility. Nucleic acid delivery vehicles are generally categorized into biological and synthetic carriers. Regardless of the efficiency of biological vectors, such as viral vectors, issues related to their immunogenicity and carcinogenesis are very important and vital for clinical applications. On the other hand, synthetic vectors such as lipids or polymers, have been widely used for nucleic acid delivery. Despite their transfection efficiency, low storage stability, targeting inefficiency, and tracking limitations are among the limitations of the clinical application of these vectors. In the past decades, gold nanoparticles with unique properties have been shown to be highly efficient mineral vectors for overcoming these obstacles. In this review, we focus on gold nanoparticle-nucleic acid combinations and highlight their use in the treatment of various types of cancers. Furthermore, by stating the biological applications of these structures, we will discuss their clinical applications.
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  • 文章类型: Journal Article
    在过去的几十年里,用于治疗目的的分子实体的复杂性继续发展。主要的推进剂加油创新是制药行业的永久任务,以满足新疾病领域和/或交付挑战的需求。随着新的作用机制被发现,随着我们对现有机制的理解的增长,需要和/或利用以使治疗发展的性质继续扩大。一个快速发展的关注领域是化学增强的肽和蛋白质治疗剂。虽然各种缀合分子如抗体-药物缀合物,肽/蛋白质-PEG缀合物,和蛋白质结合疫苗已经很成熟,其他人,例如使用非PEG聚合物的抗体-寡核苷酸缀合物和肽/蛋白质缀合物,对临床发展来说是更新的。这篇综述将评估基于蛋白质的化学缀合物的当前发展格局,特别注意诸如药代动力学的调节等考虑因素,安全性/耐受性,进入难以进入的目标,以及生物利用度。此外,为了这次审查的目的,所讨论的分子类型分为两类:(1)通过蛋白质或肽生物缀合增强的治疗剂,和(2)需要化学修饰的蛋白质和肽治疗剂。总的来说,每年新的基于肽或蛋白质的疗法在管道中流动的广度为追求更复杂的治疗策略提供了前进的道路。
    Over the past few decades, the complexity of molecular entities being advanced for therapeutic purposes has continued to evolve. A main propellent fueling innovation is the perpetual mandate within the pharmaceutical industry to meet the needs of novel disease areas and/or delivery challenges. As new mechanisms of action are uncovered, and as our understanding of existing mechanisms grows, the properties that are required and/or leveraged to enable therapeutic development continue to expand. One rapidly evolving area of interest is that of chemically enhanced peptide and protein therapeutics. While a variety of conjugate molecules such as antibody-drug conjugates, peptide/protein-PEG conjugates, and protein conjugate vaccines are already well established, others, such as antibody-oligonucleotide conjugates and peptide/protein conjugates using non-PEG polymers, are newer to clinical development. This review will evaluate the current development landscape of protein-based chemical conjugates with special attention to considerations such as modulation of pharmacokinetics, safety/tolerability, and entry into difficult to access targets, as well as bioavailability. Furthermore, for the purpose of this review, the types of molecules discussed are divided into two categories: (1) therapeutics that are enhanced by protein or peptide bioconjugation, and (2) protein and peptide therapeutics that require chemical modifications. Overall, the breadth of novel peptide- or protein-based therapeutics moving through the pipeline each year supports a path forward for the pursuit of even more complex therapeutic strategies.
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  • 文章类型: Journal Article
    纳米纤维素由于其生物相容性在生物医学领域具有巨大的潜力,大的比表面积,和可定制的表面化学。然而,由于生物惰性性质和机械强度的不匹配,纳米纤维素本身没有细胞粘附能力,不能直接促进细胞生长和繁殖。最近,纳米纤维素的表面功能化已被报道为改善其生物活性或其他物理化学性质的不可或缺的策略。在本文中,基于其固有羟基的纳米纤维素的功能化策略,醛,羧基,和硫酸基团反应进行了综述。生物大分子,如肽,蛋白质,总结了常用于功能化的不同生物医学应用的DNA。纳米纤维素基生物材料应用的前景和持续挑战,以及这些先进的加工技术,如增材制造,纳米制造,和生物制造也进行了讨论。这篇综述被认为是纳米纤维素基生物材料在生物医学应用中的发展指南。
    Nanocellulose has great potential in the biomedical field due to its biocompatibility, large specific surface area, and customizable surface chemistry. However, due to the bioinert nature and mismatch of the mechanical strength, nanocellulose itself has no cell adhesion ability and cannot directly promote cell growth and reproduction. Recently, surface functionalization of nanocellulose has been reported as an indispensable strategy for improving its bioactivities or other physic-chemical properties. In this paper, functionalization strategies of nanocellulose based on its inherent hydroxyl, aldehyde, carboxyl, and sulfate group reactions are reviewed. Biomacromolecules, such as peptides, proteins, and DNA that are commonly used in functionalization for different biomedical applications are summarized. Prospects and ongoing challenges of nanocellulose-based biomaterials application, as well as these advanced processing technologies such as additive manufacturing, nanomanufacturing, and bio-manufacturing are also discussed. This review is supposed to serve as a guideline for the development of nanocellulose-based biomaterials in biomedical applications.
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  • 文章类型: Journal Article
    变色龙标记(ChLs)在与生物分子的氨基结合时具有改变(可见)颜色和荧光的独特性质。MostChLs与脂族伯氨基反应,如赖氨酸中的那些,或与人工引入多聚核酸或糖类的氨基反应,但其他人也与仲氨基反应。在受控的情况下,反应相当具体。该评论细分为以下部分:(1)荧光标签的介绍和分类;(2)标记时发生短波颜色变化的吡喃合金标签,通常从蓝色到红色;(3)多甲基类型的标签(也经历短波颜色变化,通常从绿色到蓝色;(4)各种其他(不太常见的)显色和荧光系统;(5)在golongwavecoor变化下的半色素标记,通常从黄色到紫色;(6)ChLs在蛋白质和寡核苷酸标记中的应用;(7)在荧光测定和传感中的应用;(8)在生物分子荧光成像中的应用;(9)在亲和相互作用研究中的应用(受体-配体结合);(10)在表面和界面化学中的应用;(11)在色谱中的应用,生物分子的电泳和等速电泳。
    Chameleon labels (ChLs) possess the unique property of changing (visible) color and fluorescence on binding to amino groups of biomolecules. MostChLs react with primary aliphatic amino groups such as those in lysine or with amino groups artificially introduced into polynucleic acids or saccharides, but someothers also react with secondary amino groups. Under controlled circumstances, the reactions are fairly specific. The review is subdivided into the following sections: (1) An introduction and classification of fluorescent labels; (2) pyrylium labels that undergo shortwave color changes upon labelling, typically from blue to red; (3) polymethine type of labels (that also undergo shortwave color changes, typically from green to blue; (4) various other (less common) chromogenic and fluorogenic systems; (5) hemicyanine labels that undergolongwavecolor changes, typically from yellow to purple; (6) the application of ChLs to labeling of proteins and oligonucleotides; (7) applications to fluorometric assays and sensing; (8) applications to fluorescence imaging of biomolecules; (9) applications in studies on affinity interactions (receptor-ligand binding); (10) applications in surface and interface chemistry; and (11) applications in chromatography, electrophoresis and isotachophoresis of biomolecules.
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  • 文章类型: Journal Article
    Peptides exhibit unique binding behavior with graphene and its derivatives by forming bonds on its edges and planes. This makes them useful for sensing and imaging applications. This review with (155 refs.) summarizes the advances made in the last decade in the field of peptide-GO bioconjugation, and the use of these conjugates in analytical sciences and imaging. The introduction emphasizes the need for understanding the biotic-abiotic interactions in order to construct controllable peptide-functionalized graphitic material-based nanotools. The next section covers covalent and non-covalent interactions between peptide and oxidized graphene derivatives along with a discussion of the adsorption events during interfacing. We then describe applications of peptide-graphene conjugates in bioassays, with subsections on (a) detection of cancer cells, (b) monitoring protease activity, (c) determination of environmental pollutants and (d) determination of pathogenic microorganisms. The concluding section describes the current status of peptide functionalized graphitic bioconjugates and addresses future perspectives. Graphical abstractSchematic representation depicting biosensing applications of peptide functionalized graphene oxide.
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  • 文章类型: Journal Article
    This review (with 129 refs) summarizes the progress in electrochemical immunoassays combined with magnetic particles that was made in the past 5 years. The specifity of antibodies linked to electrochemical transduction (by amperometry, voltammetry, impedimetry or electrochemiluminescence) gains further attractive features by introducing magnetic nanoparticles (MNPs). This enables fairly easy preconcentration of analytes, minimizes matrix effects, and introduces an appropriate label. Following an introduction into the fundamentals of electrochemical immunoassays and on nanomaterials for respective uses, a large chapter addresses method for magnetic capture and preconcentration of analytes. A next chapter discusses commonly used labels such as dots, enzymes, metal and metal oxide nanoparticles and combined clusters. The large field of hybrid nanomaterials for use in such immunoassays is discussed next, with a focus on MNPs composites with various kinds of graphene variants, polydopamine, noble metal nanoparticles or nanotubes. Typical applications address clinical markers (mainly blood and urine parameters), diagnosis of cancer (markers and cells), detection of pathogens (with subsections on viruses and bacteria), and environmental and food contaminants as toxic agents and pesticides. A concluding section summarizes the present status, current challenges, and highlights future trends. Graphical abstract Magnetic nanoparticles (MNP) with antibodies (Ab) capture and preconcentrate analyte from sample (a) and afterwards become magnetically (b) or immunospecifically (c) bound at an electrode. Signal either increases due to the presence of alabel (b) or decreases as the redox probe is blocked (c).
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