纳米生物学——未来之挑战——中国科学院上海交叉学科研究中心第八次上海圆桌会议

纳米技术是科技部中长期规划基础研究重大专项之一,纳米生物学是其重要的一个分支。我们知道生物细胞已经成为研究纳米技术的重要场所。蛋白装配成纳米机器,它可以转化能量并制造出各种大分子。有些蛋白还可作为一种传感器行使功能。细胞其实就是由各种各样的分子器件组成,其中还有许多未知有待于我们去探索。目前,技术的发展还有赖于那些不可循环利用的资源,如石油、汽油、煤炭、金属等,在今后的几十年中,它们将逐步被取代。未来的工程师创造新技术时,     

单分子装置：传感器、连接器、致动器

生物大分子之所以可以实现生物学功能是与其独特的力学性质息息相关的。作为纳米科技领域一个重要工具,原子力显微镜（AFM）可以对纳米尺度的生物大分子进行操纵并检测其力学性质。本文介绍了利用原子力显微镜对几类特殊蛋白以及DNA的力学性质的研究结果,发现这些生物分子具有很好的力学传感、连接和致动能力,将来有望作为单分子装置在纳米世界发挥更多功用。     

封面故事

<正>在分子层面的生物学和医学研究中,需要将生物分子相互作用转换为可以探测的物理信号,以研究其过程、数量和机制。光学生物传感,即应用光学探针传感生物学信号,是应用最为广泛的一类。随着纳米生物技术的应用,光学生物传感探针的结构更加     

纳米生物催化的研究现状和发展态势

纳米生物催化领域包括:(ⅰ)利用纳米技术或纳米材料调控生物催化剂的效率;(ⅱ)直接利用纳米材料或技术实现生物催化功能,并拓展生物催化在非友好环境及疾病诊疗中的应用.纳米生物催化已成为纳米生物学重要的研究领域,主要涉及纳米载体固定化酶和纳米材料人工模拟酶(纳米酶).一方面,可以借助纳米技术或材料所具有的特殊纳米效应来增强生物催化剂的效率和稳定性.另一方面,从模拟酶的理念出发,借助纳米材料自身所具有的催化能力,直接实现对生化反应的催化,这类具有酶学特性的纳米酶被视为新一代人工模拟酶.近年来,基于纳米载体固定化酶和纳米酶技术的纳米生物催化已在疾病诊断和治疗、化工制药、环境处理等领域得到了广泛研究,并展示了其具有重要的应用价值.本文简要综述了纳米载体固定化酶和纳米酶的发展历程及应用进展.     

纳米颗粒与生物大分子的相互作用及其生物毒性机制

纳米颗粒已得到广泛的应用,同时其潜在的毒性及生物学效应也引起了广泛的关注。许多文献证实纳米颗粒对生物体具有毒性作用,但在分子水平上对其毒性机制的研究较少。本文对近年来纳米颗粒与生物大分子相互作用的最新研究进行了综述,包括纳米颗粒与蛋白质、脂类、核酸等生物分子间的相互作用。     

纳米生物学与纳米酶学：新兴交叉科学

纳米科学技术是20世纪80年代末期诞生并蓬勃发展的新兴科学技术,以多学科交叉融合为特色,为物理、化学、材料和生命科学等提供新的技术手段和研究视角.纳米材料的结构及表面物理化学性质直接决定了其与生物分子、细胞、组织、器官及个体的相互作用方式,并由此产生独特的生物效应——纳米生物效应.纳米生物学是从个体、细胞及分子水平深入研究纳米生物效应、阐明其精确机制的交叉科学,现已成为极具挑战性的热点前沿领域.中国科学家在纳米生物学领域已取得一系列令国际同行瞩目的重要进展,其中纳米酶(nanozyme)的开发及应用研究是极具代表性的原创发现之一.     

纳米医疗器械开发的巨大商机

日益发展的现代医疗设备已进入了分子和原子的水平 ,而且许多医疗设备也需要出乎想象之外的重新定义。纳米是十亿分之一米 ,大约是 3～ 5个原子的尺寸。纳米技术是操作分子和原子粒子来生产新的材料并加以处理使其具有所希望的特性 ,与传统的机构加工相反 ,使用纳米技术可以“从基底开始”一个一个原子、一个一个分子地来组装产品 ,它可以把制造工业改革得既简易又优良。2 0 0 2年 6月美国联邦机构纳米技术委员会认为与传统材料相比 ,纳米工程材料更轻、更强、更容易处理 ,且废品率更低 ,更便于开发和加工 ,美国国家科学基金会期望纳米技术…     

近场扫描光学成像结合量子点标记的纳米技术在细胞生物学中的应用

近场扫描光学显微镜（NSOM）对传统的光学分辨极限产生了革命性的突破,可在超高光学分辨率下无侵人性和无破坏性地对生物样品进行观测。量子点（QDs）具有极好的光学性能,如荧光寿命长、激发谱宽、生物相容性强、光稳定性好等优点,适合先进的生物成像。NSOM结合QDs标记的纳米技术被应用在细胞生物学中。通过纳米量级NSOM免疫荧光成像（50nm）对特定蛋白分子在细胞表面的动态分布进行可视化研究和数量化分析,阐明了蛋白分子在不同细胞过程中的作用机制。因此,NSOM／QD基成像系统提供了单个蛋白分子最高分辨率的荧光图像,为可视化研究蛋白分子机制的提供了一种强有力的工具。     

纳米材料在生物医学检测中的应用

纳米技术的兴起,对生物医学领域的变革产生了深远的影响。纳米材料是纳米技术发展的重要基础,它具有许多传统材料所不具备的独特的理化性质,因此在生物医学、传感器等重要技术领域有着广泛的应用前景。对几类常见的纳米材料包括纳米金、量子点、磁性纳米粒子、碳纳米管和硅纳米线在蛋白质、DNA、金属离子以及生物相关分子检测方面的应用进行综述。     

DNA折纸纳米载体在药物递送中的应用

DNA纳米技术是基于沃森克里克碱基配对原则产生可编程核酸结构的技术。因其具有高精度的工程设计、前所未有的可编程性和内在的生物相容性等特点，运用该技术合成的纳米结构不仅可以与小分子、核酸、蛋白质、病毒和癌细胞相互作用，还可以作为纳米载体，递送不同的治疗药物。DNA折纸作为一种有效的、多功能的方法来构建二维和三维可编程的纳米结构，是DNA纳米技术发展的一个里程碑。由于其高度可控的几何形状、空间寻址性、易于化学修饰，DNA折纸在许多领域具有巨大的应用潜力。本文通过介绍DNA折纸的起源、基本原理和目前进展，归纳总结了运用DNA折纸进行药物装载和释放的方式，并基于此技术，展望了今后的发展趋势以及所面临的机遇和挑战。     

Biophysics of single molecules

The modern methods of research on biological molecules which have led to the development of a new field of science, biophysics of single molecules, are reviewed. The measurement of the characteristics of single molecules enables one to reveal their individual features, and it is just for this reason that much more information can be obtained from one molecule than from the entire ensemble of molecules. The high sensitivity of the methods considered in detail makes it possible to come close to solving the basic problem of practical importance, namely, the determination of the nucleotide sequence of a single DNA molecule.     

Thermal stability and conformation of DNA and proteins under the confined condition in the matrix of hydrogels

Spatially confined environments are seen in biological systems and in the fields of biotechnology and nanotechnology. The confinement restricts the conformational space of polymeric molecules and increasing the degree of molecular crowding. Here, we developed preparation methods for agarose and polyacrylamide gels applicable to UV spectroscopy that can evaluate the confinement effects on DNA and protein structures. Measurements of UV absorbance and CD spectra showed no significant effect of the confinement in the porous media of agarose gels on the base-pair stability of DNA polynucleotides [poly(dA)/poly(dT)] and oligonucleotides (hairpin, duplex, and triplex structures). On the other hand, a highly confined environment created by polyacrylamide gels at high concentrations increased the stability of polynucleotides while leaving that of oligonucleotides unaffected. The changes in the base-pair stability of the polynucleotides were accompanied by the perturbation of the helical conformation. The polyacrylamide gels prepared in this study were also used for the studies on proteins (lysozyme, bovine serum albumin, and myoglobin). The effects on the proteins were different from the effects on DNA structures, suggesting different nature of interactions within the gel. The experimental methods and results are useful to understand the physical properties of nucleic acids and proteins under confined conditions.     

Synthesis,characterization, and antibacterial properties of silver nanoparticles-graphene and graphene oxide composites

In the field of nanotechnology, silver nanoparticles have been considered a promising antibacterial material for a century. The potential applications of graphene-based materials are increasingly recognized for their special physico-chemical and biological properties. In particular, graphene and graphene oxide as the foundation of nanocomposites have garnered much interest among researchers in many fields. In this review, we concentrate on different aspects of silver nanoparticle composites with graphene and graphene oxide, focusing on their synthesis methods, special characteristics, and antibacterial properties; we also briefly discuss limitations and future research.     

Possible implications in the use of exogenous phospholipids.

The development of new techniques has shed more light on the physical state of phospholipids within the living cell. This has helped in the development of new concepts of the structural inter-relationship of phospholipids with proteins and other natural constituents and also of their functional role (e.g. enzyme modulators). On the other hand, understanding of phospholipid behaviour within the biological environment has encouraged research into the possibility of assigning to these molecules the role of carriers for exogenous or endogenous biologically active agents. Possible applications of this carrier potential in biology and medicine are discussed.     

Lessons learned from protein aggregation: toward technological and biomedical applications

The close relationship between protein aggregation and neurodegenerative diseases has been the driving force behind the renewed interest in a field where biophysics, neurobiology and nanotechnology converge in the study of the aggregate state. On one hand, knowledge of the molecular principles that govern the processes of protein aggregation has a direct impact on the design of new drugs for high-incidence pathologies that currently can only be treated palliatively. On the other hand, exploiting the benefits of protein aggregation in the design of new nanomaterials could have a strong impact on biotechnology. Here we review the contributions of our research group on novel neuroprotective strategies developed using a purely biophysical approach. First, we examine how doxycycline, a well-known and innocuous antibiotic, can reshape α-synuclein oligomers into non-toxic high-molecular-weight species with decreased ability to destabilize biological membranes, affect cell viability and form additional toxic species. This mechanism can be exploited to diminish the toxicity of α-synuclein oligomers in Parkinson’s disease. Second, we discuss a novel function in proteostasis for extracellular glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in combination with a specific glycosaminoglycan (GAG) present in the extracellular matrix. GAPDH, by changing its quaternary structure from a tetramer to protofibrillar assembly, can kidnap toxic species of α-synuclein, and thereby interfere with the spreading of the disease. Finally, we review a brighter side of protein aggregation, that of exploiting the physicochemical advantages of amyloid aggregates as nanomaterials. For this, we designed a new generation of insoluble biocatalysts based on the binding of photo-immobilized enzymes onto hybrid protein:GAG amyloid nanofibrils. These new nanomaterials can be easily functionalized by attaching different enzymes through dityrosine covalent bonds.     

Origins of life: a route to nanotechnology.

The origins of life and nanotechnology are two seemingly disparate areas of scientific investigation. However, the fundamental questions of life's beginnings and the applied construction of a Drexlerian nanotechnology both share a similar problem; how did and how can self-reproducing molecular machines originate? Here we draw attention to the coincidence between nanotechnology and origins research with particular attention paid to the spontaneous adsorption and scanning tunneling microscopy investigation of purine and pyrimidine bases self-organized into monolayers, adsorbed to the surfaces of crystalline solids. These molecules which encode biological information in nucleic acids, can form supramolecular architectures exhibiting enantiomorphism with the complexity to store and encode putative protobiological information. We conclude that the application of nanotechnology to the investigation of life's origins, and vice versa, could provide a viable route to an evolution-driven synthetic life.     

Metallic nanoparticles: microbial synthesis and unique properties for biotechnological applications,bioavailability and biotransformation

The impact of nanotechnology in all areas of science and technology is evident. The expanding availability of a variety of nanostructures with properties in the nanometer size range has sparked widespread interest in their use in biotechnological systems, including the field of environmental remediation. Nanomaterials can be used as catalysts, adsorbents, membranes, water disinfectants and additives to increase catalytic activity and capability due to their high specific surface areas and nanosize effects. Thus, nanomaterials appear promising for new effective environmental technologies. Definitely, nanotechnology applications for site remediation and wastewater treatment are currently in research and development stages, and new innovations are underway. The synthesis of metallic nanoparticles has been intensively developed not only due to its fundamental scientific interest but also for many technological applications. The use of microorganisms in the synthesis of nanoparticles is a relatively new eco-friendly and promising area of research with considerable potential for expansion. On the other hand, chemical synthesis occurs generally under extreme conditions (e.g. pH, temperature) and also chemicals used may have associated environmental and human health impacts. This review is an overview of current research worldwide on the use of microorganisms during the biosynthesis of metallic nanoparticles and their unique properties that make them good candidates for many applications, including in biotechnology.     

Recent trends in non-viral vector-mediated gene delivery

Nucleic acids-based next generation biopharmaceuticals (i.e., pDNA, oligonucleotides, short interfering RNA) are potential pioneering materials to cope with various incurable diseases. However, several biological barriers present a challenge for efficient gene delivery. On the other hand, developments in nanotechnology now offer numerous non-viral vectors that have been fabricated and found capable of transmitting the biopharmaceuticals into the cell and even into specific subcellular compartments like mitochondria. This overview illustrates cellular barriers and current status of non-viral gene vectors, i.e., lipoplexes, liposomes, polyplexes, and nanoparticles, to relocate therapeutic DNA-based nanomedicine into the target cell. Despite the awesome impact of physical methods (i.e., ultrasound, electroporation), chemical methods have been shown to accomplish high-level and safe transgene expression. Further comprehension of barriers and the mechanism of cellular uptake will facilitate development of nucleic acids-based nanotherapy for alleviation of various disorders.     

A Lipidomic Study of the Effects of N-methyl-N′-nitro-N-nitrosoguanidine on Sphingomyelin Metabolism

Systems biology is a new and rapidly developing research area in which,by quantitativelydescribing the interaction among all the individual components of a cell,a systems-level understanding of abiological response can be achieved.Therefore,it requires high-throughput measurement technologies forbiological molecules,such as genomic and proteomic approaches for DNA/RNA and protein,respectively.Recently,a new concept,lipidomics,which utilizes the mass spectrometry(MS)method for lipid analysis,has been proposed.Using this lipidomic approach,the effects of N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)on sphingomyelin metabolism,a major class of sphingolipids,were evaluated.Sphingomyelin moleculeswere extracted from cells and analyzed by matrix-assisted laser desorption ionization-time of flight MS.Itwas found that MNNG induced profound changes in sphingomyelin metabolism,including the appearance ofsome new sphingomyelin species and the disappearance of some others,and the concentrations of severalsphmgomyelin species also changed.This was accompanied by the redistribution of acid sphingomyelinase(ASM),a key player in sphingomyelin metabolism.On the other hand,imipramine,an inhibitor of ASM,caused the accumulation of sphingomyelin.It also prevented some of the effects of MNNG,as well as theredistribution of ASM.Taken together,these data suggested that the lipidomic approach is highly effectivefor the systematic analysis of cellular lipids metabolism.     

Nanotechnology based anti‐infectives to fight microbial intrusions

With the rise in human population across the globe especially in developing countries, the incidence of microbial infections are increasing with greater pace. On the other hand, available medication and therapies are found to be insufficient for the complete cure of such microbial infections due to the development of resistance against various antibiotics. Therefore, to cope up the menace of microbial infections and drug resistance, there is demand for new and compelling technology, which has the ability to impede these problems. Many research groups worldwide are finding a ray of hope in nanomaterials owing to their unique properties. In the present review we have discussed the reasons behind the development of new materials based on nanotechnology. It is mainly focused on pioneering studies on application of nanomaterials like carbon nanotube, fullerene, dendrimers, nanocomposite and metal nanoparticles in combating dreadful pathogens. Moreover, the concerns about their toxicity have also been discussed.