金属有机框架纳米酶的研究进展

纳米酶作为一种具有类酶活性的纳米材料,与天然酶相比,具有制备过程简单、受外界环境干扰小、对酸碱和温度具有较好的耐受性等优点.金属有机框架(metal-organic frameworks,MOFs),即多孔配位聚合物,具有结构多样性、高比表面积、孔隙率可控等独特性质.因有序框架的保护以及结构可调控的性质,基于MOFs构建的纳米酶受到研究人员的广泛关注.本文综述不同类型MOFs基的纳米酶,主要从原始MOFs、化学修饰的MOFs、MOFs基复合材料和MOFs衍生物等四大方面进行论述;随后,对4种类型MOFs基纳米酶的构建特点和生化分析应用进行归纳和比较;最后对其当前面临的挑战和未来的发展趋势进行讨论.     

Biomolecule-embedded metal-organic frameworks as an innovative sensing platform

Technological advancements combined with materials research have led to the generation of enormous types of novel substrates and materials for use in various biological/medical, energy, and environmental applications. Lately, the embedding of biomolecules in novel and/or advanced materials (e.g., metal-organic frameworks (MOFs), nanoparticles, hydrogels, graphene, and their hybrid composites) has become a vital research area in the construction of an innovative platform for various applications including sensors (or biosensors), biofuel cells, and bioelectronic devices. Due to the intriguing properties of MOFs (e.g., framework architecture, topology, and optical properties), they have contributed considerably to recent progresses in enzymatic catalysis, antibody-antigen interactions, or many other related approaches. Here, we aim to describe the different strategies for the design and synthesis of diverse biomolecule-embedded MOFs for various sensing (e.g., optical, electrochemical, biological, and miscellaneous) techniques. Additionally, the benefits and future prospective of MOFs-based biomolecular immobilization as an innovative sensing platform are discussed along with the evaluation on their performance to seek for further development in this emerging research area.     

基于金属有机骨架的生物复合物抗逆性研究进展

金属有机骨架 (Metal-organic frameworks,MOFs) 由金属离子/簇和有机配体通过自组装形成,在催化、传感、能源和生物医药等领域有十分广泛的应用。近年来,金属有机骨架和生物活性物质结合引起了许多研究者的关注。金属有机骨架具有超大孔容、高比表面积、多样性结构组成等优势,使其可作为固定载体保护生物活性物质免受外界不良微环境的影响,包括高温、高压、有机溶剂等,从而提高生物活性物质的抗逆性。文中从金属有机骨架作为保护层提高不同种类生物活性物质抗逆性的角度进行了综述,并贯穿介绍了基于金属有机骨架的生物复合物的合成策略,旨在为相关领域的研究人员提供参考,促进基于金属有机骨架的生物复合物的实际应用。     

DNA水凝胶的制备及应用

脱氧核糖核酸(Deoxyribonucleic acid,DNA)不仅可作为生物遗传的物质基础,又以其可编程性、功能多样性、生物相容性和生物可降解性等优点,在生物材料的构建方面表现出巨大的潜力。DNA水凝胶是一种主要由DNA参与形成的三维网状聚合物材料,同时因其保留的DNA生物性能与自身骨架的机械性能的完美融合使得它成为近年来最受关注的新兴功能高分子材料之一。目前,基于各种功能核酸序列或通过结合不同的功能材料制备的单组分或多组分DNA水凝胶,已广泛用于生物医学、分子检测及环境保护的研究或应用领域中。文中主要总结了近十几年来DNA水凝胶制备方法上的研究进展,探讨了DNA水凝胶的分类策略,并进一步综述了DNA水凝胶在药物运输、生物传感、细胞培养等方面的应用研究。最后对DNA水凝胶未来的发展方向以及可能面临的挑战进行了展望。     

多级孔金属-有机框架固定化酶的研究进展

金属-有机框架(metal-organic frameworks, MOFs)作为酶固定化的优良载体,为生物催化反应提供优越的物理和化学保护。近年来,多级孔金属-有机框架(hierarchical porous metal-organic frameworks, HP-MOFs)由于其独特的结构优势,在固定化酶方面显示出更大的潜力。到目前为止,已经开发了各类具有原生多级孔或缺陷多级孔的HP-MOFs用于酶的固定化研究,并且使得固定化酶在催化活性、稳定性和重复利用性等方面得到了显著增强。本文系统总结了HP-MOFs用于固定化酶的各种策略,介绍了HP-MOFs固定化酶(enzyme@HP-MOFs)在催化合成、生物传感、生物医药等领域的最新应用进展。最后,讨论并展望了HP-MOFs固定化酶这一领域所面临的挑战和机遇。     

卟啉金属有机骨架材料在肿瘤治疗中的应用

目前,恶性肿瘤严重威胁人类健康和生命。临床上常用放疗法和化疗法治疗肿瘤,在一定程度上抑制肿瘤的生长和转移。但是,传统的化疗药物在给药过程中缺乏靶向性、副作用大,而且大多数化疗药物水溶性差,效果有限,高剂量的重复给药会导致耐药,单一模式的治疗策略效果不佳。因此通过构建靶向智能多功能纳米载药系统实现肿瘤精准诊断和治疗成为近年来的研究热点。卟啉金属有机骨架（MOFs）材料具有多孔性、大比表面积、表面可修饰等特性,有望成为良好的靶向刺激响应型药物载体。而且卟啉MOFs可以避免卟啉分子的自聚集以及在激发态的自猝灭,还具有卟啉分子的宽光谱响应范围,是一类具有广阔应用前景的固体光敏剂,因此卟啉MOFs近年来成为构建靶向智能多功能纳米载药系统的重要平台。本论文综述了近年来基于卟啉金属有机骨架材料的肿瘤治疗策略,特别是基于肿瘤内源性组分（pH、酶、氧化还原）和外源性物理信号（声、磁、光）刺激触发的多功能纳米平台用于肿瘤精准诊断和治疗的最新研究进展,并讨论了卟啉MOFs在未来肿瘤治疗中面临的挑战和机遇。     

DNA framework-engineered electrochemical biosensors

Self-assembled DNA nanostructures have shown remarkable potential in the engineering of biosensing interfaces, which can improve the performance of various biosensors. In particular, by exploiting the structural rigidity and programmability of the framework nucleic acids with high precision, molecular recognition on the electrochemical biosensing interface has been significantly enhanced, leading to the development of highly sensitive and specific biosensors for nucleic acids, small molecules,proteins, and cells. In this review, we summarize recent advances in DNA framework-engineered biosensing interfaces and the application of corresponding electrochemical biosensors.     

Luminescence nanomaterials for biosensing applications

Due to their capacity to immobilize more bioreceptor parts at reduced volumes, nanomaterials have emerged as potential tools for increasing the sensitivity to specific molecules. Furthermore, carbon nanotubes, gold nanoparticles, polymer nanoparticles, semiconductor quantum dots, nanodiamonds, and graphene are among the nanomaterials that are under investigation. Due to the fast development of this field of research, this review summarizes the classification of biosensors using the main receptors and design of biosensors. Numerous studies have concentrated on the manipulation of persistent luminescence nanoparticles (PLNPs) in biosensing, cell tracking, bioimaging, and cancer therapy due to the effective removal of autofluorescence interference from tissues and the ultra-long near-infrared afterglow emission. As luminescence has a unique optical property, it can be detected without constant external illumination, preventing autofluorescence and light dispersion through tissues. These successes have sparked an increasing interest in creating novel PLNP types with the desired superior properties and multiple applications. In this review, we emphasize the most recent developments in biosensing, imaging, and image-guided therapy whilst summarizing the research on synthesis methods, bioapplications, biomembrane modification, and the biosafety of PLNPs. Finally, the remaining issues and difficulties are examined together with prospective future developments in the biomedical application field.     

Metal–Organic Framework Composites for Theragnostics and Drug Delivery Applications

Among a plethora of nano-sized therapeutics, metal-organic frameworks (MOFs) have been some of the most investigated novel materials for, predominantly, cancer drug delivery applications. Due to their large drug uptake capacities and slow-release mechanisms, MOFs are desirable drug delivery vehicles that protect and transport sensitive drug molecules to target sites. The inclusion of other guest materials into MOFs to make MOF-composite materials has added further functionality, from externally triggered drug release to improved pharmacokinetics and diagnostic aids. MOF-composites are synthetically versatile and can include examples such as magnetic nanoparticles in MOFs for MRI image contrast and polymer coatings that improve the blood-circulation time. From synthesis to applications, this review will consider the main developments in MOF-composite chemistry for biomedical applications and demonstrate the potential of these novel agents in nanomedicine. It is concluded that, although vast synthetic progress has been made in the field, it requires now to develop more biomedical expertise with a focus on rational model selection, a major comparative toxicity study, and advanced targeting techniques.     

Recent progresses in biomedical applications of aptamer-functionalized systems

Aptamers, known as “chemical antibodies” are screened via a combinational technology of systematic evolution of ligands by exponential enrichment (SELEX). Due to their specific targeting ability, high binding affinity, low immunogenicity and easy modification, aptamer-functionalized systems have been extensively applied in various fields and exhibit favorable results. However, there is still a long way for them to be commercialized, and few aptamer-functionalized systems have yet successfully entered clinical and industrial use. Thus, it is necessary to overview the recent research progresses of aptamer-functionalized systems for the researchers to improve or design novel and better aptamer-functionalized systems. In this review, we first introduce the recent progresses of aptamer-functionalized systems’ applications in biosensing, targeted drug delivery, gene therapy and cancer cell imaging, followed by a discussion of the challenges faced with extensive applications of aptamer-functionalized systems and speculation of the future prospects of them.     

Peptide self-assembly at the nanoscale: a challenging target for computational and experimental biotechnology

Self-assembly at the nanoscale is becoming increasingly important for the fabrication of novel supramolecular structures, with applications in the fields of nanobiotechnology and nanomedicine. Peptides represent the most favorable building blocks for the design and synthesis of nanostructures because they offer a great diversity of chemical and physical properties, they can be synthesized in large amounts, and can be modified and decorated with functional elements, which can be used in diverse applications. In this article, we review some of the most recent experimental advances in the use of nanoscale self-assembled peptide structures and the theoretical efforts aimed at understanding the microscopic determinants of their formation, stability and conformational properties. The combination of experimental observations and theoretical advances will be fundamental to fully realizing the biotechnological potential of peptide self-organization.     

Outer membrane vesicles (OMVs) enabled bio-applications: A critical review

Outer membrane vesicles (OMVs) are nanoscale spherical vesicles released from Gram-negative bacteria. The lipid bilayer membrane structure of OMVs consists of similar components as bacterial membrane and thus has attracted more and more attention in exploiting OMVs' bio-applications. Although the endotoxic lipopolysaccharide on natural OMVs may impose potential limits on their clinical applications, genetic modification can reduce their endotoxicity and decorate OMVs with multiple functional proteins. These genetically engineered OMVs have been employed in various fields including vaccination, drug delivery, cancer therapy, bioimaging, biosensing, and enzyme carrier. This review will first briefly introduce the background of OMVs followed by recent advances in functionalization and various applications of engineered OMVs with an emphasis on the working principles and their performance, and then discuss about the future trends of OMVs in biomedical applications.     

Metal‐Organic Frameworks for Carbon Dioxide Capture and Methane Storage

In the global transition to a sustainable low‐carbon economy, CO₂ capture and storage technology still plays a critical role for deep emission reduction, particularly for the stationary sources in power generation and industry. However, for small and mobile emission sources in transportation, CO₂ capture is not suitable and it is more practical to use relatively clean energy, such as natural gas. In these two low‐carbon energy technologies, designing highly selective sorbents is one of the key and most challenging steps. Toward this end, metal‐organic frameworks (MOFs) have received continuously intensive attention in the past decades for their highly porous and diversified structures. In this review, the recent progress in developing MOFs for selective CO₂ capture from post‐combustion flue gas and CH₄ storage for vehicle applications are summarized. For CO₂ capture, several promising strategies being used to improve CO₂ adsorption uptake at low pressures are highlighted and compared. In addition, the conventional and novel regeneration techniques for MOFs are also discussed. In the case of CH₄ storage, the flexible and rigid MOFs, whose CH₄ storage capacity is close to the target set by U.S. Department of Energy are particularly emphasized. Finally, the challenge of using MOFs for CH₄ storage is discussed.     

Nucleic acid approaches for detection and identification of biological warfare and infectious disease agents

Biological warfare agents are the most problematic of the weapons of mass destruction and terror. Both civilian and military sources predict that over the next decade the threat from proliferation of these agents will increase significantly. In this review we summarize the state of the art in detection and identification of biological threat agents based on PCR technology with emphasis on the new technology of microarrays. The advantages and limitations of real-time PCR technology and a review of the literature as it applies to pathogen and virus detection are presented. The paper covers a number of issues related to the challenges facing biological threat agent detection technologies and identifies critical components that must be overcome for the emergence of reliable PCR-based DNA technologies as bioterrorism countermeasures and for environmental applications. The review evaluates various system components developed for an integrated DNA microchip and the potential applications of the next generation of fully automated DNA analyzers with integrated sample preparation and biosensing elements. The article also reviews promising devices and technologies that are near to being, or have been, commercialized.     

Gold nanoparticle-based signal amplification for biosensing

Colloidal gold nanoparticles (AuNPs), with unique properties such as highly resonant particle plasmons, direct visualization of single nanoclusters by scattering of light, catalytic size enhancement by silver deposition, conductivity, and electrochemical properties, are very attractive materials for several applications in biotechnology. Furthermore, as excellent biological tags, AuNPs can be easily conjugated with biomolecules and retain the biochemical activity of the tagged biomolecules, making AuNPs ideal transducers for several biorecognition applications. The goal of this article is to review recent advances of using AuNPs as labels for signal amplification in biosensing applications. We focus on the signal amplification strategies of AuNPs in biosensing/biorecognition, more specifically, on the main optical and electrochemical detection methods that involve AuNP-based biosensing. Particular attention is given to recent advances and trends in sensing applications.     

The current state of the art of quantitative phosphoproteomics and its applications to diabetes research

Protein phosphorylation is a fundamental regulatory mechanism in many cellular processes and aberrant perturbation of phosphorylation has been implicated in various human diseases. Kinases and their cognate inhibitors have been considered as hotspots for drug development. Therefore, the emerging tools, which enable a system-wide quantitative profiling of phosphoproteome, would offer a powerful impetus in unveiling novel signaling pathways, drug targets and/or biomarkers for diseases of interest. This review highlights recent advances in phosphoproteomics, the current state of the art of the technologies and the challenges and future perspectives of this research area. Finally, some exemplary applications of phosphoproteomics in diabetes research are underscored.     

Therapeutic synthetic gene networks

The field of synthetic biology is rapidly expanding and has over the past years evolved from the development of simple gene networks to complex treatment-oriented circuits. The reprogramming of cell fate with open-loop or closed-loop synthetic control circuits along with biologically implemented logical functions have fostered applications spanning over a wide range of disciplines, including artificial insemination, personalized medicine and the treatment of cancer and metabolic disorders. In this review we describe several applications of interactive gene networks, a synthetic biology-based approach for future gene therapy, as well as the utilization of synthetic gene circuits as blueprints for the design of stimuli-responsive biohybrid materials. The recent progress in synthetic biology, including the rewiring of biosensing devices with the body's endogenous network as well as novel therapeutic approaches originating from interdisciplinary work, generates numerous opportunities for future biomedical applications.     

Microbial biosensors: a review

A microbial biosensor is an analytical device which integrates microorganism(s) with a physical transducer to generate a measurable signal proportional to the concentration of analytes. In recent years, a large number of microbial biosensors have been developed for environmental, food, and biomedical applications. Starting with the discussion of various sensing techniques commonly used in microbial biosensing, this review article concentrates on the summarization of the recent progress in the fabrication and application of microbial biosensors based on amperometry, potentiometry, conductometry, voltammetry, microbial fuel cell, fluorescence, bioluminescence, and colorimetry, respectively. Prospective strategies for the design of future microbial biosensors will also be discussed.     

Fluorescent labels in biosensors for pathogen detection

Infectious diseases caused by pathogens have become a life-threatening problem for millions of people around the world in recent years. Therefore, the need of efficient, fast, low-cost and user-friendly biosensing systems to monitor pathogen has increased enormously in the last few years. This paper presents an overview of different fluorescent labels and the utilization of fluorescence-based biosensor techniques for rapid, direct, sensitive and real-time identification of bacteria. In these biosensors, organic dyes, nanomaterials and rare-earth elements are playing an increasing role in the design of biosensing systems with an interest for applications in bacterial analysis.     

Single Domain Antibodies as a Powerful Tool for High Quality Surface Plasmon Resonance Studies

Single domain antibodies are recombinantly expressed functional antibodies devoid of light chains. These binding elements are derived from heavy chain antibodies found in camelids and offer several distinctive properties for applications in biotechnology such as small size, stability, solubility, and expression in high yields. In this study we demonstrated the potential of using single domain antibodies as capturing molecules in biosensing applications. Single domain antibodies raised against green fluorescent protein were anchored onto biosensor surfaces by using several immobilization strategies based on Ni²⁺:nitrilotriacetic acid-polyhistidine tag, antibody-antigen, biotin-streptavidin interactions and amine-coupling chemistry. The interaction with the specific target of the single domain antibodies was characterized by surface plasmon resonance. The immobilized single domain antibodies show high affinities for their antigens with K_D = 3–6 nM and outperform other antibody partners as capturing molecules facilitating also the data analysis. Furthermore they offer high resistance and stability to a wide range of denaturing agents. These unique biophysical properties and the production of novel single domain antibodies against affinity tags make them particularly attractive for use in biosensing and diagnostic assays.