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DNA three-way junctions are critical in various biological processes and hold significant potential for disease treatment and therapeutic applications. In this study, it is demonstrated that triple-stranded dinuclear [Ni 2 L 3 ] 4+ cylinders (L = C 25 H 20 N 4 ) exhibit a preferential binding affinity for Y-shaped DNA three-way junctions (3WJs), even in the presence of an excess of competing DNA structures, including G-quadruplexes. Notably, the investigated Ni(II) cylinders are capable of halting DNA synthesis catalyzed by DNA polymerase by stabilizing the 3WJ on the template strand. Using an extended 1D nanoarchitecture model, it is further established the high affinity and selectivity of the cylinders for DNA 3WJs and explored their potential application in stabilizing short-armed 3WJs for constructing DNA nanomaterials. The combined use of Ni(II) cylinders and DNA damage response inhibitors also revealed that the cylinders promote DNA damage, leading to the formation of double-strand breaks. This effect is likely associated with i) the binding of cylinders to 3WJs and ii) the cytotoxic activity of the cylinders in cancer cells., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Sensitive and quantitative detection of chemical and biological molecules for screening, diagnosis and monitoring diseases is essential to treatment planning and response monitoring. Electrochemical biosensors are fast, sensitive, and easy to miniaturize, which has led to rapid development in clinical diagnosis. Benefiting from their excellent molecular recognition ability and high programmability, DNA nanomaterials could overcome the Debye length of electrochemical biosensors by simple molecular design and are well suited as recognition elements for electrochemical biosensors. Therefore, to enhance the sensitivity and specificity of electrochemical biosensors, significant progress has been made in recent years by optimizing the DNA nanomaterials design. Here, the establishment of electrochemical sensing strategies based on DNA nanomaterials is reviewed in detail. First, the structural design of DNA nanomaterial is examined to enhance the sensitivity of electrochemical biosensors by improving recognition and overcoming Debye length. In addition, the strategies of electrical signal transduction and signal amplification based on DNA nanomaterials are reviewed, and the applications of DNA nanomaterial-based electrochemical biosensors and integrated devices in clinical diagnosis are further summarized. Finally, the main opportunities and challenges of DNA nanomaterial-based electrochemical biosensors in detecting disease biomarkers are presented in an aim to guide the design of DNA nanomaterial-based electrochemical devices with high sensitivity and specificity.

Extracellular vesicles (EVs) are cell-secreted biological nanoparticles that are critical mediators of intercellular communication. They contain diverse bioactive components, which are promising diagnostic biomarkers and therapeutic agents. Their nanosized membrane-bound structures and innate ability to transport functional cargo across major biological barriers make them promising candidates as drug delivery vehicles. However, the complex biology and heterogeneity of EVs pose significant challenges for their controlled and actionable applications in diagnostics and therapeutics. Recently, DNA molecules with high biocompatibility emerge as excellent functional blocks for surface engineering of EVs. The robust Watson-Crick base pairing of DNA molecules and the resulting programmable DNA nanomaterials provide the EV surface with precise structural customization and adjustable physical and chemical properties, creating unprecedented opportunities for EV biomedical applications. This review focuses on the recent advances in the utilization of programmable DNA to engineer EV surfaces. The biology, function, and biomedical applications of EVs are summarized and the state-of-the-art achievements in EV isolation, analysis, and delivery based on DNA nanomaterials are introduced. Finally, the challenges and new frontiers in EV engineering are discussed., (© 2023 Wiley‐VCH GmbH.)

DNA nanomaterials have been widely employed for various biomedical applications. With rapid development of chemical modification of nucleic acid, serials of stimuli-responsive elements are included in the multifunctional DNA nanomaterials. In this review, we summarize the recent advances in light responsive DNA nanomaterials based on photocleavage/photodecage, photoisomerization, and photocrosslinking for efficient bioimaging (including imaging of small molecule, microRNA, and protein) and drug delivery (including delivery of small molecule, nucleic acid, and gene editing system). We also discuss the remaining challenges and future perspectives of the light responsive DNA nanomaterials in biomedical applications., (© 2024 Wiley-VCH GmbH.)

Extracellular vesicles (EVs) are cell-derived nanovesicles comprising a myriad of molecular cargo such as proteins and nucleic acids, playing essential roles in intercellular communication and physiological and pathological processes. EVs have received substantial attention as noninvasive biomarkers for disease diagnosis and prognosis. Owing to their ability to recognize protein and nucleic acid targets, DNA-based nanomaterials with excellent programmability and modifiability provide a promising tool for the sensitive and accurate detection of molecular cargo carried by EVs. In this perspective, recent advancements in EV analysis using a variety of DNA-based nanomaterials are summarized, which can be broadly classified into three categories: linear DNA probes, DNA nanostructures, and hybrid DNA nanomaterials. The design, construction, advantages, and disadvantages of different types of DNA nanomaterials, as well as their performance for detecting EVs are reviewed. The challenges and opportunities in the field of EV analysis by DNA nanomaterials are also discussed., (© 2023 Wiley‐VCH GmbH.)

DNA can be used for precise construction of complex and flexible micro-nanostructures, including DNA origami, frame nucleic acids, and DNA hydrogels. DNA nanomaterials have good biocompatibility and can enter macrophages via scavenger receptor-mediated endocytosis. DNA nanomaterials can be uniquely and flexibly designed to ensure efficient uptake by macrophages, which represents a novel strategy to regulate macrophage function. With the development of nanotechnology, major advances have been made in the design and manufacturing of DNA nanomaterials for clinical therapy. In diseases accompanied by macrophage disturbances including tumor, infectious diseases, arthritis, fibrosis, acute lung injury, and atherosclerosis, DNA nanomaterials received considerable attention as potential treatments. However, we lack sufficient information to guarantee precise targeting of macrophages by DNA nanomaterials, which precludes their therapeutic applications. In this review, we summarize recent studies of macrophage-targeting DNA nanomaterials and discuss the limitations and challenges of this approach with regard to its potential use as a biological therapy., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Tu et al.)

DNA nanomaterials have been widely employed for various biomedical applications. With rapid development of chemical modification of nucleic acid, serials of stimuli‐responsive elements are included in the multifunctional DNA nanomaterials. In this review, we summarize the recent advances in light responsive DNA nanomaterials based on photocleavage/photodecage, photoisomerization, and photocrosslinking for efficient bioimaging (including imaging of small molecule, microRNA, and protein) and drug delivery (including delivery of small molecule, nucleic acid, and gene editing system). We also discuss the remaining challenges and future perspectives of the light responsive DNA nanomaterials in biomedical applications. [ABSTRACT FROM AUTHOR]

DNA nanoparticles hold great promise for a range of biological applications, including the development of cutting-edge treatments and diagnostic tests. Their subnanometer-level addressability enables precise, specific modifications with a variety of chemical and biological entities, making them ideal as diagnostic instruments and carriers for targeted delivery. This paper focuses on the potential of DNA nanomaterials, which offer scalability, programmability, and functionality. For example, they can be engineered to provide highly specific biosensing and bioimaging capabilities and show promise as a platform for disease diagnosis and treatment. Successful operation of various biomedical nanomaterials has been demonstrated both in vitro and in vivo. However, there are still significant challenges to overcome, including the need to improve the scalability and reliability of the technology, and to ensure safety in clinical applications. We discuss these challenges and opportunities in detail and highlight the progress and prospects of DNA nanotechnology for biomedical applications. [ABSTRACT FROM AUTHOR]

Food safety has always been a major global challenge to human health and the effective detection of harmful substances in food can reduce the risk to human health. However, the food industry has been plagued by a lack of effective and sensitive safety monitoring methods due to the tension between the cost and effectiveness of monitoring. DNA-based hydrogels combine the advantages of biocompatibility, programmability, the molecular recognition of DNA molecules, and the hydrophilicity of hydrogels, making them a hotspot in the research field of new nanomaterials. The stimulus response property greatly broadens the function and application range of DNA hydrogel. In recent years, DNA hydrogels based on stimulus-responsive mechanisms have been widely applied in the field of biosensing for the detection of a variety of target substances, including various food contaminants. In this review, we describe the recent advances in the preparation of stimuli-responsive DNA hydrogels, highlighting the progress of its application in food safety detection. Finally, we also discuss the challenges and future application of stimulus-responsive DNA hydrogels. [ABSTRACT FROM AUTHOR]

We have fabricated a DNA-based nanofiber created by self-assembly of guanine quadruplex (Hoogsteen base pairing) and double-stranded DNA (Watson-Crick base pairing). When duplexes containing a long stretch of contiguous guanines and single-stranded overhangs are incubated in potassium-containing buffer, the preformed duplexes create high molecular weight species that contain quadruplexes. In addition to observation of these larger species by gel electrophoresis, solutions were analyzed by atomic force microscopy to reveal nanofibers. Analysis of the atomic force microscopy images indicates that fibers form with lengths ranging from 250 to 2,000 nm and heights from 0.45 to 4.0 nm. This work is a first step toward the creation of new structurally heterogeneous (quadruplex/duplex), yet controllable, DNA-based materials exhibiting novel properties suitable for a diverse array of nanotechnology applications [ABSTRACT FROM AUTHOR]

Summary: Freestanding ultrathin nano-membranes (FUN-membranes) are two-dimensional materials of nanoscale thickness (less than 100nm) with little or no substrate support. Recently, there has been an emerging interest to rationally design such membranes for a broad spectrum of appealing applications ranging from lightweight, foldable electronic devices to highly efficient separation and sensing systems. In this review, we aim to summarize the recent developments of FUN-membranes fabricated via an assortment of bottom-up self-assembly strategies. In particular, we will describe the various fabrication methods, characterization approaches, as well as the properties and applications of FUN-membrane materials. [Copyright &y& Elsevier]

[Display omitted] • Metal organic framework-biomineralized DNA nanospheres were developed as CDT agent. • This CDT agent served as nanoenzyme for boosting the intracellular H 2 O 2 concentration. • Tumor acid-activable cascade reactions were exploited for elevating the ROS level in tumor cells. • This therapeutic platform achieved prominent therapeutic efficacy in both in vitro and in vivo assays. Chemodynamic therapy (CDT) has emerged as an innovative treatment strategy for cancer therapy, and yet most of current systems are highly dependent on endogenous H 2 O 2 for hydroxyl radical (OH) generation, leading to limited therapeutic efficacy. Therefore, it is of significant importance to develop CDT agents with efficient H 2 O 2 self-supplying ability for enhanced CDT efficacy. Herein, we report metal organic framework (MOF)-biomineralized DNA nanospheres as CDT agent engineered with tumor-activable cascade reactions for boosting the intracellular H 2 O 2 concentration, thus achieving remarkable antitumor outcome. As a result of tumor acid-induced dissociation of CDT agent, the released Fe2+/Fe3+ triggers Fenton reaction to produce OH and the released GOx enables to catalyze glucose into H 2 O 2 , which synergistically elevates the ROS level in tumor cells and induces ferroptosis. By exploitation of tumor acid-activable cascade reactions for supplying sufficient H 2 O 2 , our CDT agent achieves prominent therapeutic efficacy in both in vitro and in vivo assays. Our work provides a promising strategy to develop CDT agents for improved CDT efficacy. [ABSTRACT FROM AUTHOR]

DNA nanostructures are emerging as a versatile platform for controlled drug delivery as a result of recent progress in production yield and strategies to obtain prolonged stability in biological environments. The construction of nanostructures from this unique biomaterial provides unparalleled control over structural and functional parameters. Recent applications of DNA origami-based nanocarriers for therapeutic drug delivery in preclinical phases highlight them as promising alternatives to conventional nanomaterials, as they benefit from the inherent favorable properties of DNA including biocompatibility and precise spatial addressability. By incorporating targeting aptamers and responsive properties into the nanocarrier design, more selective DNA origami-based nanocarriers are successfully prepared. On the other hand, current systems remain poorly understood in terms of biodistribution, final fate, and controlled drug release. As such, advances are needed to translate this material platform in its full potential for therapeutic applications. [Display omitted] • Advances in prolonged stability of DNA origami allow biomedical applications. • Drug delivery can benefit from the high programmability and biocompatibility of DNA. • Targeting aptamers and responsive drug release enhance drug selectivity. • DNA origami biodistribution and controlled drug release need better understanding. • Surprisingly, DNA origami nanostructure production costs will not hinder translation. [ABSTRACT FROM AUTHOR]

• DNA is used as a universal substrate to develop diverse engineering systems to improve human and environmental health. • The recent progress on the DNA-based engineering systems used in identification, detection, and treatment is summarized. • Future challenges and opportunities in the development of the DNA-based engineering system are provided. Water pollution and the global spread of pathogens pose unexpected and considerable challenges to human and environmental health. Recent developments in DNA-based engineering systems show various real-world applications in ecosystem restoration, medical diagnostics, immune regulation, and drug delivery, providing new opportunities to address these challenges. DNA materials are essentially different from non-biological materials and act as a robust molecular building block with exceptional attributes; these attributes include its genetic function, biocompatibility, nanoscale controllability, programmability, and molecular recognition capability. Unlike traditional systems using separate strategies, the unique properties of DNA molecules enable their use as universal substrates to develop diverse engineering systems and offer a flexible solution concept to current challenges. Here, we outline principles and approaches for the use of three DNA-based engineering subsystems—DNA tracers, DNA barcodes, and DNA hydrogels—in improving human and environmental health in the context of pollution identification, pathogen detection, and medical treatment, with some discussion of typical examples to highlight the focus of current research and envision potential development direction. We believe that this review will contribute to the rational design of DNA-based tracer, barcode and hydrogel system, and the successful integration of these subsystems that are intrinsically interconnected will further demonstrate their synergistic effects on environmental remediation and medical care. [ABSTRACT FROM AUTHOR]