Deoxyribonucleic Acid Nanostructures Research Articles

Recent advances in DNA nanomaterials for cancer diagnosis and treatment

Abstract The elucidation of the structural characteristics of deoxyribonucleic acid (DNA) by Watson and Crick, the advent of polymerase chain reaction technology, and the development of primer-synthesis methods, enable DNA to be replicated and transformed in an increasingly easy manner, such that it is among the most directed and evolving nanomaterials in molecular biology. Traditional cancer diagnosis methods are somewhat limited and are unable to meet existing needs; consequently, DNA nanostructures with wide ranging properties are receiving increasingly more attention because a number of DNA materials have been shown to exhibit diagnostic properties. Some DNA materials can functionally alter the biological behavior of cells, such as cell migration, cell proliferation, cell differentiation, autophagy, and anti-inflammatory effects. Some single-stranded DNA or ribonucleic acid with secondary structure through self-pairing, called aptamer, systematic evolution of ligands by exponential enrichment (SELEX), have targeting capabilities and can be applied to tumor targeted diagnosis and therapy. Several DNA nanomaterials with three-dimensional nanostructures and stable structures are being investigated as drug carrier systems to act on a variety of antitumor drugs or gene therapy agents. This article reviews the use of functionalized DNA nanostructures in cancer diagnosis and treatment applications. Various biosensors and carriers based on DNA nanostructures are introduced and chemical reactions related to the preparation of the carrier and the signal transduction mechanism of the sensor are discussed. Efficient carrier/biosensor platforms based on various structural developments and current DNA nanomaterial developments are also presented.

Small Molecule-Templated DNA Hydrogel with Record Stiffness Integrates and Releases DNA Nanostructures and Gene Silencing Nucleic Acids.

Deoxyribonucleic acid (DNA) hydrogels are a unique class of programmable, biocompatible materials able to respond to complex stimuli, making them valuable in drug delivery, analyte detection, cell growth, and shape-memory materials. However, unmodified DNA hydrogels in the literature are very soft, rarely reaching a storage modulus of 103 Pa, and they lack functionality, limiting their applications. Here, a DNA/small-molecule motif to create stiff hydrogels from unmodified DNA, reaching 105 Pa in storage modulus is used. The motif consists of an interaction between polyadenine and cyanuric acid-which has 3-thymine like faces-into multimicrometer supramolecular fibers. The mechanical properties of these hydrogels are readily tuned, they are self-healing and thixotropic. They integrate a high density of small, nontoxic molecules, and are functionalized simply by varying the molecule sidechain. They respond to three independent stimuli, including a small molecule stimulus. These stimuli are used to integrate and release DNA wireframe and DNA origami nanostructures within the hydrogel. The hydrogel is applied as an injectable delivery vector, releasing an antisense oligonucleotide in cells, and increasing its gene silencing efficacy. This work provides tunable, stimuli-responsive, exceptionally stiff all-DNA hydrogels from simple sequences, extending these materials' capabilities.

Emerging Approaches to DNA Data Storage: Challenges and Prospects.

With the total amount of worldwide data skyrocketing, the global data storage demand is predicted to grow to 1.75 × 1014 GB by 2025. Traditional storage methods have difficulties keeping pace given that current storage media have a maximum density of 103 GB/mm3. As such, data production will far exceed the capacity of currently available storage methods. The costs of maintaining and transferring data, as well as the limited lifespans and significant data losses associated with current technologies also demand advanced solutions for information storage. Nature offers a powerful alternative through the storage of information that defines living organisms in unique orders of four bases (A, T, C, G) located in molecules called deoxyribonucleic acid (DNA). DNA molecules as information carriers have many advantages over traditional storage media. Their high storage density, potentially low maintenance cost, ease of synthesis, and chemical modification make them an ideal alternative for information storage. To this end, rapid progress has been made over the past decade by exploiting user-defined DNA materials to encode information. In this review, we discuss the most recent advances of DNA-based data storage with a major focus on the challenges that remain in this promising field, including the current intrinsic low speed in data writing and reading and the high cost per byte stored. Alternatively, data storage relying on DNA nanostructures (as opposed to DNA sequence) as well as on other combinations of nanomaterials and biomolecules are proposed with promising technological and economic advantages. In summarizing the advances that have been made and underlining the challenges that remain, we provide a roadmap for the ongoing research in this rapidly growing field, which will enable the development of technological solutions to the global demand for superior storage methodologies.

Therapeutic Applications of Programmable DNA Nanostructures.

Deoxyribonucleic acid (DNA) nanotechnology, a frontier in biomedical engineering, is an emerging field that has enabled the engineering of molecular-scale DNA materials with applications in biomedicine such as bioimaging, biodetection, and drug delivery over the past decades. The programmability of DNA nanostructures allows the precise engineering of DNA nanocarriers with controllable shapes, sizes, surface chemistries, and functions to deliver therapeutic and functional payloads to target cells with higher efficiency and enhanced specificity. Programmability and control over design also allow the creation of dynamic devices, such as DNA nanorobots, that can react to external stimuli and execute programmed tasks. This review focuses on the current findings and progress in the field, mainly on the employment of DNA nanostructures such as DNA origami nanorobots, DNA nanotubes, DNA tetrahedra, DNA boxes, and DNA nanoflowers in the biomedical field for therapeutic purposes. We will also discuss the fate of DNA nanostructures in living cells, the major obstacles to overcome, that is, the stability of DNA nanostructures in biomedical applications, and the opportunities for DNA nanostructure-based drug delivery in the future.

Construction and applications of DNA-based nanomaterials in cancer therapy

As a biologically active macromolecule, deoxyribonucleic acid (DNA) has the advantages of sequence programmability and structure controllability and can accurately transmit sequence information to specific biological functions. Facing the complex internal microenvironment and heterogeneity in tumor treatment, the construction and applications of DNA-based nanomaterials have become a focus point of research. In particular, the hybridization of DNA molecules with other materials endows DNA-based nanomaterials with multiple functions such as targeting, stimulus responsiveness and regulations of biological activities, making DNA nanostructures great potential in the treatment of major human diseases. In this review, the construction and characteristics of DNA-based nanomaterials are introduced. Then, the functions and applications of DNA-based nanomaterials in the delivery of chemotherapy drugs and gene drugs, stimulus-responsive release and regulation of cell homeostasis are reviewed. Finally, the future development and challenges of DNA-based nanomaterials are prospected. We envision that DNA-based nanomaterials can enrich the nanomaterial system by rational design and synthesis and address the growing demands on biological and biomedical applications in the real world.

DNA‐organic molecular amphiphiles: Synthesis, self‐assembly, and hierarchical aggregates

AbstractWith the development of deoxyribonucleic acid (DNA) nanotechnology, various DNA nanostructures and DNA devices have been constructed, which exhibit potential applications in material science and biomedicine. Taking advantage of the programmability and biocompatibility of DNA, novel building block to chemically functionalize DNA with hydrophobic organic molecules has attracted more and more attention. Driving by amphiphilicity, DNA‐organic molecular amphiphiles have been demonstrated to self‐assemble or further induce hierarchically assemblies, providing novel‐specific properties. In this minireview, we summarize the recent progress of DNA organic molecular amphiphiles including their synthesis, self‐assembly behavior in aqueous solution, and the amphiphilic self‐assembly based on hierarchical DNA nano‐structures. We further briefly discuss the perspective of the application of the DNA‐organic molecular amphiphiles.

Image Encoding Using Multi-Level DNA Barcodes with Nanopore Readout.

Deoxyribonucleic acid (DNA) nanostructure-based data encoding is an emerging information storage mode, offering rewritable, editable, and secure data storage. Herein, a DNA nanostructure-based storage method established on a solid-state nanopore sensing platform to save and encrypt a 2D grayscale image is proposed. DNA multi-way junctions of different sizes are attached to a double strand of DNA carriers, resulting in distinct levels of current blockades when passing through a glass nanopore with diameters around 14nm. The resulting quaternary encoding doubles the capacity relative to a classical binary system. Through toehold-mediated strand displacement reactions, the DNA nanostructures can be precisely added to and removed from the DNA carrier. By encoding the image into 16 DNA carriers using the quaternary barcodes and reading them in one simultaneous measurement, the image is successfully saved, encrypted, and recovered. Avoiding any proteins or enzymatic reactions, the authors thus realize a pure DNA storage system on a nanopore platform with increased capacity and programmability.

Constructing Large 2D Lattices Out of DNA-Tiles.

The predictable nature of deoxyribonucleic acid (DNA) interactions enables assembly of DNA into almost any arbitrary shape with programmable features of nanometer precision. The recent progress of DNA nanotechnology has allowed production of an even wider gamut of possible shapes with high-yield and error-free assembly processes. Most of these structures are, however, limited in size to a nanometer scale. To overcome this limitation, a plethora of studies has been carried out to form larger structures using DNA assemblies as building blocks or tiles. Therefore, DNA tiles have become one of the most widely used building blocks for engineering large, intricate structures with nanometer precision. To create even larger assemblies with highly organized patterns, scientists have developed a variety of structural design principles and assembly methods. This review first summarizes currently available DNA tile toolboxes and the basic principles of lattice formation and hierarchical self-assembly using DNA tiles. Special emphasis is given to the forces involved in the assembly process in liquid-liquid and at solid-liquid interfaces, and how to master them to reach the optimum balance between the involved interactions for successful self-assembly. In addition, we focus on the recent approaches that have shown great potential for the controlled immobilization and positioning of DNA nanostructures on different surfaces. The ability to position DNA objects in a controllable manner on technologically relevant surfaces is one step forward towards the integration of DNA-based materials into nanoelectronic and sensor devices.

DNA Structural Barcode Copying and Random Access

Digitally encoded deoxyribonucleic acid (DNA) nanostructures built via DNA self‐assembly have established applications in multiplexed biosensing and storing digital information. However, a key challenge is that DNA structures are not easily copied which is of vital importance for their large‐scale production and access to desired molecules by target‐specific amplification. Herein, DNA structural barcodes are built and the copying and random access of the barcodes from a library of molecules is demonstrated using a modified polymerase chain reaction (PCR). The structural barcodes are assembled by annealing a single‐stranded DNA scaffold with complementary short oligonucleotides containing protrusions as digital bits at defined locations. DNA nicks in these structures are ligated to facilitate barcode copying using PCR. To randomly access a target from a library of barcodes, a non‐complementary end in the DNA construct that serves as a barcode‐specific primer‐template is used. Readout of the DNA structural barcodes is performed with nanopore measurements. The study provides a roadmap for the convenient production of large quantities of self‐assembled DNA nanostructures. In addition, this strategy offers access to specific targets, a crucial capability for multiplexed single‐molecule sensing, and DNA data storage.

DNA Electrochemical Biosensors for In Situ Probing of Pharmaceutical Drug Oxidative DNA Damage.

Deoxyribonucleic acid (DNA) electrochemical biosensors are devices that incorporate immobilized DNA as a molecular recognition element on the electrode surface, and enable probing in situ the oxidative DNA damage. A wide range of DNA electrochemical biosensor analytical and biotechnological applications in pharmacology are foreseen, due to their ability to determine in situ and in real-time the DNA interaction mechanisms with pharmaceutical drugs, as well as with their degradation products, redox reaction products, and metabolites, and due to their capacity to achieve quantitative electroanalytical evaluation of the drugs, with high sensitivity, short time of analysis, and low cost. This review presents the design and applications of label-free DNA electrochemical biosensors that use DNA direct electrochemical oxidation to detect oxidative DNA damage. The DNA electrochemical biosensor development, from the viewpoint of electrochemical and atomic force microscopy (AFM) characterization, and the bottom-up immobilization of DNA nanostructures at the electrode surface, are described. Applications of DNA electrochemical biosensors that enable the label-free detection of DNA interactions with pharmaceutical compounds, such as acridine derivatives, alkaloids, alkylating agents, alkylphosphocholines, antibiotics, antimetabolites, kinase inhibitors, immunomodulatory agents, metal complexes, nucleoside analogs, and phenolic compounds, which can be used in drug analysis and drug discovery, and may lead to future screening systems, are reviewed.

Data-driven enzyme immobilisation: a case study using DNA to immobilise galactose oxidase.

Biocatalysis has the potential to enable green chemistry. New methods of enzyme immobilisation will be required to improve enzyme stability, product purification, and compatibility of different enzymes in the same reaction conditions. Deoxyribonucleic acid (DNA) stands out among supramolecular scaffolds, as simple Watson-Crick base-pairing rules can be used to rationally design a unique nanoscale environment around each individual enzyme in a cascade. Enhancements of enzyme activity and stability on DNA nanostructures have previously been reported, but never in the context of industrially relevant chemical syntheses or reaction conditions. Here, the authors show DNA can enhance the activity and stability of a galactose oxidase mutant, which could be used in a cascade to produce bioplastics from lignin. The enzyme was enhanced in the cell-free extract, which to their knowledge has not been shown before for any enzymes on DNA. This is significant because crude biocatalytic reactions are vastly more cost-effective. This opens the door to further work on multienzyme cascades by tuning the properties of individual enzymes.

Toward Sub-Diffraction Imaging of Single-DNA Molecule Sensors Based on Stochastic Switching Localization Microscopy.

The natural characteristics of deoxyribonucleic acid (DNA) enable its advanced applications in nanotechnology as a special tool that can be detected by high-resolution imaging with precise localization. Super-resolution (SR) microscopy enables the examination of nanoscale molecules beyond the diffraction limit. With the development of SR microscopy methods, DNA nanostructures can now be optically assessed. Using the specific binding of fluorophores with their target molecules, advanced single-molecule localization microscopy (SMLM) has been expanded into different fields, allowing wide-range detection at the single-molecule level. This review discusses the recent progress in the SR imaging of DNA nano-objects using SMLM techniques, such as direct stochastic optical reconstruction microscopy, binding-activated localization microscopy, and point accumulation for imaging nanoscale topography. Furthermore, we discuss their advantages and limitations, present applications, and future perspectives.

Functional DNA-based hydrogel intelligent materials for biomedical applications.

Deoxyribonucleic acid (DNA) nanotechnology is a relevant research field of nano-biotechnology, which has developed rapidly in recent years. Researchers have studied DNA far more than they have studied its genetic characteristics, and now it has evolved into the field of nanomedical materials. A variety of articles based on DNA nanostructures can be obtained by rational design and controllable preparation. In particular, intelligent DNA-based hydrogel materials have attracted significant attention as an essential representative of macro DNA materials. They have shown a wide range of applications, especially in the field of biomedical applications. DNA-based hydrogels have many unique and fascinating properties, such as, excellent biocompatibility, biodegradability, basic programmability, catalytic activities, therapeutic potential, and molecular recognition and bonds. The intelligent DNA hydrogel will undergo abrupt changes in the stimulation of temperature, pH value, ionic strength, and solvent composition. These factors can also be used for applications in intelligent materials that play an essential role in biomedical sciences. To date, intelligent DNA hydrogels have been reported for many applications, including controlled drug delivery, targeted gene therapy, cancer therapy, biosensors, protein production, and 3D cell cultures. However, the large-scale production of intelligent DNA hydrogels has not yet been realized, and the synergistic multifunctional integration has not been explored. This review summarizes the current state of DNA nanostructures, especially the intelligent DNA-based hydrogel materials, and focuses on design and engineering for bio-responsive use and proposes some reasonable prospects for the future development of intelligent DNA-based hydrogel materials.

Band gap, dielectric constant, and susceptibility of DNA layers as controlled by vanadium ion concentration

Deoxyribonucleic acid (DNA) doped with transition metal ions shows great versatility for molecular-based biosensors and bioelectronics. Methodologies for developing DNA lattices (formed by synthetic double-crossover tiles) and DNA layers (used by natural salmon) doped with vanadium ions (V3+), as well as an understanding of the physical characteristics of V3+-doped DNA nanostructures, are essential in practical applications in interdisciplinary research fields. Here, DNA lattices and layers doped with V3+ are constructed through substrate-assisted growth and drop-casting methods. In addition, enhanced physical characteristics such as the band gap energy, work function, dielectric constant, and susceptibility of V3+-doped DNA nanostructures with varying V3+ concentration ([V3+]) are investigated. The critical concentration ([V3+]C) at a given amount of DNA was predicted based on an analysis of the phase transition of DNA lattices from crystalline to amorphous with specific [V3+]. Generally, the [V3+]C provided crucial information on the structural stability and extremum physical characteristics of V3+-doped DNA nanostructures due to the optimum incorporation of V3+ into DNA. We obtained the optical absorption spectra for energy band gap estimation; Raman spectra for identifying the preferential coordination sites of V3+ in DNA; x-ray photoelectron spectra to examine the chemical state, chemical composition, and functional groups; and ultraviolet photoelectron spectra to estimate the work function. In addition, we addressed the electrical properties (i.e. current, capacitance, dielectric constant, and storage energy) and magnetic properties (magnetic field-dependent and temperature-dependent magnetizations and susceptibility) of DNA layers in the presence of V3+. The development of biocompatible materials with specific optical, electrical, and magnetic properties is required for future applications because they must have designated functionality, high efficiency, and affordability.

DNA nanostructures doped with lanthanide ions for highly sensitive UV photodetectors.

Deoxyribonucleic acid (DNA) and lanthanide ions (Ln3+) exhibit exceptional optical properties that are applicable to the development of nanoscale devices and sensors. Although DNA nanostructures and Ln3+ ions have been investigated for use in the current state of technology for more than a few decades, researchers have yet to develop DNA and Ln3+ based ultra-violet (UV) photodetectors. Here, we fabricate Ln3+ (such as holmium (Ho3+), praseodymium (Pr3+), and ytterbium (Yb3+))‒doped double crossover (DX)‒DNA lattices through substrate-assisted growth and salmon DNA (SDNA) thin films via a simple drop-casting method on oxygen (O2) plasma-treated substrates for high performance UV photodetectors. Topological (AFM), optical (UV-vis absorption and FTIR), spectroscopic (XPS), and electrical (I‒V and photovoltage) measurements of the DX‒DNA and SDNA thin films doped with various concentrations of Ln3+ ([Ln3+]) are explored. From the AFM analysis, the optimum concentrations of various Ln3+ ([Ln3+]O) are estimated (where the phase transition of Ln3+‒doped DX‒DNA lattices takes place from crystalline to amorphous) as 1.2 mM for Ho3+, 1.5 mM for Pr3+, and 1.5 mM for Yb3+. The binding modes and chemical states are evaluated through optical and spectroscopic analysis. From UV-vis absorption studies, we found that as the [Ln3+] was increased, the absorption intensity decreased up to [Ln3+]O, and increased above [Ln3+]O. The variation in FTIR peak intensities in the nucleobase and phosphate regions, and the changes in XPS peak intensities and peak positions detected in the N 1 s and P 2p core spectra of Ln3+‒doped SDNA thin films clearly indicate that the Ln3+ ions are properly bound between the bases (through chemical intercalation) and to the phosphate backbone (through electrostatic interactions) of the DNA molecules. Finally, the I‒V characteristics and time-dependent photovoltage of Ln3+‒doped SDNA thin films are measured both in the dark and under UV LED illuminations (λLED = 382 nm) at various illumination powers. The photocurrent and photovoltage of Ln3+‒doped SDNA thin films are enhanced up to the [Ln3+]O compared to pristine SDNA due to the charge carriers generated from both SDNA and Ln3+ ions upon the absorption of light. From our observations, the photovoltages as function of illumination power suggest higher responsivities, and the photovoltages as function of time are almost constant which indicates the stability and retention characteristics of the Ln3+‒doped SDNA thin films. Hence, our method which provides an efficient doping of Ln3+ into the SDNA with a simple fabrication process might be useful in the development of high-performance optoelectronic devices and sensors.

Review of the Electrical Characterization of Metallic Nanowires on DNA Templates.

The use of self-assembly techniques may open new possibilities in scaling down electronic circuits to their ultimate limits. Deoxyribonucleic acid (DNA) nanotechnology has already demonstrated that it can provide valuable tools for the creation of nanostructures of arbitrary shape, therefore presenting an ideal platform for the development of nanoelectronic circuits. So far, however, the electronic properties of DNA nanostructures are mostly insulating, thus limiting the use of the nanostructures in electronic circuits. Therefore, methods have been investigated that use the DNA nanostructures as templates for the deposition of electrically conducting materials along the DNA strands. The most simple such structure is given by metallic nanowires formed by deposition of metals along the DNA nanostructures. Here, we review the fabrication and the characterization of the electronic properties of nanowires, which were created using these methods.

Fabrication of Continuous DNA Lattice Structure with Nanofiber Framework

DNA(Deoxyribonucleic acid) is widely used in the fabrication of nanostructures as a nano-material based on the principle of base pair complementarity and has a wide range of applications which involves biology, biophysics, synthetic biology and photonics. However, almost all the structures exhibit a limitation of size which hinders the development of membranes. Here we introduce a new method to manufacturing DNA nanostructures through the combination of DNA lattice and nanofiber. DNA is compiled into a continuous lattice in the size of nanometer and fixed on the framework made up of nanofiber which is also made into grid. We anticipate this method could fabricate a kind of new membranes like nanostructure whose hold size is controllable, and the results of the preliminary experiment reveal the possibility of this method.

Advances in DNA Nanostructure-Based Smart Drug Delivery Systems

Highly specific deoxyribonucleic acid (DNA) base-pairing not only carries genetic information, but also provides the basis for self-assembly of novel nanostructures with programmable shapes and sizes. Unlike single-stranded and double-stranded DNA, DNA nanostructures exhibit good cellular permeability. They also have characteristics of uniform size, easy functionalization, precise addressability, excellent water solubility and high biocompatibility. Due to their unique properties, these tailored molecular devices are ideal nanoscale systems for targeting cells and triggering cellular responses. Recent progress in the field of DNA nanotechnology has demonstrated effectiveness and advantages of DNA nanostructures as smart and targeted drug delivery systems or imaging agents within living organisms. In this review, we summarize the recent advances in structure design, cargo loading and cellular delivery of DNA nanocarriers, and discuss their potential in therapeutic applications.

Self-assembled mirror DNA nanostructures for tumor-specific delivery of anticancer drugs

Nanoparticle delivery systems have been extensively investigated for targeted delivery of anticancer drugs over the past decades. However, it is still a great challenge to overcome the drawbacks of conventional nanoparticle systems such as liposomes and micelles. Various novel nanomaterials consist of natural polymers are proposed to enhance the therapeutic efficacy of anticancer drugs. Among them, deoxyribonucleic acid (DNA) has received much attention as an emerging material for preparation of self-assembled nanostructures with precise control of size and shape for tailored uses. In this study, self-assembled mirror DNA tetrahedron nanostructures is developed for tumor-specific delivery of anticancer drugs. l-DNA, a mirror form of natural d-DNA, is utilized for resolving a poor serum stability of natural d-DNA. The mirror DNA nanostructures show identical thermodynamic properties to that of natural d-DNA, while possessing far enhanced serum stability. This unique characteristic results in a significant effect on the pharmacokinetics and biodistribution of DNA nanostructures. It is demonstrated that the mirror DNA nanostructures can deliver anticancer drugs selectively to tumors with enhanced cellular and tissue penetration. Furthermore, the mirror DNA nanostructures show greater anticancer effects as compared to that of conventional PEGylated liposomes. Our new approach provides an alternative strategy for tumor-specific delivery of anticancer drugs and highlights the promising potential of the mirror DNA nanostructures as a novel drug delivery platform.

Interfacing DNA nanodevices with biology: challenges, solutions and perspectives

The cellular machinery performs millions of complex reactions with extreme precision at nanoscale. From studying these reactions, scientists have become inspired to build artificial nanosized molecular devices with programmed functions. One of the fundamental tools in designing and creating these nanodevices is molecular self-assembly. In nature, deoxyribonucleic acid (DNA) is inarguably one of the most remarkable self-assembling molecules. Governed by the Watson–Crick base-pairing rules, DNA assembles with a structural reliability and predictability based on sequence composition unlike any other complex biological polymer. This consistency has enabled rational design of hundreds of two- and three-dimensional shapes with a molecular precision and homogeneity not preceded by any other known technology at the nanometer scale.During the last two decades, DNA nanotechnology has undergone a rapid evolution pioneered by the work of Nadrian Seeman (Kallenbach et al 1983 Nature 205 829–31). Especially the introduction of the versatile DNA Origami technique by Rothemund (2006 Nature 440 297–302) led to an efflorescence of new DNA-based self-assembled nanostructures (Andersen et al 2009 Nature 459 73–6, Douglas et al 2009 Nature 459 414–8, Dietz et al 2009 Science 325 725–30, Han et al 2011 Science 332 342–6, Iinuma et al 2014 Science 344 65–9), and variations of this technique have contributed to an increasing repertoire of DNA nanostructures (Wei et al 2012 Nature 485 623–6, Ke et al 2012 Science 338 1177–83, Benson et al 2015 Nature 523 441–4, Zhang et al 2015 Nat. Nanotechnol. 10 779–84, Scheible et al 2015 Small 11 5200–5). These advances have naturally triggered the question: What can these DNA nanostructures be used for?One of the leading proposals of use for DNA nanotechnology has been in biology and biomedicine acting as a molecular ‘nanorobot’ or smart drug interacting with the cellular machinery. In this review, we will explore and examine the perspective of DNA nanotechnology for such use. We summarize which requirements DNA nanostructures must fulfil to function in cellular environments and inside living organisms. In addition, we highlight recent advances in interfacing DNA nanostructures with biology.