The recent decades have seen a surge of new nanomaterials designed for efficient drug delivery. DNA nanotechnology has been developed to construct sophisticated 3D nanostructures and artificial ...molecular devices that can be operated at the nanoscale, giving rise to a variety of programmable functions and fascinating applications. In particular, DNA‐origami nanostructures feature rationally designed geometries and precise spatial addressability, as well as marked biocompatibility, thus providing a promising candidate for drug delivery. Here, the recent successful efforts to employ self‐assembled DNA‐origami nanostructures as drug‐delivery vehicles are summarized. The remaining challenges and open opportunities are also discussed.
Structural DNA nanotechnology provides a biocompatible platform to construct customized nanocarriers. Recent developments of DNA‐origami‐based drug‐delivery systems are summarized. Multifunctional, highly tunable, and biologically amenable, DNA‐based nanomaterials will provide powerful strategies to understand and treat disease.
The precursors of functional biomolecules in living cells are synthesized in a bottom‐up manner and subsequently activated by modification into a delicate structure with near‐atomic precision. DNA ...origami technology provides a promising way to mimic the synthesis of precursors, although mimicking the modification process is a challenge. Herein, a DNA paper‐cutting (DNA kirigami) method to trim origami into designer nanostructures is proposed, where the modification is implemented by a polymerase‐triggered DNA strand displacement reaction. Six geometric shapes are created by cutting rectangular DNA origami. Gel electrophoresis and atomic force microscopy results demonstrate the feasibility and capability of the DNA paper‐cutting method. The proposed DNA paper‐cutting strategy can enrich the toolbox for dynamically transforming DNA origami and has potential applications in biomimetics.
A DNA paper‐cutting (DNA kirigami) method is proposed to trim DNA origami into designer nanostructures, where the trimming is implemented by a polymerase‐triggered DNA strand displacement reaction. Six geometric shapes are created by cutting rectangular DNA origami. Gel electrophoresis and atomic force microscopy results demonstrate the feasibility and capability of the DNA paper‐cutting method.
Improving the stability of DNA origami structures with respect to thermal, chemical, and mechanical demands will be essential to fully explore the real‐life applicability of DNA nanotechnology. Here ...we present a strategy to increase the mechanical resilience of individual DNA origami objects and 3D DNA origami crystals in solution as well as in the dry state. By encapsulating DNA origami in a protective silica shell using sol–gel chemistry, all the objects maintain their structural integrity. This allowed for a detailed structural analysis of the crystals in a dry state, thereby revealing their true 3D shape without lattice deformation and drying‐induced collapse. Analysis by energy‐dispersive X‐ray spectroscopy showed a uniform silica coating whose thickness could be controlled through the precursor concentrations and reaction time. This strategy thus facilitates shape‐controlled bottom‐up synthesis of designable biomimetic silica structures through transcription from DNA origami.
Coating concepts: The resilience of DNA origami objects and crystals has been increased through encapsulation in silica. Energy‐dispersive X‐ray spectroscopy showed a uniform silica coating, whose thickness could be controlled through the reactant concentrations and reaction time. This biomimetic approach is an important step toward shape‐controlled bottom‐up synthesis.
DNA Origami
In article number 2308776, Chalmers Chau, Christoph Wälti, and co‐workers introduce the use of solid‐phase reversible immobilization (SPRI) beads as a scalable, high‐throughput, and ...automatable purification method to scale up the production of DNA origami nanostructures, with the aid of liquid handling robot. This artwork illustrates a DNA origami structure in the center and below a robot whose silhouette represents the unification of DNA nanotechnology and modern robotic.
As an important part of driving natural life systems, the function of protein networks is accurately controlled through many parameters, like distance, quantity, position, and orientation. ...Nevertheless, it would be very hard to control the physical arrangement of the multiple proteins to generate cellular signaling events or complex enzymatic cascades, for instance small molecule organic synthesis DNA nanotechnology provides matching nanoscale dimensions, the special programmability of DNA, and the capability and compatibility of many proteins and nucleic acids. DNA origami has precise addressing capabilities at the nanoscale, which ensures the accurate assembly of the protein networks. These characteristics indicate that the DNA origami is a highly addressable programmable nanomaterial, which can be applied for building artificial protein networks. Up to now, researchers have achieved significant progress in the establishment and application of the DNA origami‐protein networks. In the current review, we introduce the superiorities of DNA origami‐protein networks in detail, concluded their construction strategies, and their recent progression and applications in biomedicine and biophysics. In the end, we look into the future prospects of DNA origami‐protein networks. Finally, we looked forward to the future perspective of DNA origami‐protein networks.
The staple strands (ssDNA strands) are able to self‐assembly with scaffold strands to create 2D, 3D DNA origami base. Programmatically conjugate of desired protein onto these DNA origami can achieve the goal of addressable precise assembly of protein networks.
Artificial nanorobots that can recognize molecular triggers and respond with programable operations provide an inspiring proof‐of‐principle for personalized theragnostic applications. We have ...constructed an intelligent DNA nanorobot for autonomous blood anticoagulation in human plasma. The DNA nanorobot comprises a barrel‐shaped DNA nanostructure as the framework and molecular reaction cascades embedded as the computing core. This nanorobot can intelligently sense the concentration of thrombin in the local environment and trigger an autonomous anticoagulation when excess thrombin is present. The triggering concentration of thrombin at which the nanorobot responds can be tuned arbitrarily to avoid possible side effects induced by excess thrombin. This makes the nanorobot useful for autonomous anticoagulation in various medical scenarios and inspires a more efficient and safer strategy for future personalized medicine.
A DNA nanorobot is presented that can intelligently regulate thrombin functions when it senses an over‐boosted coagulation environment. Under normal coagulation conditions it does not perform. The trigger concentrations of nanorobot can be tuned arbitrarily, which makes the nanorobot useful for autonomous anticoagulation in various medical scenarios and inspires a more efficient and safer strategy for personalized medicine.
DNA origami is a powerful method for the creation of 3D nanoscale objects, and in the past few years, interest in wireframe origami designs has increased due to their potential for biomedical ...applications. In DNA wireframe designs, the construction material is double-stranded DNA, which has a persistence length of around 50 nm. In this work, we study the effect of various design choices on the stiffness versus final size of nanoscale wireframe rods, given the constraints on origami designs set by the DNA origami scaffold size. An initial theoretical analysis predicts two competing mechanisms limiting rod stiffness, whose balancing results in an optimal edge length. For small edge lengths, the bending of the rod’s overall frame geometry is the dominant factor, while the flexibility of individual DNA edges has a greater contribution at larger edge lengths. We evaluate our design choices through simulations and experiments and find that the stiffness of the structures increases with the number of sides in the cross-section polygon and that there are indications of an optimal member edge length. We also ascertain the effect of nicked DNA edges on the stiffness of the wireframe rods and demonstrate that ligation of the staple breakpoint nicks reduces the observed flexibility. Our simulations also indicate that the persistence length of wireframe DNA structures significantly decreases with increasing monovalent salt concentration.
Molecular devices that have an anisotropic periodic potential landscape can be operated as Brownian motors. When the potential landscape is cyclically switched with an external force, such devices ...can harness random Brownian fluctuations to generate a directed motion. Recently, directed Brownian motor-like rotatory movement was demonstrated with an electrically switched DNA origami rotor with designed ratchet-like obstacles. Here, we demonstrate that the intrinsic anisotropy of DNA origami rotors is also sufficient to result in motor movement. We show that for low amplitudes of an external switching field, such devices operate as Brownian motors, while at higher amplitudes, they behave deterministically as overdamped electrical motors. We characterize the amplitude and frequency dependence of the movements, showing that after an initial steep rise, the angular speed peaks and drops for excessive driving amplitudes and frequencies. The rotor movement can be well described by a simple stochastic model of the system.
An orthogonal, noncovalent approach to direct the assembly of higher-order DNA origami nanostructures is described. By incorporating perfluorinated tags into the edges of DNA origami tiles we control ...their hierarchical assembly via fluorous-directed recognition. When we combine this approach with Watson–Crick base-pairing we form discrete dimeric constructs in significantly higher yield (8x) than when either molecular recognition method is used in isolation. This integrated “catch-and-latch” approach, which combines the strength and mobility of the fluorous effect with the specificity of base-pairing, provides an additional toolset for DNA nanotechnology, one that enables increased assembly efficiency while requiring significantly fewer DNA sequences. As a result, our integration of fluorous-directed assembly into origami systems represents a cheap, atom-efficient means to produce discrete superstructures.
The stiffness of the cardiovascular environment changes during ageing and in disease and contributes to disease incidence and progression. Changing collagen expression and cross-linking regulate the ...rigidity of the cardiac extracellular matrix (ECM). Additionally, basal lamina glycoproteins, especially laminin and fibronectin regulate cardiomyocyte adhesion formation, mechanics and mechanosignalling. Laminin is abundant in the healthy heart, but fibronectin is increasingly expressed in the fibrotic heart. ECM receptors are co-regulated with the changing ECM. Owing to differences in integrin dynamics, clustering and downstream adhesion formation this is expected to ultimately influence cardiomyocyte mechanosignalling; however, details remain elusive. Here, we sought to investigate how different cardiomyocyte integrin/ligand combinations affect adhesion formation, traction forces and mechanosignalling, using a combination of uniformly coated surfaces with defined stiffness, polydimethylsiloxane nanopillars, micropatterning and specifically designed bionanoarrays for precise ligand presentation. Thereby we found that the adhesion nanoscale organization, signalling and traction force generation of neonatal rat cardiomyocytes (which express both laminin and fibronectin binding integrins) are strongly dependent on the integrin/ligand combination. Together our data indicate that the presence of fibronectin in combination with the enhanced stiffness in fibrotic areas will strongly impact on the cardiomyocyte behaviour and influence disease progression.
This article is part of the theme issue ‘The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease’.
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