Applying dynamic light scattering to investigate the self-assembly process of DNA nanostructures

Understanding the dynamic assembly process of DNA nanostructures is important for developing novel strategy to design and construct functional devices.In this work,temperature-controlled dynamic light scattering(DLS)strategy has been applied to study the global assembly process of DNA origami and DNA bricks.Through the temperature dependent size and intensity profiles,the self-assembly process of various DNA nanostructures with different morphologies have been well-studied and the temperature transition ranges could be observed.Taking advantage of the DLS information,rapid preparation of the DNA origami and the brick assembly has been realized through a constant temperature annealing.Our results demonstrate that the DLS-based strategy provides a convenient and robust tool to study the dynamic process of forming hieratical DNA structures,which will benefit understanding the mechanism of self-assembly of DNA nanostructures.

DNA nanostructures prevent the formation of and convert toxic amyloid proteospecies into cytocompatible and biodegradable spherical complexes

The deposition of insoluble proteinaceous aggregates in the form of amyloidfibrils within the extracellular space of tissues is associated with numerous diseases.The development of molecular approaches to arrest amyloid formation and prevent cel-lular degeneration remains very challenging due to the complexity of the process of protein aggregation,which encompasses an infinite array of conformations and quaternary structures.Polyanionic biopolymers,such as glycosaminoglycans and RNAs,have been shown to modulate the self-assembly of amyloidogenic polypep-tides and to reduce the toxicity induced by the formation of oligomeric and/or pre-fibrillar proteospecies.This study evaluates the effects of double-stranded DNA(dsDNA)nanostructures(1D,2D,and 3D)on amyloid self-assembly,fibril dis-aggregation,and the cytotoxicity associated with amyloidogenesis.Using the islet amyloid polypeptide(IAPP)whose pancreatic accumulation is the hallmark of type 2 diabetes,it was observed that dsDNA nanostructures inhibit amyloid formation by inducing the formation of spherical complexes in which the peptide adopts a random coil conformation.Interestingly,the DNA nanostructures showed a per-sistent ability to disassemble enzymatically and thermodynamically stable amyloidfibrils into nanoscale DNA/IAPP entities that are fully compatible withβ-pancreatic cells and are biodegradable by proteolysis.Notably,dsDNA nanostructures avidly trapped highly toxic soluble oligomeric species in complete cell culture media and converted them into non-toxic binary complexes.Overall,these results expose the potent modulatory effects of dsDNA on amyloidogenic pathways,and these DNA nanoscaffolds could be used as a source of inspiration for the design of molecules tofight amyloid-related disorders.

Preparation of Long-range Ordered Nanostructures in Semicrystalline Diblock Copolymer Thin Films Using Micromolding

Long-range ordered nanostructures are prepared in the poly（styrene）-block-poly（e-caprolactone） diblock copolymer thin films using micromolding. We evaluated the change in crystallinity based on grazing-incidence X-ray diffraction and proved that the crystallinity increased with the decrease of the mold size. This means that ordered nanostructures with atomic length scale order can be adjusted by tuning the mesoscale confinement. The inherent mechanism was the cooperation of geometric confinement, microphase structure and surface-induced ordering of PS-b-PCL in the melt, which paved the way for the subsequent crystal growth. These findings establish a route to promote the cost-effective nanofabrication by combining the mature microfabrication technique with the emerging directed self-assembly of block copolymers.

Controlling DNA Bundle Size and Spatial Arrangement in Selfassembled Arrays on Superhydrophobic Surface

The use of superhydrophobic surfaces(SHSs) is now emerging as an attractive platform for the realization of one-dimensional(1D) nanostructures with potential applications in many nanotechnological and biotechnological fields.To this purpose, a strict control of the nanostructures size and their spatial arrangement is highly required. However, these parameters may be strongly dependent on the complex evaporation dynamics of the sessile droplet on the SHS. In this work, we investigated the effect of the evaporation dynamics on the size and the spatial arrangement of self-assembled 1D DNA bundles. Our results reveal that different arrangements and bundle size distributions may occur depending on droplet evaporation stage. These results contribute to elucidate the formation mechanism of 1D nanostructures on SHSs.

Discrete DNA Three-dimensional Nanostructures： the Synthesis and Applications

Structural DNA nanotechnology, an emerging technique that utilizes the nucleic acid molecule as generic polymer to programmably assemble well-defined and nano-sized architectures, holds great promise for new material synthesis and constructing functional nanodevices for different purposes. In the past three decades, rapid development of this technique has enabled the syntheses of hundreds and thousands of DNA nanostructures with various morphologies at different scales and dimensions. Among them, discrete three-dimensional （3D） DNA nanostructures not only represent the most advances in new material design, but also can serve as an excellent platform for many important applications. With precise spatial addressability and capability of arbitrary control over size, shape, and function, these nanostructures have drawn particular interests to scientists in different research fields. In this review article, we will briefly summarize the development regarding the synthesis of discrete DNA 3D nanostructures with various size, shape, geometry, and topology, including our previous work and recent progress by other groups. In detail, three methods majorly used to synthesize the DNA 3D objects will be introduced accordingly. Additionally, the principle, design rule, as well as pros and cons of each method will be highlighted. As functions of these discrete 3D nanostructures have drawn great interests to researchers, we will further discuss their cutting-edge applications in different areas, ranging from novel material synthesis, new device fabrication, and biomedical applications, etc. Lastly, challenges and outlook of these promising nanostructures will be given based on our point of view.

Functionalizing DNA nanostructures with natural cationic amino acids

Complexing self-assembled DNA nanostructures with various functional guest species is the key to unlocking new and exciting biomedical applications.Cationic guest species not only induce magnesium-free DNA to self-assemble into defined structures but also endow the final complex nanomaterials with new properties.Herein,we propose a novel strategy that employs naturally occurring cationic amino acids to induce DNA self-assembly into defined nanostructures.Natural L-arginine and L-lysine can readily induce the assembly of tile-based DNA nanotubes and DNA origami sheets in a magnesium-free manner.The self-assembly processes are demonstrated to be pH-and concentration-dependent and are achieved at constant temperatures.Moreover,the assembled DNA/amino acid complex nanomaterials are stable at a physiological temperature of 37◦C.Substituting L-arginine with its D form enhances its serum stability.Further preliminary examination of this complex nanomaterial platform for biomedical applications indicates that DNA/amino acids exhibit distinct cellular uptake behaviors compared with their magnesium-assembled counterparts.The nanomaterial mainly clusters around the cell membrane and might be utilized to manipulate molecular events on the membrane.Our study suggests that the properties of DNA nanostructures can be tuned by complexing them with customized guest molecules for a designed application.The strategy proposed herein might be promising to advance the biomedical applications of DNA nanostructures.

Bioimaging Based on Nucleic Acid Nanostructures

Nucleic acid nanostructures with structural programmability, spatial addressability and excellent biocompatibility have drawn much attention in various biomedical applications, such as bioimaging, biosensing and drug delivery. In this review, we summarize the recent research progress in the field of bioimaging based on nucleic acid nanostructures with different imaging models, including fluorescent imaging(FI), magnetic resonance imaging(MRI), photoacoustic imaging(PAI) and positron emission tomography/computed tomography(PET/CT) imaging. We also discuss the remaining challenges and further opportunities involved in the bioimaging research based on nucleic acid nanostructures.

Recent progress on DNA block copolymer

DNA has gained great attention because of its unique structure,excellent molecular recognition property,and biological functions.When married with versatile synthetic polymers,the DNA conjugated polymer hybrids,known as DNA block copolymers（DBCs）,have been launched and well developed for the syntheses of new materials and nanostructures with different functions in the past several decades.Compared to conventional synthetic block copolymers,using DNA as a building block provides several advantages over other polymer candidates,such as molecular recognition,programmable self-assembly,biocompatibility,and sequence-encoded information.In this review,recent developments in this area will be summarized and meaningful breakthroughs will be highlighted.We will discuss representative examples of recent progress in the syntheses,structure manipulations,and applications of DBCs.

Logic-Gated Plasmonic Nanodevices Based on DNA-Templated Assembly

Life has evolved numerous elegant molecular machines that recognize biological signals and affect mechanical changes precisely to achieve specific and versatile biofunctions.Inspired by nature,synthetic molecular machines could be designed rationally to realize nanomechanical operations and autonomous computing.We constructed logic-gated plasmonic nanodevices through coassembly of two gold nanorods(AuNRs)and computing elements on a tweezer-shaped DNA origami template.After recognition of various molecular inputs,such as DNA strands,glutathione,or adenosine,the geometry and plasmonic circular dichroism(CD)signals of the AuNR–origami nanodevices produced corresponding changes.Then we designed and characterized a set of modular Boolean logic-gated nanodevices(YES,NOT,AND,OR)and proceeded to construct a complicated 3-input circuit capable of performing Boolean OR-NOT-AND operations.Our plasmonic logic devices transduced external inputs into conformational changes and near-infrared(NIR)chiral outputs.This DNA-based self-assembly strategy holds great potential for applications in programmable optical modulators,molecular information processing,and bioanalysis.

Nucleobase,nucleoside,nucleotide,and oligonucleotide coordinated metal ions for sensing and biomedicine applications

Metal ions play critical roles in chemical,biological,and environmental processes.Various biomolecules have the ability to coordinate with metal ions and form various materials.Nucleobases,nucleosides,and nucleotides,as the essential components of DNA,have emerged as a useful building block for the construction of functional nanomaterials.In recent years,DNA oligonucleotides have also been used for this purpose.We herein review the strategies for the synthesis of soft nanomaterials through the assembly of nucleotides(or DNA)and metal ions to yield various nanoparticles,fibers,and hydrogels.Such coordination methods are simple to operate and can be carried out under ambient conditions.The luminescent,catalytic,and molecular recognition properties of these coordination materials are described with representative recent examples.Their applications ranging from biosensing,enzyme encapsulation,catalysis,templated shell growth to cancer therapy are highlighted.Finally,challenges of this field and future perspectives are discussed.

Pharmaceutical applications of framework nucleic acids

DNA is a biological polymer that encodes and stores genetic information in all living organism. Particularly, the precise nucleobase pairing inside DNA is exploited for the self-assembling of nanostructures with defined size, shape and functionality. These DNA nanostructures are known as framework nucleic acids(FNAs) for their skeleton-like features. Recently, FNAs have been explored in various fields ranging from physics, chemistry to biology. In this review, we mainly focus on the recent progress of FNAs in a pharmaceutical perspective. We summarize the advantages and applications of FNAs for drug discovery, drug delivery and drug analysis. We further discuss the drawbacks of FNAs and provide an outlook on the pharmaceutical research direction of FNAs in the future.