3D Lattice Engineering of Nanoparticles by DNA Shells

With the development of structural DNA nanotechnology, DNA has now far exceeded its original function: as a genetic code. It can, in principle, self‐assemble into desired shapes with accurate size. Moreover, it can perform as a functional linker to program other materials by grafting DNA onto these materials. Nanoparticles, both inorganic and organic, can now be programmatically assembled into complex 3D superlattices with high order when guided by DNA. By encoding functions into the as‐assembled nanoparticles, materials with excellent collective effects may be invented. Here, how nanoparticles with different shapes or functions are successfully fabricated into 3D lattices with the help of DNA shells coated on the surface and how scientists can produce desired lattices by design are reviewed. The cases to achieve dynamic superlattices of nanoparticles by affecting the environment where DNA survives are also discussed.     

Controlling the formation of DNA origami structures with external signals

Degradable Newkome-type and polylysine dendrons functionalized with spermine surface units are used to control the formation of DNA origami structures. The intact dendrons form polyelectrolyte complexes with the scaffold strands, therefore blocking the origami formation. Degradation of the dendron with an optical trigger or chemical reduction leads to the release of the DNA scaffold and efficient formation of the desired origami structure. These results provide new insights towards realizing responsive materials with DNA origami.     

Orthogonal protein decoration of DNA nanostructures

The development of robust DNA-protein coupling techniques is mandatory for applications of DNA nanostructures in biomedical diagnostics, fundamental biochemistry, and other fields in biomolecular nanosciences. The use of self-labeling fusion proteins, which are orthogonal to biotin-streptavidin and antibody-antigen interactions, is described for the site-selective protein decoration of two exemplary DNA nanostructures: a four-way junction X-tile motif and a 3D DNA tetrahedron. Multifunctional DNA superstructures bearing up to four different proteins are generated and characterized by electrophoresis and microplate-based functionality assays. Steric and electrostatic interactions are identified as critical parameters controlling the efficiency of DNA-protein ligation. The results indicate that this method is versatile and broadly applicable, not only for the functionalization of DNA architectures but also for the site-specific decoration of other molecular materials and devices containing several different proteins.     

Self‐Assembly of Microparticles by Supramolecular Homopolymerization of One Component DNA Molecule

DNA is a superb molecule for self‐assembly of nanostructures. Often many DNA strands are required for the assembly of one DNA nanostructure. For lowering the cost of synthesizing DNA strands and facilitating the assembly process, it is highly desirable to use a minimal number of unique strands for potential technological applications. Herein, a strategy is reported to assemble a series of DNA microparticles (DNAµPs) from one component DNA strand. As a demonstration of the application of the resulting DNAµPs, the design and assembled DNAµPs are modified to carry additional single‐stranded tails on their surfaces. The modified DNAµPs can either capture other nucleic acids or display CpG motifs to stimulate immune responses.     

Rationally Designed DNA‐Origami Nanomaterials for Drug Delivery In Vivo

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.     

A DNA Origami Mechanical Device for the Regulation of Microcosmic Structural Rigidity

DNA origami makes it feasible to fabricate a tremendous number of DNA nanostructures with various geometries, dimensions, and functionalities. Moreover, an increasing amount of research on DNA nanostructures is focused on biological and biomedical applications. Here, the reversible regulation of microcosmic structural rigidity is accomplished using a DNA origami device in vitro. The designed DNA origami monomer is composed of an internal central axis and an external sliding tube. Due to the external tube sliding, the device transforms between flexible and rigid states. By transporting the device into the liposome, the conformational change of the origami device induces a structural change in the liposome. The results obtained demonstrate that the programmed DNA origami device can be applied to regulate the microcosmic structural rigidity of liposomes. Because microcosmic structural rigidity is important to cell proliferation and function, the results obtained potentially provide a foundation for the regulation of cell microcosmic structural rigidity using DNA nanostructures.     

DNA Origami Catenanes Templated by Gold Nanoparticles

Mechanically interlocked molecules have marked a breakthrough in the field of topological chemistry and boosted the vigorous development of molecular machinery. As an archetypal example of the interlocked molecules, catenanes comprise macrocycles that are threaded through one another like links in a chain. Inspired by the transition metal–templated approach of catenanes synthesis, the hierarchical assembly of DNA origami catenanes templated by gold nanoparticles is demonstrated in this work. DNA origami catenanes, which contain two, three or four interlocked rings are successfully created. In particular, the origami rings within the individual catenanes can be set free with respect to one another by releasing the interconnecting gold nanoparticles. This work will set the basis for rich progress toward DNA‐based molecular architectures with unique structural programmability and well‐defined topology.     

Design, assembly, and activity of antisense DNA nanostructures

Discrete DNA nanostructures allow simultaneous features not possible with traditional DNA forms: encapsulation of cargo, display of multiple ligands, and resistance to enzymatic digestion. These properties suggested using DNA nanostructures as a delivery platform. Here, DNA pyramids displaying antisense motifs are shown to be able to specifically degrade mRNA and inhibit protein expression in vitro, and they show improved cell uptake and gene silencing when compared to linear DNA. Furthermore, the activity of these pyramids can be regulated by the introduction of an appropriate complementary strand. These results highlight the versatility of DNA nanostructures as functional devices.     

Design and Analysis of Localized DNA Hybridization Chain Reactions

Theoretical models of localized DNA hybridization reactions on nanoscale substrates indicate potential benefits over conventional DNA hybridization reactions. Recently, a few approaches have been proposed to speed‐up DNA hybridization reactions; however, experimental confirmation and quantification of the acceleration factor have been lacking. Here, a system to investigate localized DNA hybridization reactions on a nanoscale substrate is presented. The system consists of six metastable DNA hairpins that are tethered to a long DNA track. The localized DNA hybridization reaction of the proposed system is triggered by a DNA strand which initiates the subsequent self‐assembly. Fluorescence kinetics indicates that the half‐time completion of a localized DNA hybridization chain reaction is six times faster than the same reaction in the absence of the substrate. The proposed system provides one of the first known quantification of the speed‐up of DNA hybridization reactions due to the locality effect.     

Encapsulation of Gold Nanoparticles into DNA Minimal Cages for 3D‐Anisotropic Functionalization and Assembly

Gold nanoparticles (AuNPs) endowed with anisotropic DNA valency are an important class of materials, as they can assemble into complex structures with a minimal number of DNA strands. However, methods to encode 3D DNA strand patterns on AuNPs with a controlled number of unique DNA strands in a predesigned spatial arrangement remain elusive. In this work, a simple one‐step method to yield such DNA‐decorated AuNPs is demonstrated, through encapsulating AuNPs into DNA minimal nanocages. The AuNP@DNA cage encapsulation complex inherits the 3D anisotropic molecular information from the DNA nanocage with enhanced structural stability. The DNA nanocage can be further functionalized and used as a building block for the self‐assembly of complex architectures, such as dimers and trimers, programmed assemblies with sequential growth DNA backbones and DNA origami.     

A Self‐Assembled DNA Origami‐Gold Nanorod Complex for Cancer Theranostics

A self‐assembled DNA origami (DO)‐gold nanorod (GNR) complex, which is a dual‐functional nanotheranostics constructed by decorating GNRs onto the surface of DNA origami, is demonstrated. After 24 h incubation of two structured DO‐GNR complexes with human MCF7 breast cancer cells, significant enhancement of cell uptake is achieved compared to bare GNRs by two‐photon luminescence imaging. Particularly, the triangle shaped DO‐GNR complex exhibits optimal cellular accumulation. Compared to GNRs, improved photothermolysis against tumor cells is accomplished for the triangle DO‐GNR complex by two‐photon laser or NIR laser irradiation. Moreover, the DO‐GNR complex exhibits enhanced antitumor efficacy compared with bare GNRs in nude mice bearing breast tumor xenografts. The results demonstrate that the DO‐GNR complex can achieve optimal two‐photon cell imaging and photothermal effect, suggesting a promising candidate for cancer diagnosis and therapy both in vitro and in vivo.