Zhen-Gang Wang

DNA origami as a carrier for circumvention of drug resistance.

Although a multitude of promising anti-cancer drugs have been developed over the past 50 years, effective delivery of the drugs to diseased cells remains a challenge. Recently, nanoparticles have been used as drug delivery vehicles due to their high delivery efficiencies and the possibility to circumvent cellular drug resistance. However, the lack of biocompatibility and inability to engineer spatially addressable surfaces for multi-functional activity remains an obstacle to their widespread use. Here we present a novel drug carrier system based on self-assembled, spatially addressable DNA origami nanostructures that confronts these limitations. Doxorubicin, a well-known anti-cancer drug, was non-covalently attached to DNA origami nanostructures through intercalation. A high level of drug loading efficiency was achieved, and the complex exhibited prominent cytotoxicity not only to regular human breast adenocarcinoma cancer cells (MCF 7), but more importantly to doxorubicin-resistant cancer cells, inducing a remarkable reversal of phenotype resistance. With the DNA origami drug delivery vehicles, the cellular internalization of doxorubicin was increased, which contributed to the significant enhancement of cell-killing activity to doxorubicin-resistant MCF 7 cells. Presumably, the activity of doxorubicin-loaded DNA origami inhibits lysosomal acidification, resulting in cellular redistribution of the drug to action sites. Our results suggest that DNA origami has immense potential as an efficient, biocompatible drug carrier and delivery vehicle in the treatment of cancer.

Rolling Up Gold Nanoparticle-Dressed DNA Origami into Three-Dimensional Plasmonic Chiral Nanostructures

Construction of three-dimensional (3D) plasmonic architectures using structural DNA nanotechnology is an emerging multidisciplinary area of research. This technology excels in controlling spatial addressability at sub-10 nm resolution, which has thus far been beyond the reach of traditional top-down techniques. In this paper, we demonstrate the realization of 3D plasmonic chiral nanostructures through programmable transformation of gold nanoparticle (AuNP)-dressed DNA origami. AuNPs were assembled along two linear chains on a two-dimensional rectangular DNA origami sheet with well-controlled positions and particle spacing. By rational rolling of the 2D origami template, the AuNPs can be automatically arranged in a helical geometry, suggesting the possibility of achieving engineerable chiral nanomaterials in the visible range.

Visualization of the intracellular location and stability of DNA origami with a label-free fluorescent probe

We report a label-free fluorescent strategy to study the distribution and stability of DNA origami nanostructures in live, cellular systems, using carbazole-based biscyanine as a probe molecule which has the characteristic property of restriction of intramolecular rotation (RIR) induced emission.

Engineering DNA Self-Assemblies as Templates for Functional Nanostructures

CONSPECTUS: DNA is a well-known natural molecule that carries genetic information. In recent decades, DNA has been used beyond its genetic role as a building block for the construction of engineering materials. Many strategies, such as tile assembly, scaffolded origami and DNA bricks, have been developed to design and produce 1D, 2D, and 3D architectures with sophisticated morphologies. Moreover, the spatial addressability of DNA nanostructures and sequence-dependent recognition enable functional elements to be precisely positioned and allow for the control of chemical and biochemical processes. The spatial arrangement of heterogeneous components using DNA nanostructures as the templates will aid in the fabrication of functional materials that are difficult to produce using other methods and can address scientific and technical challenges in interdisciplinary research. For example, plasmonic nanoparticles can be assembled into well-defined configurations with high resolution limit while exhibiting desirable collective behaviors, such as near-field enhancement. Conducting metallic or polymer patterns can be synthesized site-specifically on DNA nanostructures to form various controllable geometries, which could be used for electronic nanodevices. Biomolecules can be arranged into organized networks to perform programmable biological functionalities, such as distance-dependent enzyme-cascade activities. DNA nanostructures can carry multiple cytoactive molecules and cell-targeting groups simultaneously to address medical issues such as targeted therapy and combined administration. In this Account, we describe recent advances in the functionalization of DNA nanostructures in different fashions based on our research efforts in nanophotonics, nanoelectronics, and nanomedicine. We show that DNA origami nanostructures can guide the assembly of achiral, spherical, metallic nanoparticles into nature-mimicking chiral geometries through hybridization between complementary DNA strands on the surface of nanoparticles and DNA scaffolds, to generate circular dichroism (CD) response in the visible light region. We also show that DNA nanostructures, on which a HRP-mimicking DNAzyme acts as the catalyst, can direct the site-selective growth of conductive polymer nanomaterials with template configuration-dependent doping behaviors. We demonstrate that DNA origami nanostructures can act as an anticancer-drug carrier, loading drug through intercalation, and can effectively circumvent the drug resistance of cultured cancer cells. Finally, we show a label-free strategy for probing the location and stability of DNA origami nanocarriers in cellular environments by docking turn-off fluorescence dyes in DNA double helices. These functionalizations require further improvement and expansion for realistic applications. We discuss the future opportunities and challenges of DNA based assemblies. We expect that DNA nanostructures as engineering materials will stimulate the development of multidisciplinary and interdisciplinary research.

Self-Assembled Catalytic DNA Nanostructures for Synthesis of Para-directed Polyaniline

Templated synthesis has been considered as an efficient approach to produce polyaniline (PANI) nanostructures. The features of DNA molecules enable a DNA template to be an intriguing template for fabrication of emeraldine PANI. In this work, we assembled HRP-mimicking DNAzyme with different artificial DNA nanostructures, aiming to manipulate the molecular structures and morphologies of PANI nanostructures through the controlled DNA self-assembly. UV-vis absorption spectra were used to investigate the molecular structures of PANI and monitor kinetic growth of PANI. It was found that PANI was well-doped at neutral pH and the redox behaviors of the resultant PANI were dependent on the charge density of the template, which was controlled by the template configurations. CD spectra indicated that the PANI threaded tightly around the helical DNA backbone, resulting in the right handedness of PANI. These reveal the formation of the emeraldine form of PANI that was doped by the DNA. The morphologies of the resultant PANI were studied by AFM and SEM. It was concluded from the imaging and spectroscopic kinetic results that PANI grew preferably from the DNAzyme sites and then expanded over the template to form 1D PANI nanostructures. The strategy of the DNAzyme-DNA template assembly brings several advantages in the synthesis of para-coupling PANI, including the region-selective growth of PANI, facilitating the formation of a para-coupling structure and facile regulation. We believe this study contributes significantly to the fabrication of doped PANI nanopatterns with controlled complexity, and the development of DNA nanotechnology.

Engineering the pH-Responsive Catalytic Behavior of AuNPs by DNA

Noble metal nanoparticles have attracted much interest in the heterogeneous catalysis. Particularly, efficient manipulation of the responsive catalytic properties of the metal nanoparticles is an interesting topic. In this work, a simple and efficient strategy is developed to regulate the pH-responsive catalytic activities of glucose oxidase (GOx)-mimicking gold nanoparticles (AuNPs). Four DNA strands (regulating strands) that differ slightly in sequences are used to interact non-covalently with citrate-capped AuNPs, resulting in markedly distinct pH-dependent catalytic behavior of AuNPs. This is ascribed to the characteristic pH-induced conformational change of the DNA strands that leads to the different adsorption capability to the NPs surface, as demonstrated by pH-CD profiles of the respective DNA molecules. The pH-dependent catalysis of AuNPs is also encoded with structural information of the double-stranded DNA (including regulating strands and their complementary strands) that has conformation resistant or responsive to pH change. As a result, the catalysis can be programmed into an AND gate, a XNOR gate or a NOT gate, using pH and complementary strand as the inputs, the nanoparticle activity as the output and the regulating strands as the programs. This work can be expanded by engineering the catalytic behavior of noble metal nanoparticles to respond smartly to a variety of environmental stimuli, such as metal ions or light wavelengths. These results may provide insight into understanding ligand-regulated nanometallic catalysis.

DNA‐Based Self‐Assembly for Functional Nanomaterials

The unprecedented development of DNA nanotechnology has caused DNA self-assembly to attract close attention in many disciplines. In this research news article, the employment of DNA self-assembly in the fields of materials science and nanotechnology is described. DNA self-assembly can be used to prepare bulk-scale hydrogels and 3D macroscopic crystals with nanoscale internal structures, to induce the crystallization of nanoparticles, to template the fabrication of organic conductive nanomaterials, and to act as drug delivery vehicles for therapeutic agents. The properties and functions are fully tunable because of the designability and specificity of DNA assembly. Moreover, because of the intrinsic dynamics, DNA self-assembly can act as a program switch and can efficiently control stimuli responsiveness. We highlight the power of DNA self-assembly in the preparation and function regulation of materials, aiming to motivate future multidisciplinary and interdisciplinary research. Finally, we describe some of the challenges currently faced by DNA assembly that may affect the functional evolution of such materials, and we provide our insights into the future directions of several DNA self-assembly-based nanomaterials.

Functional DNA nanostructures for photonic and biomedical applications.

DNA nanostructures, especially DNA origami, receive close interest because of the programmable control over their shape and size, precise spatial addressability, easy and high-yield preparation, mechanical flexibility, and biocompatibility. They have been used to organize a variety of nanoscale elements for specific functions, resulting in unprecedented improvements in the field of nanophotonics and nanomedical research. In this review, the discussion focuses on the employment of DNA nanostructures for the precise organization of noble metal nanoparticles to build interesting plasmonic nanoarchitectures, for the fabrication of visualized sensors and for targeted drug delivery. The effects offered by DNA nanostructures are highlighted in the areas of nanoantennas, collective plasmonic behaviors, single-molecule analysis, and cancer-cell targeting or killing. Finally, the challenges in the field of DNA nanotechnology for realistic application are discussed and insights for future directions are provided.

A facile and efficient method to modify gold nanorods with thiolated DNA at a low pH value.

We report a simple, rapid and efficient strategy for modification of gold nanorods (AuNRs) with thiolated DNA at low solution pH and high salt concentration. DNA functionalized AuNRs were then used to assemble with DNA modified gold nanoparticles to form discrete satellite nanostructures.

Smart Nanomachines Based on DNA Self-Assembly

DNA-based nanomachines are self-assembled DNA superstructures that harness chemical free energy to perform mechanical work. The development of DNA machines has benefited greatly from the achievements in both structural and dynamic DNA nanotechnology. In this review, the configurations of DNA machines, fuel systems, and operations are discussed to outline the evolving paths of DNA machines. The focus is on the smart mechanical behavior of DNA machines, from the standpoint of upgrading the complexity of DNA nanostructures, cooperative activation of multimachinary systems, and the establishment of a network of the mechanical states. In the end, the challenges are highlighted and possible solutions are proposed to push forward smart DNA nanomachines, with the goal of creating biomimicking systems. Insights are also provided into the potential applications of the DNA machines with designable intelligence.