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.