DNA Nanocarriers: Programmed to Deliver Madhanagopal, Bharath Raj; Zhang, Shunqing; Demirel, Esra ...
Trends in biochemical sciences (Amsterdam. Regular ed.),
December 2018, 2018-12-00, Letnik:
43, Številka:
12
Journal Article
Recenzirano
Simple base-pairing rules of complementarity, perfected by evolution for encoding genetic information, provide unprecedented control over the process of DNA self-assembly. These rules allow us to ...build exquisite nanostructures and rationally design their morphology, fine-tune their chemical properties, and program their response to environmental stimuli. DNA nanostructures have emerged as promising candidates for transporting drugs across various physiological barriers of the body. In this review, we discuss the strategies used to transform DNA nanostructures into drug delivery vehicles. We provide an overview of recent attempts at using them to deliver small molecule drugs and macromolecular cargoes and present the challenges that lay ahead for these synthetic vectors as they set new paradigms in the field of nanotechnology and medicine.
DNA can be used as a building block for creating nanoscale structures.
DNA nanostructures are programmable, offering unique characteristics for use as drug delivery carriers.
DNA nanocarriers can be targeted to specific cells; be triggered using chemical, molecular or environment cues to release drugs; and offer tunable cellular uptake profiles.
DNA nanocarriers are used for a variety of cargos including small molecules, therapeutic oligonucleotides, antibodies, peptides, and photosensitizers.
Nanocarriers can be functionalized to provide a ‘see-and-treat’ strategy for the creation of theranostics.
The spatial organization of metal nanoparticles has become an important tool for manipulating light in nanophotonic applications. Silver nanoparticles, particularly silver nanorods, have excellent ...plasmonic properties but are prone to oxidation and are therefore inherently unstable in aqueous solutions and salt-containing buffers. Consequently, gold nanoparticles have often been favored, despite their inferior optical performance. Bimetallic, i.e., gold–silver core–shell nanoparticles, can resolve this issue. We present a method for synthesizing highly stable gold–silver core–shell NRs that are instantaneously functionalized with DNA, enabling chiral self-assembly on DNA origami. The silver shell gives rise to an enhancement of plasmonic properties, reflected here in strongly increased circular dichroism, as compared to pristine gold nanorods. Gold–silver nanorods are ideal candidates for plasmonic sensing with increased sensitivity as needed in pathogen RNA or antibody testing for nonlinear optics and light-funneling applications in surface enhanced Raman spectroscopy. Furthermore, the control of interparticle orientation enables the study of plasmonic phenomena, in particular, synergistic effects arising from plasmonic coupling of such bimetallic systems.
DNA has become a prime material for assembling complex three‐dimensional objects that promise utility in various areas of application. However, achieving user‐defined goals with DNA objects has been ...hampered by the difficulty to prepare them at arbitrary concentrations and in user‐defined solution conditions. Here, we describe a method that solves this problem. The method is based on poly(ethylene glycol)‐induced depletion of species with high molecular weight. We demonstrate that our method is applicable to a wide spectrum of DNA shapes and that it achieves excellent recovery yields of target objects up to 97 %, while providing efficient separation from non‐integrated DNA strands. DNA objects may be prepared at concentrations up to the limit of solubility, including the possibility for bringing DNA objects into a solid phase. Due to the fidelity and simplicity of our method we anticipate that it will help to catalyze the development of new types of applications that use self‐assembled DNA objects.
PEG packs them all: A depletion‐based method is used for the preparation of self‐assembled megadalton‐scale DNA objects up to the limit of solubility, including the possibility for bringing such objects into a solid phase. Due to its fidelity and simplicity this method might benefit the development of new types of applications that use self‐assembled DNA objects.
DNA origami is a powerful approach for assembling plasmonic nanoparticle dimers and Raman dyes with high yields and excellent positioning control. Here we show how optothermal-induced shrinking of a ...DNA origami template can be employed to control the gap sizes between two 40 nm gold nanoparticles in a range from 1 to 2 nm. The high field confinement achieved with this optothermal approach was demonstrated by detection of surface-enhanced Raman spectroscopy (SERS) signals from single molecules that are precisely placed within the DNA origami template that spans the nanoparticle gap. By comparing the SERS intensity with respect to the field enhancement in the plasmonic hot-spot region, we found good agreement between measurement and theory. Our straightforward approach for the fabrication of addressable plasmonic nanosensors by DNA origami demonstrates a path toward future sensing applications with single-molecule resolution.
The nanoscale spatial organization of transmembrane tumor necrosis factor (TNF) receptors has been implicated in the regulation of cellular fate. Accordingly, molecular tools that can induce specific ...arrangements of these receptors on cell surfaces would give us an opportunity to study these effects in detail. To achieve this, we introduce DNA origami nanostructures that precisely scaffold the patterning of TNF-related apoptosis-inducing ligand-mimicking peptides at nanoscale level. Stimulating human breast cancer cells with these patterns, we find that around 5 nm is the critical interligand distance of hexagonally patterned peptides to induce death receptor clustering and a resulting apoptosis. We thus offer a strategy to reverse the non-efficacy of current ligand- and antibody-based methods for TNF superfamily activation.
Self-assembly processes, while promising for enabling the fabrication of complexly organized nanomaterials from nanoparticles, are often limited in creating structures with multiscale order. These ...limitations are due to difficulties in practically realizing the assembly processes required to achieve such complex organizations. For a long time, a hierarchical assembly attracted interest as a potentially powerful approach. However, due to the experimental limitations, intermediate-level structures are often heterogeneous in composition and structure, which significantly impacts the formation of large-scale organizations. Here, we introduce a two-stage assembly strategy: DNA origami frames scaffold a coordination of nanoparticles into designed 3D nanoclusters, and then these clusters are assembled into ordered lattices whose types are determined by the clusters’ valence. Through modulating the nanocluster architectures and intercluster bindings, we demonstrate the successful formation of complexly organized nanoparticle crystals. The presented two-stage assembly method provides a powerful fabrication strategy for creating nanoparticle superlattices with prescribed unit cells.
With the introduction of the DNA origami technique, it became possible to rapidly synthesize almost arbitrarily shaped molecular nanostructures at nearly stoichiometric yields. The technique ...furthermore provides absolute addressability in the sub-nm range, rendering DNA origami nanostructures highly attractive substrates for the controlled arrangement of functional species such as proteins, dyes, and nanoparticles. Consequently, DNAorigami nanostructures have found applications in numerous areas of fundamental and applied research, ranging from drug delivery to biosensing to plasmonics to inorganic materials synthesis. Since many of those applications rely on structurally intact, well-definedDNA origami shapes, the issue of DNA origami stability under numerous application-relevant environmental conditions has received increasing interest in the past few years. In this mini-review we discuss the structural stability, denaturation, and degradation of DNA origami nanostructures under different conditions relevant to the fields of biophysics and biochemistry, biomedicine, and materials science, and the methods to improve their stability for desired applications.
Display omitted
The bacterial flagellar motor is a rotary machine composed of functional modular components, which can perform bidirectional rotations to control the migration behavior of the bacterial cell. It ...resembles a two-cogwheel gear system, which consists of small and large cogwheels with cogs at the edges to regulate rotations. Such gearset models provide elegant blueprints to design and build artificial nanomachinery with desired functionalities. In this work, we demonstrate DNA assembly of a structurally well-defined nanodevice, which can carry out programmable rotations powered by DNA fuels. Our rotary nanodevice consists of three modular components, small origami ring, large origami ring, and gold nanoparticles (AuNPs). They mimic the sun gear, ring gear, and planet gears in a planetary gearset accordingly. These modular components are self-assembled in a compact manner, such that they can work cooperatively to impart bidirectional rotations. The rotary dynamics is optically recorded using fluorescence spectroscopy in real time, given the sensitive distance-dependent interactions between the tethered fluorophores and AuNPs on the rings. The experimental results are well supported by the theoretical calculations.
PDF
