G‐Quadruplex‐Mediated Molecular Switching of Self‐Assembled 3D DNA Nanocages

Abstract

We demonstrated as trategy to reversibly extend and contract 3D DNA nanocages based on G-rich DNA strandsa ss caffolds in the presence of K + or chelating agents. The contraction and extension of nanocage would be regulated by formation and deformationo fGquadruplexi nt he presence of K + ions and chelating agents, respectively.C ompared to single telomeric DNA strands, self-assembled 3D DNA nanocages integrated with three HTLs act as horseradish peroxidase mimicking DNAzymesf or colorimetric detectiona nd monitoring of cholesterol with high stability towardn uclease and blood serum degradations. This is the first example of facile construction of 3D DNA nanostructures with contractile, reversible, and catalytic features based on the assembly and disassembly of G-quadruplexes. This work offers an ew platform for manipulation of nanoscale conformational changes and as tep forwardi no btaining stimuli-responsive 3D DNA nanomaterials with versatile reactivity and functionalities.The base sequence of oligonucleotides, which encodes substantialf unctional and structural information, facilitates the rational design of stimuli-responsive materials.[1] Guanine-rich nucleic acids exhibit not only specificb inding capabilities to various targets including metal ions, [2] proteins [3] or small molecules, [4] but also reversible catalytic functions in the form of hemin/G-quadruplexc omplexes. [5][6][7] The catalytically inactive, random-coil structure of guanine-rich DNA reversibly switches into ac atalytically active G-quadruplex by corresponding input, [8] enablingi ts structuralr econfigurationa nd promoting its applicationsi ns ensing, [3,4,9,10] analytical biochemistry, [11] molecular biology, [12] biomedicine [13] and logic gate development.[14] This G-rich, non-Watson-Crick base-paired building block has been increasingly encoded in self-assembled DNA nanostructures to generate stimuli-responsivet wo dimensional DNA networks [15][16][17] and long DNA nanowires.[18] So far,t he use of G-quadruplex-functionalized 3D DNA nanostructures for structuralr econfiguration is highly limited. Not surprisingly,3 D DNA nanostructures capable of molecular switching play an important role because of their potentialapplications in molecular sensing, drug delivery,m iniaturized robotics and dynamic nanomaterials.[19] Different strategies including addition of specific DNA strands, [20,21] small molecules, [22] protons, [23] enzymes [24] or photons [25] have been used to control the 3D movement in terms of shapes and sizes. Inspired by the reversible conformational switching properties of the G-rich nucleic acids under appropriate conditions, the exploration of stimuliresponsive G-quadruplex-containing 3D DNA nanomaterials with increasing patterns of molecular diversity,c omplexity,a nd functions is still ac hallenge.Herein, we report on the reversible conformationalc hange of 3D DNA nanocages that allows switchable turn ON and OFF of their optical signals. The contraction and extension of HT-NC can be regulated by formation...

Nucleic Acids and Their Analogues for Biomedical Applications

“…G-rich strands can be stabilized into G-quadruplexes in the presence of metal ions. For example, our group reported a strategy to extend and contract DNA nanocages based on G-rich strands [ 201 ]. The contraction and extension of these developed DNA nanocages can be regulated via the reversible formation and deformation of G-quadruplex in the presence of K + ions and chelating agents.…”

Photoresponsive Self‐Assembled DNA Nanomaterials: Design, Working Principles, and Applications

“…High programmability and predictability of oligonucleotides have instigated the rapid development in the field of 2D and 3D DNA self‐assembly for potential applications in materials science, biology, physics, and engineering . In fact, the base sequences of oligonucleotide, for example, cytosine‐rich DNA, guanosine‐rich DNA, and aptamers encode valuable functional and structural information, being favorable for the rational design of stimuli‐responsive DNA nanomaterials . In the past years, a large number of static and dynamic self‐assembled DNA nanostructures have been successfully designed and synthesized via different self‐assembly strategies.…”

Facile construction of a DNA tetrahedron in unconventional ladder-like arrangements at room temperature

“…1,2 These nanostructures have been used for in vitro applications such as nanotools for molecular biology, biosensors, and smart nanodevices. [3][4][5] Due to their excellent biocompatibility and cellular permeability, they have become a promising platform for drug delivery applications. 6,7 As the most classical and simplest three-dimensional (3D) structure, a DNA tetrahedron can be synthesized by mixing four singlestranded DNAs in one-pot aer a quick thermal annealing process.…”

“…12 Alternatively, an origami-based assembly has been applied to hybridize the DNA scaffold and staple strands to result in planar triangular faces; this is followed by the closing of each of the faces to form a DNA tetrahedron. 13 Due to the substantial number of strands used in this approach, this method suffers from high production cost and also results in a very large and rigid DNA tetrahedron, 14 for example, cages with 54 nm edges and an internal cavity with a volume of 15 000 nm 3 . 15 On the other hand, this origami approach is highly limited to the construction of very small sized 3D nanostructures.…”