Zhongqiang Yang

Self-assembled DNA hydrogels with designable thermal and enzymatic responsiveness.

or used as a programmable template to direct the assembly of nanoparticles. [ 14–17 ] Recently, the concept of DNA assembly has been expanded to construct “DNA hydrogels”, which are crosslinked networks swollen in an aqueous phase. [ 18–31 ] Though hydrogels have great potential in biological and medical applications, [ 32–36 ] such as drug and gene delivery, biosensing, and tissue engineering, studying the preparation of DNA hydrogels with designable properties is still in its early stages. In the past, several methods have been reported to prepare DNA hydrogels, for example, DNA directly extracted from the nucleus in nature, behaves like a long linear polymer and forms a hydrogel via physical entanglement or by chemical crosslinking of small molecules. [ 18 − 20] Similarly, DNA can be used as a negatively charged polymer and form a complex with cationic (poly)electrolytes through electrostatic interactions. [ 21 , 22 ] However, both methods treated DNA as a polymer and did not take advantage of the self-assembly of DNA into ordered structures, therefore, the resulting hydrogels lacked precise structural control and specifi c responses. Instead of using physical interactions, DNA can be covalently grafted onto synthetic polymers and serve as a cross-linker, the recognition of complementary DNA strands leads to crosslinking of polymer chains and causes hydrogel formation. [ 23 − 28] In general, the preparation of a DNA-polymer hybrid requires laborious modifi cation steps, and an easy and fast strategy to build tailored DNA hydrogels is desired. Luo and his coworkers have developed a new approach to construct

DNA nanotechnology based on i-motif structures.

CONSPECTUS: Most biological processes happen at the nanometer scale, and understanding the energy transformations and material transportation mechanisms within living organisms has proved challenging. To better understand the secrets of life, researchers have investigated artificial molecular motors and devices over the past decade because such systems can mimic certain biological processes. DNA nanotechnology based on i-motif structures is one system that has played an important role in these investigations. In this Account, we summarize recent advances in functional DNA nanotechnology based on i-motif structures. The i-motif is a DNA quadruplex that occurs as four stretches of cytosine repeat sequences form C·CH(+) base pairs, and their stabilization requires slightly acidic conditions. This unique property has produced the first DNA molecular motor driven by pH changes. The motor is reliable, and studies show that it is capable of millisecond running speeds, comparable to the speed of natural protein motors. With careful design, the output of these types of motors was combined to drive micrometer-sized cantilevers bend. Using established DNA nanostructure assembly and functionalization methods, researchers can easily integrate the motor within other DNA assembled structures and functional units, producing DNA molecular devices with new functions such as suprahydrophobic/suprahydrophilic smart surfaces that switch, intelligent nanopores triggered by pH changes, molecular logic gates, and DNA nanosprings. Recently, researchers have produced motors driven by light and electricity, which have allowed DNA motors to be integrated within silicon-based nanodevices. Moreover, some devices based on i-motif structures have proven useful for investigating processes within living cells. The pH-responsiveness of the i-motif structure also provides a way to control the stepwise assembly of DNA nanostructures. In addition, because of the stability of the i-motif, this structure can serve as the stem of one-dimensional nanowires, and a four-strand stem can provide a new basis for three-dimensional DNA structures such as pillars. By sacrificing some accuracy in assembly, we used these properties to prepare the first fast-responding pure DNA supramolecular hydrogel. This hydrogel does not swell and cannot encapsulate small molecules. These unique properties could lead to new developments in smart materials based on DNA assembly and support important applications in fields such as tissue engineering. We expect that DNA nanotechnology will continue to develop rapidly. At a fundamental level, further studies should lead to greater understanding of the energy transformation and material transportation mechanisms at the nanometer scale. In terms of applications, we expect that many of these elegant molecular devices will soon be used in vivo. These further studies could demonstrate the power of DNA nanotechnology in biology, material science, chemistry, and physics.

Rapid Formation of a Supramolecular Polypeptide–DNA Hydrogel for In Situ Three‐Dimensional Multilayer Bioprinting

A rapidly formed supramolecular polypeptide-DNA hydrogel was prepared and used for in situ multilayer three-dimensional bioprinting for the first time. By alternative deposition of two complementary bio-inks, designed structures can be printed. Based on their healing properties and high mechanical strengths, the printed structures are geometrically uniform without boundaries and can keep their shapes up to the millimeter scale without collapse. 3D cell printing was demonstrated to fabricate live-cell-containing structures with normal cellular functions. Together with the unique properties of biocompatibility, permeability, and biodegradability, the hydrogel becomes an ideal biomaterial for 3D bioprinting to produce designable 3D constructs for applications in tissue engineering.

Improving the yield of mono-DNA-functionalized gold nanoparticles through dual steric hindrance.

A novel strategy of dual steric hindrance, which was obtained by Janus modification of gold nanoparticles (Au NPs) and volume exclusion of DNA, was adopted to prepare mono-DNA-modified Au NPs. The yield of mono-DNA-functionalized Au NPs significantly improved from 44 to 70% in the reaction between Au NPs and thiolated DNA. Furthermore, the specificity of mono-DNA-functionalized Au NPs was enhanced from 57 to 95%. The as-prepared Au NPs without postsynthetic treatment showed good controllability in self-assembly fabrication of complex nanostructures.

Responsive Double Network Hydrogels of Interpenetrating DNA and CB[8] Host–Guest Supramolecular Systems

A supramolecular double network hydrogel is presented by physical interpenetration of DNA and cucurbit[8]uril networks. In addition to exhibiting an increase in strength and thermal stability, the double network hydrogel possesses excellent properties such as stretchability, ductility, shear-thinning, and thixotropy. Moreover, it is enzymatically responsive to both nuclease and cellulase, as well as small molecules, showing great potential as a new soft material scaffold.

Regulation of an Enzyme Cascade Reaction by a DNA Machine

A strategy for the regulation of enzyme cascade reaction efficiency by a DNA machine in vitro is presented. Two cascade enzymes (GOx and HRP) are attached to the DNA machine, and the enzyme cascade reaction shows much higher efficiency when the two enzymes are brought closer by the DNA machine than when they are distant.

Efficient, pH‐Triggered Drug Delivery Using a pH‐Responsive DNA‐Conjugated Gold Nanoparticle

A stable, efficient drug nanocarrier that resists non-specific adsorption of serum proteins has been developed using a PEG750-modified pH-responsive DNA-gold nanoparticle conjugate. It provides efficient delivery and pH-triggered release of anticancer drugs into cancer cells, leading to high cytotoxicity.

pH‐Responsive Size‐Tunable Self‐Assembled DNA Dendrimers

Putting the DNA in dendrimers: a strategy to swiftly prepare DNA dendrimers based solely on DNA self-assembly is presented. This technique produces highly pure DNA dendrimers with an excellent yield of high generation dendrimers. The incorporation of molecular motors (i-motifs) into the DNA dendrimers allows for a change in size (up to 30%) in response to changing pH values.

A Triggered DNA Hydrogel Cover to Envelop and Release Single Cells

We develop an enzyme-triggered permeable DNA hydrogel cover to envelop and release single cells in microwells. The porous structure of the DNA hydrogel allows nutrients and waste to pass through, leading to a cell viability as high as 98%. The design provides a general method to culture, monitor, and manipulate single cells, and has potential applications in cell patterning and studying cell communication.

Frame‐Guided Assembly of Vesicles with Programmed Geometry and Dimensions

In molecular self-assembly molecules form organized structures or patterns. The control of the self-assembly process is an important and challenging topic. Inspired by the cytoskeletal-membrane protein lipid bilayer system that determines the shape of eukaryotic cells, we developed a frame-guided assembly process as a general strategy to prepare heterovesicles with programmed geometry and dimensions. This method offers greater control over self-assembly which may benefit the understanding of the formation mechanism as well as the functions of the cell membrane.