Nucleic acid-functionalized polyacrylamide chains that are cooperatively cross-linked by i-motif and nucleic acid duplex units yield, at pH 5.0, DNA hydrogels exhibiting shape-memory properties. Separation of the i-motif units at pH 8.0 dissolves the hydrogel into a quasi-liquid phase. The residual duplex units provide, however, a memory code in the quasi-liquid allowing the regeneration of the hydrogel shape at pH 5.0.

Triplex nucleic acids have recently attracted interest as part of the rich "toolbox" of structures used to develop DNA-based nanostructures and materials. This Review addresses the use of DNA triplexes to assemble sensing platforms and molecular switches. Furthermore, the pH-induced, switchable assembly and dissociation of triplex-DNA-bridged nanostructures are presented. Specifically, the aggregation/deaggregation of nanoparticles, the reversible oligomerization of origami tiles and DNA circles, and the use of triplex DNA structures as functional units for the assembly of pH-responsive systems and materials are described. Examples include semiconductor-loaded DNA-stabilized microcapsules, DNA-functionalized dye-loaded metal-organic frameworks (MOFs), and the pH-induced release of the loads. Furthermore, the design of stimuli-responsive DNA-based hydrogels undergoing reversible pH-induced hydrogel-to-solution transitions using triplex nucleic acids is introduced, and the use of triplex DNA to assemble shape-memory hydrogels is discussed. An outlook for possible future applications of triplex nucleic acids is also provided.

The synthesis of doxorubicin‐loaded metal–organic framework nanoparticles (NMOFs) coated with a stimuli‐responsive nucleic acid‐based polyacrylamide hydrogel is described. The formation of the hydrogel is stimulated by the crosslinking of two polyacrylamide chains, PA and PB, that are functionalized with two nucleic acid hairpins (4) and (5) using the strand‐induced hybridization chain reaction. The resulting duplex‐bridged polyacrylamide hydrogel includes the anti‐ATP (adenosine triphosphate) aptamer sequence in a caged configuration. The drug encapsulated in the NMOFs is locked by the hydrogel coating. In the presence of ATP that is overexpressed in cancer cells, the hydrogel coating is degraded via the formation of the ATP–aptamer complex, resulting in the release of doxorubicin drug. In addition to the introduction of a general means to synthesize drug‐loaded stimuli‐responsive nucleic acid‐based polyacrylamide hydrogel‐coated NMOFs hybrids, the functionalized NMOFs resolve significant limitations associated with the recently reported nucleic acid‐gated drug‐loaded NMOFs. The study reveals substantially higher loading of the drug in the hydrogel‐coated NMOFs as compared to the nucleic acid‐gated NMOFs and overcomes the nonspecific leakage of the drug observed with the nucleic‐acid‐protected NMOFs. The doxorubicin‐loaded, ATP‐responsive, hydrogel‐coated NMOFs reveal selective and effective cytotoxicity toward MDA‐MB‐231 breast cancer cells, as compared to normal MCF‐10A epithelial breast cells.

Drug-loaded DNA-capped metal–organic framework nanoparticles are unlocked by pH or Mg2+ ions/ATP triggers, resulting in the release of the loads.

A novel method to assemble acrylamide/acrydite DNA copolymer hydrogels on surfaces, specifically gold-coated surfaces, is introduced. The method involves the synthesis of two different copolymer chains consisting of hairpin A, HA, modified acrylamide copolymer and hairpin B, HB, acrylamide copolymer. In the presence of a nucleic acid promoter monolayer associated with the surface, the hybridization chain reaction between the two hairpin-modified polymer chains is initiated, giving rise to the cross-opening of hairpins HA and HB and the formation of a cross-linked hydrogel on the surface. By the cofunctionalization of the HA- and HB-modified polymer chains with G-rich DNA tethers that include the G-quadruplex subunits, hydrogels of switchable stiffness are generated. In the presence of K(+)-ions, the hydrogel associated with the surface is cooperatively cross-linked by duplex units of HA and HB, and K(+)-ion-stabilized G-quadruplex units, giving rise to a stiff hydrogel. The 18-crown-6-ether-stimulated elimination of the K(+)-ions dissociates the bridging G-quadruplex units, resulting in a hydrogel of reduced stiffness. The duplex/G-quadruplex cooperatively stabilized hydrogel associated with the surface reveals switchable electrocatalytic properties. The incorporation of hemin into the G-quadruplex units electrocatalyzes the reduction of H2O2. The 18-crown-6-ether stimulated dissociation of the hemin/G-quadruplex bridging units leads to a catalytically inactive hydrogel.

Nanoparticles consisting of metal-organic frameworks (NMOFs) modified with nucleic acid binding strands are synthesized. The NMOFs are loaded with a fluorescent agent or with the anticancer drug doxorubicin, and the loaded NMOFs are capped by hybridization with a complementary nucleic acid that includes the ATP-aptamer or the ATP-AS1411 hybrid aptamer in caged configurations. The NMOFs are unlocked in the presence of ATP via the formation of ATP-aptamer complexes, resulting in the release of the loads. As ATP is overexpressed in cancer cells, and since the AS1411 aptamer recognizes the nucleolin receptor sites on the cancer cell membrane, the doxorubicin-loaded NMOFs provide functional carriers for targeting and treatment of cancer cells. Preliminary cell experiments reveal impressive selective permeation of the NMOFs into MDA-MB-231 breast cancer cells as compared to MCF-10A normal epithelial breast cells. High cytotoxic efficacy and targeted drug release are observed with the ATP-AS1411-functionalized doxorubicin-loaded NMOFs. The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adfm.201702102.conductivity material for fuel cells, [16][17][18] and as a composite material for sensing applications. [4,[19][20][21] Substantial recent efforts are directed toward the development of stimulitriggered reconfigurable nucleic acid structures (DNA switches and DNA machines). [22][23][24][25][26][27] Porous inorganic materials, e.g., SiO 2 nanoparticles, [28] microcapsules, [29] or organic hydrogels, [30][31][32] were loaded with substrates (or drugs) and caged with stimuli-responsive nucleic acid locks. In the presence of appropriate triggers, the stimuli-responsive loaded matrices were unlocked, resulting in the release of the loads. Different stimuli such as pH, [33] light, [34] heat, [35] catalytic nucleic acids, [36] or aptamer-ligand complexes [37] were used to unlock the substrate-loaded materials. Naturally, the capping of the highly porous substrate-loaded MOFs with stimuli-responsive DNAs could yield efficient DNA/ MOFs hybrids as drug delivery systems. Despite the chemical modification of MOFs with stimuli-responsive chemical capping units, [38][39][40][41][42][43] the integration of nucleic acids with MOFs is scarce and involved only the carrying of DNA. [44][45][46][47] Recently, we reported [48] on the successful entrapment of substrates in macrocrystalline MOFs protected by pH-responsive or K + -stabilized G-quadruplex capping units and the triggered unlocking of the MOFs, and the release of loads, by altering the pH, or their treatment with 18-crown-6 ether. While this study demonstrated the successful synthesis of stimuli-responsive DNAgated, substrate-loaded, microcrystalline MOFs, these materials suffer from a basic limitation because they are nonpermeable into cells. That is, their potential application as stimuli-responsive drug carriers is limited. The synthesis of nanometersized MOF particles is well established, [49][50][51][52][53][54] but ...

DNA nanotechnology is a rapidly developing research area in nanoscience. It includes the development of DNA machines, tailoring of DNA nanostructures, application of DNA nanostructures for computing, and more. Different DNA machines were reported in the past and DNA-guided assembly of nanoparticles represents an active research effort in DNA nanotechnology. Several DNA-dictated nanoparticle structures were reported, including a tetrahedron, a triangle or linear nanoengineered nanoparticle structures; however, the programmed, dynamic reversible switching of nanoparticle structures and, particularly, the dictated switchable functions emerging from the nanostructures, are missing elements in DNA nanotechnology. Here we introduce DNA catenane systems (interlocked DNA rings) as molecular DNA machines for the programmed, reversible and switchable arrangement of different-sized gold nanoparticles. We further demonstrate that the machine-powered gold nanoparticle structures reveal unique emerging switchable spectroscopic features, such as plasmonic coupling or surface-enhanced fluorescence.

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