DNA nanotechnology: from sensing and DNA machines to drug-delivery systems.

DNA/nanoparticle hybrid systems combine the unique electronic and optical properties of nanomaterials with the recognition and catalytic properties of nucleic acids. These materials hold great promise for the development of new sensing platforms, the programmed organization of nanoparticles, the switchable control of plasmonic phenomena in the nanostructures, and the controlled delivery of drugs. In this Perspective, we summarize recent advances in the application of DNA/nanoparticle (NP) hybrids in these different disciplines. Nucleic acid-semiconductor quantum dot hybrids are implemented to develop multiplexed sensing platforms for targeted DNA. The chemiluminescence resonance energy transfer mechanism is introduced as a new transduction signal, and the amplified detection of DNA targets through the biocatalytic regeneration of analytes is demonstrated. DNA machines consisting of catenanes or tweezers, and modified with fluorophore/Au NP pairs are used as functional devices for the switchable "mechanical" control of the fluorescence properties of the fluorophore. Also, nucleic acid nanostructures act as stimuli-responsive caps for trapping drugs in the pores of mesoporous SiO2 nanoparticles. In the presence of appropriate biomarker triggers, the pores are unlocked, leading to the controlled release of anticancer drugs. Selective cancer-cell death is demonstrated with the stimuli-responsive SiO2 nanoparticles.

[1]  A. Turberfield,et al.  A DNA-fuelled molecular machine made of DNA , 2022 .

[2]  Michael Krueger,et al.  Sequence-Specific Molecular Lithography on Single DNA Molecules , 2002, Science.

[3]  Itamar Willner,et al.  All-DNA finite-state automata with finite memory , 2010, Proceedings of the National Academy of Sciences.

[4]  Takashi Fujimoto,et al.  MercuryII-mediated formation of thymine-HgII-thymine base pairs in DNA duplexes. , 2006, Journal of the American Chemical Society.

[5]  J. Szostak,et al.  In vitro selection of RNA molecules that bind specific ligands , 1990, Nature.

[6]  A. Polman,et al.  Plasmon-enhanced luminescence near noble-metal nanospheres: Comparison of exact theory and an improved Gersten and Nitzan model , 2007 .

[7]  Itamar Willner,et al.  Amplified surface plasmon resonance and electrochemical detection of Pb2+ ions using the Pb2+-dependent DNAzyme and hemin/G-quadruplex as a label. , 2012, Analytical chemistry.

[8]  I. Willner,et al.  DNA nanotechnology with one-dimensional self-assembled nanostructures. , 2013, Current opinion in biotechnology.

[9]  A. Ono,et al.  Specific interactions between silver(I) ions and cytosine-cytosine pairs in DNA duplexes. , 2008, Chemical communications.

[10]  F. Xiao,et al.  pH-responsive carrier system based on carboxylic acid modified mesoporous silica and polyelectrolyte for drug delivery , 2005 .

[11]  Juewen Liu,et al.  Functional nucleic acid sensors. , 2009, Chemical reviews.

[12]  Dmitry M. Kolpashchikov,et al.  Binary probes for nucleic acid analysis. , 2010, Chemical reviews.

[13]  Itamar Willner,et al.  Catalytic beacons for the detection of DNA and telomerase activity. , 2004, Journal of the American Chemical Society.

[14]  Xingguo Liang,et al.  A DNA Nanomachine Powered by Light Irradiation , 2008, Chembiochem : a European journal of chemical biology.

[15]  P. Alivisatos.  The use of nanocrystals in biological detection , 2004, Nature Biotechnology.

[16]  Shawn M. Douglas,et al.  A Logic-Gated Nanorobot for Targeted Transport of Molecular Payloads , 2012, Science.

[17]  Itamar Willner,et al.  Organizing protein-DNA hybrids as nanostructures with programmed functionalities. , 2010, Trends in biotechnology.

[18]  Yi Xiao,et al.  Amplified chemiluminescence surface detection of DNA and telomerase activity using catalytic nucleic acid labels. , 2004, Analytical chemistry.

[19]  Friedrich C Simmel,et al.  A DNA-based machine that can cyclically bind and release thrombin. , 2004, Angewandte Chemie.

[20]  M. Guéron,et al.  A tetrameric DNA structure with protonated cytosine-cytosine base pairs , 1993, Nature.

[21]  F. Caruso,et al.  Mesoporous Silica Particles as Templates for Preparing Enzyme‐Loaded Biocompatible Microcapsules , 2005 .

[22]  N. Seeman,et al.  Design and self-assembly of two-dimensional DNA crystals , 1998, Nature.

[23]  María Vallet-Regí,et al.  Mesoporous Materials for Drug Delivery , 2008 .

[24]  Jeffrey I. Zink,et al.  Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery , 2010, BiOS.

[25]  Plamen Atanassov,et al.  Photoregulation of Mass Transport through a Photoresponsive Azobenzene-Modified Nanoporous Membrane , 2004 .

[26]  Faisal A. Aldaye,et al.  Assembling Materials with DNA as the Guide , 2008, Science.

[27]  I. Willner,et al.  Light-induced and redox-triggered uptake and release of substrates to and from mesoporous SiO2 nanoparticles. , 2013, Journal of materials chemistry. B.

[28]  I. Willner,et al.  Metal nanoparticle-functionalized DNA tweezers: from mechanically programmed nanostructures to switchable fluorescence properties. , 2013, Nano letters.

[29]  Yamuna Krishnan,et al.  A DNA nanomachine that maps spatial and temporal pH changes inside living cells. , 2009, Nature nanotechnology.

[30]  Itamar Willner,et al.  Powering the programmed nanostructure and function of gold nanoparticles with catenated DNA machines , 2013, Nature Communications.

[31]  Robert M. Dickson,et al.  Developing luminescent silver nanodots for biological applications. , 2012, Chemical Society reviews.

[32]  Cuichen Wu,et al.  Responsive DNA-based hydrogels and their applications. , 2013, Macromolecular rapid communications.

[33]  V. S. Lin,et al.  Mesoporous silica nanoparticle-based double drug delivery system for glucose-responsive controlled release of insulin and cyclic AMP. , 2009, Journal of the American Chemical Society.

[34]  Yamuna Krishnan,et al.  Two DNA nanomachines map pH changes along intersecting endocytic pathways inside the same cell. , 2013, Nature nanotechnology.

[35]  Paul Mulvaney,et al.  Synthesis and electronic properties of semiconductor nanoparticles/quantum dots , 2000 .

[36]  Qiuping Guo,et al.  A new class of homogeneous nucleic acid probes based on specific displacement hybridization. , 2002, Nucleic acids research.

[37]  G. Seelig,et al.  Dynamic DNA nanotechnology using strand-displacement reactions. , 2011, Nature chemistry.

[38]  Itamar Willner,et al.  pH-programmable DNA logic arrays powered by modular DNAzyme libraries. , 2012, Nano letters.

[39]  I. Willner,et al.  pH-stimulated concurrent mechanical activation of two DNA "tweezers". A "SET-RESET" logic gate system. , 2009, Nano letters.

[40]  Itamar Willner,et al.  DNAzymes for sensing, nanobiotechnology and logic gate applications. , 2008, Chemical Society reviews.

[41]  R R Breaker,et al.  A DNA enzyme that cleaves RNA. , 1994, Chemistry & biology.

[42]  I. Willner,et al.  Nucleic acid/quantum dots (QDs) hybrid systems for optical and photoelectrochemical sensing. , 2013, ACS applied materials & interfaces.

[43]  Jehoshua Bruck,et al.  Neural network computation with DNA strand displacement cascades , 2011, Nature.

[44]  Itamar Willner,et al.  Optical aptasensors for the analysis of the vascular endothelial growth factor (VEGF). , 2012, Analytical chemistry.

[45]  L. Gold,et al.  Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. , 1990, Science.

[46]  I. Willner,et al.  Amplified multiplexed analysis of DNA by the exonuclease III-catalyzed regeneration of the target DNA in the presence of functionalized semiconductor quantum dots. , 2011, Nano letters.

[47]  Itamar Willner,et al.  Smart mesoporous SiO2 nanoparticles for the DNAzyme-induced multiplexed release of substrates. , 2013, Journal of the American Chemical Society.

[48]  Itamar Willner,et al.  Chemiluminescent and chemiluminescence resonance energy transfer (CRET) detection of DNA, metal ions, and aptamer-substrate complexes using hemin/G-quadruplexes and CdSe/ZnS quantum dots. , 2011, Journal of the American Chemical Society.

[49]  Erik Winfree,et al.  Molecular robots guided by prescriptive landscapes , 2010, Nature.

[50]  I. Willner,et al.  Biocatalytic release of an anticancer drug from nucleic-acids-capped mesoporous SiO2 Using DNA or molecular biomarkers as triggering stimuli. , 2013, ACS nano.

[51]  Itamar Willner,et al.  Graphene oxide/nucleic-acid-stabilized silver nanoclusters: functional hybrid materials for optical aptamer sensing and multiplexed analysis of pathogenic DNAs. , 2013, Journal of the American Chemical Society.

[52]  I. Willner,et al.  Chemiluminescence and chemiluminescence resonance energy transfer (CRET) aptamer sensors using catalytic hemin/G-quadruplexes. , 2011, ACS nano.

[53]  I. Willner,et al.  Functionalized DNA nanostructures. , 2012, Chemical reviews.

[54]  Itamar Willner,et al.  Semiconductor Quantum Dots for Bioanalysis , 2008 .

[55]  Chunhai Fan,et al.  Target-responsive structural switching for nucleic acid-based sensors. , 2010, Accounts of chemical research.

[56]  Jeffery T. Davis,et al.  Supramolecular Architectures Generated by Self-Assembly of Guanosine Derivatives , 2007 .

[57]  Gavin W. Collie,et al.  The Application of DNA and RNA G‐Quadruplexes to Therapeutic Medicines , 2012 .