Chad A Mirkin

Northwestern University, Evanston, Illinois, United States

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Publications (700)7095.79 Total impact

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    ABSTRACT: The concept of using cantilever-free scanning probe arrays as structures that can modulate nanoscale ink flow and composition with light is introduced and evaluated. By utilizing polymer pen arrays with an opaque gold layer surrounding the base of the transparent polymer pyramids, we show that inks with photopolymerizable or isomerizable constituents can be used in conjunction with light channelled through the pyramids to control ink viscosity or composition in a dynamic manner. This on-tip photo-modulated molecular printing provides novel chemically and mechanically controlled approaches to regulating ink transport and composition in real time and could be useful not only for rapidly adjusting feature size but also for studying processes including photoreactions and mass transport at the nanoscale, self-assembly, and cell-material interactions.
    Angewandte Chemie International Edition 09/2015; DOI:10.1002/anie.201505150 · 11.26 Impact Factor
  • Chemical Reviews 08/2015; DOI:10.1021/acs.chemrev.5b00321 · 46.57 Impact Factor
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    ABSTRACT: By grafting multiple DNA strands onto one terminus of a polyester chain, a DNA-brush block copolymer that can assemble into micelle structure is constructed. These micelle spherical nucleic acids have a density of nucleic acids that is substantively higher than linear DNA block copolymer structures, which makes them effective cellular transfection and intracellular gene regulation agents. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Small 08/2015; DOI:10.1002/smll.201501573 · 8.37 Impact Factor
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    ABSTRACT: Bottom-up assemblies of plasmonic nanoparticles exhibit unique optical effects such as tunable reflection, optical cavity modes, and tunable photonic resonances. Here, we compare detailed simulations with experiment to explore the effect of structural inhomogeneity on the optical response in DNA-gold nanoparticle superlattices. In particular, we explore the effect of background environment, nanoparticle polydispersity (>10%), and variation in nanoparticle placement (∼5%). At volume fractions less than 20% Au, the optical response is insensitive to particle size, defects, and inhomogeneity in the superlattice. At elevated volume fractions (20% and 25%), structures incorporating different sized nanoparticles (10-, 20-, and 40-nm diameter) each exhibit distinct far-field extinction and near-field properties. These optical properties are most pronounced in lattices with larger particles, which at fixed volume fraction have greater plasmonic coupling than those with smaller particles. Moreover, the incorporation of experimentally informed inhomogeneity leads to variation in far-field extinction and inconsistent electric-field intensities throughout the lattice, demonstrating that volume fraction is not sufficient to describe the optical properties of such structures. These data have important implications for understanding the role of particle and lattice inhomogeneity in determining the properties of plasmonic nanoparticle lattices with deliberately designed optical properties.
    Proceedings of the National Academy of Sciences 08/2015; 112(33):10292-10297. DOI:10.1073/pnas.1513058112 · 9.67 Impact Factor
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    ABSTRACT: Ribozymes are highly structured RNA sequences that can be tailored to recognize and cleave specific stretches of mRNA. Their current therapeutic efficacy remains low due to their large size and structural instability compared to shorter therapeutically relevant RNA such as small interfering RNA (siRNA) and microRNA (miRNA). Herein, a synthetic strategy that makes use of the spherical nucleic acid (SNA) architecture to stabilize ribozymes and transfect them into live cells is reported. The properties of this novel ribozyme-SNA are characterized in the context of the targeted knockdown of O(6)-methylguanine-DNA methyltransferase (MGMT), a DNA repair protein involved in chemotherapeutic resistance of solid tumors, foremost glioblastoma multiforme (GBM). Data showing the direct cleavage of full-length MGMT mRNA, knockdown of MGMT protein, and increased sensitization of GBM cells to therapy-mediated apoptosis, independent of transfection agents, provide compelling evidence for the promising properties of this new chemical architecture.
    Journal of the American Chemical Society 08/2015; DOI:10.1021/jacs.5b07104 · 12.11 Impact Factor
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    ABSTRACT: We report a novel spherical nucleic acid (SNA) gold nanoparticle conjugate, termed the Sticky-flare, which enables facile quantification of RNA expression in live cells and spatiotemporal analysis of RNA transport and localization. The Sticky-flare is capable of entering live cells without the need for transfection agents and recognizing target RNA transcripts in a sequence-specific manner. On recognition, the Sticky-flare transfers a fluorophore-conjugated reporter to the transcript, resulting in a turning on of fluorescence in a quantifiable manner and the fluorescent labeling of targeted transcripts. The latter allows the RNA to be tracked via fluorescence microscopy as it is transported throughout the cell. We use this novel nanoconjugate to analyze the expression level and spatial distribution of β-actin mRNA in HeLa cells and to observe the real-time transport of β-actin mRNA in mouse embryonic fibroblasts. Furthermore, we investigate the application of Sticky-flares for tracking transcripts that undergo more extensive compartmentalization by fluorophore-labeling U1 small nuclear RNA and observing its distribution in the nucleus of live cells.
    Proceedings of the National Academy of Sciences 07/2015; 112(31). DOI:10.1073/pnas.1510581112 · 9.67 Impact Factor
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    ABSTRACT: Understanding the surface structure of metal nanocrystals with specific facet indices is important due to its impact on controlling nanocrystal shape and functionality. However, this is particularly challenging for halide-adsorbed nanocrystals due to the difficulty in analysing interactions between metals and light halides (for example, chloride). Here we uncover the surface structures of chloride-adsorbed, silver-coated gold nanocrystals with {111}, {110}, {310} and {720} indexed facets by X-ray absorption spectroscopy and density functional theory modelling. The silver-chloride, silver-silver and silver-gold bonding structures are markedly different between the nanocrystal surfaces, and are sensitive to their formation mechanism and facet type. A unique approach of combining the density functional theory and experimental/simulated X-ray spectroscopy further verifies the surface structure models and identifies the previously indistinguishable valence state of silver atoms on the nanocrystal surfaces. Overall, this work elucidates the thus-far unknown chloride-metal nanocrystal surface structures and sheds light onto the halide-induced growth mechanism of anisotropic nanocrystals.
    Nature Communications 07/2015; 6:7664. DOI:10.1038/ncomms8664 · 11.47 Impact Factor
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    ABSTRACT: Alloy nanoparticles are important in many fields, including catalysis, plasmonics, and electronics, due to the chemical and physical properties that arise from the interactions between their components. Typically, alloy nanoparticles are made by solution-based synthesis; however, scanning-probe-based methods offer the ability to make and position such structures on surfaces with nanometer-scale resolution. In particular, scanning probe block copolymer lithography (SPBCL), which combines elements of block copolymer lithography with scanning probe techniques, allows one to synthesize nanoparticles with control over particle diameter in the 2−50 nm range. Thus far, single-element structures have been studied in detail, but, in principle, one could make a wide variety of multicomponent systems by controlling the composition of the polymer ink, polymer feature size, and metal precursor concentrations. Indeed, it is possible to use this approach to synthesize alloy nanoparticles comprised of combinations of Au, Ag, Pd, Ni, Co, and Pt. Here, such structures have been made with diameters deliberately tailored in the 10− 20 nm range and characterized by STEM and EDS for structural and elemental composition. The catalytic activity of one class of AuPd alloy nanoparticles made via this method was evaluated with respect to the reduction of 4-nitrophenol with NaBH 4. In addition to being the first catalytic studies of particles made by SPBCL, these proof-of-concept experiments demonstrate the potential for SPBCL as a new method for studying the fundamental science and potential applications of alloy nanoparticles in areas such as heterogeneous catalysis.
    Journal of the American Chemical Society 07/2015; 137(28). DOI:10.1021/jacs.5b05139 · 12.11 Impact Factor
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    ABSTRACT: We report a template-based technique for the preparation of solution-dispersible nanorings composed of Au, Ag, Pt, Ni, and Pd with control over outer diameter (60–400 nm), inner diameter (25–230 nm), and height (40 nm to a few microns). Systematic and independent control of these parameters enables fine-tuning of the three characteristic localized surface plasmon resonance modes of Au nanorings and the resulting solution-based extinction spectra from the visible to the near-infrared. This synthetic approach provides a new pathway for solution-based investigations of surfaces with negative curvature.
    Nano Letters 07/2015; 15(8). DOI:10.1021/acs.nanolett.5b01594 · 13.59 Impact Factor
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    ABSTRACT: Herein, we report an example of entropy-driven crystallization behavior in DNA-nanoparticle superlattice assembly, marking a divergence from the well-established enthalpic driving force of maximizing nearest-neighbor hybridization connections. Such behavior is manifested in the observation of a non-close-packed, body-centered cubic (bcc) superlattice when using a system with self-complementary DNA linkers that would be predicted to form a close-packed, face-centered cubic (fcc) structure based solely on enthalpic considerations and previous design rules for DNA-linked particle assembly. Notably, this unexpected phase behavior is only observed when employing long DNA linkers with unpaired "flexor" bases positioned along the length of the DNA linker that increase the number of microstates available to the DNA ligands. A range of design conditions are tested showing sudden onsets of this behavior, and these experiments are coupled with coarse-grained molecular dynamics simulations to show that this entropy-driven crystallization behavior is due to the accessibility of additional microstates afforded by using long and flexible linkers.
    Nano Letters 06/2015; 15(8). DOI:10.1021/acs.nanolett.5b02129 · 13.59 Impact Factor
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    ABSTRACT: We report the design and synthesis of small molecules that exhibit enhanced luminescence in the presence of duplex rather than single-stranded DNA. The local environment presented by a well-known [Ru(dipyrido[3,2-a:2',3'-c]phenazine)L2 ](2+) -based DNA intercalator was modified by functionalizing the bipyridine ligands with esters and carboxylic acids. By systematically varying the number and charge of the pendant groups, it was determined that decreasing the electrostatic interaction between the intercalator and the anionic DNA backbone reduced single-strand interactions and translated to better duplex specificity. In studying this class of complexes, a single Ru(II) complex emerged that selectively luminesces in the presence of duplex DNA with little to no background from interacting with single-stranded DNA. This complex shows promise as a new dye capable of selectively staining double- versus single-stranded DNA in gel electrophoresis, which cannot be done with conventional SYBR dyes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Chemistry - A European Journal 06/2015; 21(31). DOI:10.1002/chem.201502095 · 5.73 Impact Factor
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    ABSTRACT: Due to their size and tailorable physicochemical properties, nanomaterials are an emerging class of structures utilized in biomedical applications. There are now many prominent examples of nanomaterials being used to improve human health, in areas ranging from imaging and diagnostics to therapeutics and regenerative medicine. An overview of these examples reveals several common areas of synergy and future challenges. This Nano Focus discusses the current status and future potential of promising nanomaterials and their translation from the laboratory to the clinic, by highlighting a handful of successful examples.
    ACS Nano 06/2015; 9(7). DOI:10.1021/acsnano.5b03569 · 12.88 Impact Factor
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    ABSTRACT: The sequence-dependent cellular uptake of spherical nucleic acid nanoparticle conjugates (SNAs) is investigated. This process occurs by interaction with class A scavenger receptors (SR-A) and caveolae-mediated endocytosis. It is known that linear poly(guanine) (poly G) is a natural ligand for SR-A, and it has been proposed that interaction of poly G with SR-A is dependent on the formation of G-quadruplexes. Since G-rich oligonucleotides are known to interact strongly with SR-A, it is hypothesized that SNAs with higher G contents would be able to enter cells in larger amounts than SNAs composed of other nucleotides, and as such, cellular internalization of SNAs is measured as a function of constituent oligonucleotide sequence. Indeed, SNAs with enriched G content show the highest cellular uptake. Using this hypothesis, a small molecule (camptothecin) is chemically conjugated with SNAs to create drug-SNA conjugates and it is observed that poly G SNAs deliver the most camptothecin to cells and have the highest cytotoxicity in cancer cells. Our data elucidate important design considerations for enhancing the intracellular delivery of spherical nucleic acids. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Small 06/2015; 11(33). DOI:10.1002/smll.201500027 · 8.37 Impact Factor
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    ABSTRACT: Control of both photonic and plasmonic coupling in a single optical device represents a challenge due to the distinct length scales that must be manipulated. Here, we show that optical metasurfaces with such control can be constructed using an approach that combines top-down and bottom-up processes, wherein gold nanocubes are assembled into ordered arrays via DNA hybridization events onto a gold film decorated with DNA-binding regions defined using electron beam lithography. This approach enables one to systematically tune three critical architectural parameters: (1) anisotropic metal nanoparticle shape and size, (2) the distance between nanoparticles and a metal surface, and (3) the symmetry and spacing of particles. Importantly, these parameters allow for the independent control of two distinct optical modes, a gap mode between the particle and the surface and a lattice mode that originates from cooperative scattering of many particles in an array. Through reflectivity spectroscopy and finite-difference time-domain simulation, we find that these modes can be brought into resonance and coupled strongly. The high degree of synthetic control enables the systematic study of this coupling with respect to geometry, lattice symmetry, and particle shape, which together serve as a compelling example of how nanoparticle-based optics can be useful to realize advanced nanophotonic structures that hold implications for sensing, quantum plasmonics, and tunable absorbers.
    Nano Letters 06/2015; 15(7). DOI:10.1021/acs.nanolett.5b01548 · 13.59 Impact Factor
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    ABSTRACT: Coordination chemistry is regularly used to generate supramolecular constructs with unique environments around embedded components to affect their intrinsic properties. In certain cases, it can also be used to effect changes in supramolecular structure reminiscent of those that occur within stimuli-responsive biological structures, such as allosteric enzymes. Indeed, among a handful of general strategies for synthesizing such supramolecular systems, the weak-link approach (WLA) uniquely allows one to toggle the frameworks' structural state post-assembly via simple reactions involving hemilabile ligands and transition metal centers. This synthetic strategy, when combined with dynamic ligand sorting processes, represents one of the few sets of general reactions in inorganic chemistry that allow one to synthesize spatially defined, stimuli-responsive, and multi-component frameworks in high to quantitative yields and with remarkable functional group tolerance. The WLA has thus yielded a variety of functional systems that operate similarly to allosteric enzymes, toggling activity via changes in the frameworks' steric confinement or electronic state upon the recognition of small molecule inputs. In this Perspective we present the first full description of the fundamental inorganic reactions that provide the foundation for synthesizing WLA complexes. In addition, we discuss the application of regulatory strategies in biology to the design of allosteric supramolecular constructs for the regulation of various catalytic properties, electron-transfer processes, and molecular receptors, as well as for the development of sensing and signal amplification systems.
    Journal of the American Chemical Society 06/2015; 137(23). DOI:10.1021/jacs.5b01054 · 12.11 Impact Factor
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    ABSTRACT: Whether two species will co-crystallize depends on the chemical, physical and structural complementarity of the interacting components. Here, by using DNA as a surface ligand, we selectively co-crystallize mixtures of two different anisotropic nanoparticles and systematically investigate the effects of nanoparticle size and shape complementarity on the resultant crystal symmetry, microstrain, and effective 'DNA bond' length and strength. We then use these results to understand a more complicated system where both size and shape complementarity change, and where one nanoparticle can participate in multiple types of directional interactions. Our findings offer improved control of non-spherical nanoparticles as building blocks for the assembly of sophisticated macroscopic materials, and provide a framework to understand complementarity and directional interactions in DNA-mediated nanoparticle crystallization.
    Nature Material 05/2015; 14(8). DOI:10.1038/nmat4293 · 36.50 Impact Factor
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    ABSTRACT: Complementary tetrahedral small molecule-DNA hybrid (SMDH) building blocks have been combined to form nucleic acid-based polymeric nanoparticles without the need for an underlying template or scaffold. The sizes of these particles can be tailored in a facile fashion by adjusting assembly conditions such as SMDH concentration, assembly time, and NaCl concentration. Notably, these novel particles can be stabilized and transformed into functionalized spherical nucleic acid (SNA) structures by the incorporation of capping DNA strands conjugated with functional groups. These results demonstrate a systematic, efficient strategy for the construction and surface functionalization of well-defined, size-tunable nucleic acid particles from readily accessible molecular building blocks. Furthermore, because these nucleic acid-based polymeric nanoparticles exhibited enhanced cellular internalization and resistance against DNase I compared to free synthetic nucleic acids, they should have a plethora of applications in diagnostics and therapeutics.
    Journal of the American Chemical Society 05/2015; 137(25). DOI:10.1021/jacs.5b03485 · 12.11 Impact Factor
  • SIAM Journal on Scientific Computing 05/2015; 37(3):B361-B381. DOI:10.1137/140971117 · 1.85 Impact Factor
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    ABSTRACT: Spherical or nucleic acid (SNA) gold nanoparticle conjugates (13-nm-diameter gold cores functionalized with densely packed and highly oriented nucleic acids) dispersed in Aquaphor have been shown to penetrate the epidermal barrier of both intact mouse and human skin, enter keratinocytes, and efficiently down-regulate gene targets. ganglioside-monosialic acid 3 synthase (GM3S) is a known target that is overexpressed in diabetic mice and responsible for causing insulin resistance and impeding wound healing. GM3S SNAs increase keratinocyte migration and proliferation as well as insulin and insulin-like growth factor-1 (IGF1) receptor activation under both normo- and hyperglycemic conditions. The topical application of GM3S SNAs (50 nM) to splinted 6-mm-diameter full-thickness wounds in diet-induced obese diabetic mice decreases local GM3S expression by >80% at the wound edge through an siRNA pathway and fully heals wounds clinically and histologically within 12 d, whereas control-treated wounds are only 50% closed. Granulation tissue area, vascularity, and IGF1 and EGF receptor phosphorylation are increased in GM3S SNA-treated wounds. These data capitalize on the unique ability of SNAs to naturally penetrate the skin and enter keratinocytes without the need for transfection agents. Moreover, the data further validate GM3 as a mediator of the delayed wound healing in type 2 diabetes and support regional GM3 depletion as a promising therapeutic direction.
    Proceedings of the National Academy of Sciences 05/2015; 112(18):201505951. DOI:10.1073/pnas.1505951112 · 9.67 Impact Factor

Publication Stats

62k Citations
7,095.79 Total Impact Points


  • 1992–2015
    • Northwestern University
      • Department of Chemistry
      Evanston, Illinois, United States
  • 2004–2014
    • Northwest University
      Evanston, Illinois, United States
  • 2006–2013
    • International Council on Nanotechnology
      INL, Minnesota, United States
    • Texas A&M University
      College Station, Texas, United States
    • Rushford Institute for NanoTechnology (RINTek)
      Rushford, Minnesota, United States
  • 2011
    • University of Virginia
      Charlottesville, Virginia, United States
    • University of New Mexico
      • Department of Chemical and Nuclear Engineering
      Albuquerque, NM, United States
    • University of Washington Seattle
      • Department of Chemistry
      Seattle, WA, United States
  • 2010
    • University of Münster
      • Institute of Geophysics
      Muenster, North Rhine-Westphalia, Germany
  • 2007
    • Johns Hopkins University
      • Department of Chemistry
      Baltimore, Maryland, United States
  • 2005
    • University of Illinois, Urbana-Champaign
      • Department of Electrical and Computer Engineering
      Urbana, IL, United States
    • City Colleges of Chicago Harold Washington College
      Chicago, Illinois, United States
  • 1986–2003
    • University of Delaware
      • Department of Chemistry and Biochemistry
      Ньюарк, Delaware, United States
  • 1996
    • University of Texas at Austin
      • Department of Chemistry and Biochemistry
      Austin, Texas, United States
  • 1994
    • Western Illinois University
      • Department of Chemistry
      MQB, Illinois, United States
  • 1990–1992
    • Massachusetts Institute of Technology
      • Department of Chemistry
      Cambridge, Massachusetts, United States