Chad A Mirkin

Northwestern University, Evanston, Illinois, United States

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Publications (667)6451 Total impact

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    ABSTRACT: Carboranethiol molecules self-assemble into upright molecular monolayers on Au{111} with aligned dipoles in two dimensions. The positions and offsets of each molecule’s geometric apex and local dipole moment are measured and correlated with sub-Ångström precision. Juxtaposing simultaneously acquired images, we observe monodirectional offsets between the molecular apexes and dipole maxima. We determine dipole orientations using efficient new image analysis techniques and find aligned dipoles to be highly defect tolerant, crossing molecular domain boundaries and substrate step edges. The alignment observed, consistent with Monte Carlo simulations, forms through favorable intermolecular dipole-dipole interactions.
    ACS Nano 04/2015; 9. DOI:10.1021/acsnano.5b01329 · 12.03 Impact Factor
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    ABSTRACT: The nanoscale manipulation of matter allows properties to be created in a material that would be difficult or even impossible to achieve in the bulk state. Progress towards such functional nanoscale architectures requires the development of methods to precisely locate nanoscale objects in three dimensions and for the formation of rigorous structure-function relationships across multiple size regimes (beginning from the nanoscale). Here, we use DNA as a programmable ligand to show that two- and three-dimensional mesoscale superlattice crystals with precisely engineered optical properties can be assembled from the bottom up. The superlattices can transition from exhibiting the properties of the constituent plasmonic nanoparticles to adopting the photonic properties defined by the mesoscale crystal (here a rhombic dodecahedron) by controlling the spacing between the gold nanoparticle building blocks. Furthermore, we develop a generally applicable theoretical framework that illustrates how crystal habit can be a design consideration for controlling far-field extinction and light confinement in plasmonic metamaterial superlattices.
    Nature Nanotechnology 04/2015; DOI:10.1038/nnano.2015.68 · 33.27 Impact Factor
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    ABSTRACT: A novel method for preparing conformal silica-embedded crystalline nanoparticle sheets via DNA programmable assembly provides independent control over nanoparticle size, nanoparticle spacing, and film thickness. The conformal materials retain the nanoparticle crystallinity and spacing after being transferred to flat or highly curved substrates even after being subjected to various mechanical, physical, and chemical stimuli. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Advanced Materials 04/2015; DOI:10.1002/adma.201500858 · 15.41 Impact Factor
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    Journal of Magnetism and Magnetic Materials 04/2015; 379:239-243. DOI:10.1016/j.jmmm.2014.12.049 · 2.00 Impact Factor
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    ABSTRACT: Glioblastoma multiforme (GBM) is a lethal, therapy-resistant brain cancer consisting of numerous tumor cell subpopulations, including stem-like glioma-initiating cells (GICs), which contribute to tumor recurrence following initial response to therapy. Here, we identified miR-182 as a regulator of apoptosis, growth, and differentiation programs whose expression level is correlated with GBM patient survival. Repression of Bcl2-like12 (Bcl2L12), c-Met, and hypoxia-inducible factor 2α (HIF2A) is of central importance to miR-182 anti-tumor activity, as it results in enhanced therapy susceptibility, decreased GIC sphere size, expansion, and stemness in vitro. To evaluate the tumor-suppressive function of miR-182 in vivo, we synthesized miR-182-based spherical nucleic acids (182-SNAs); i.e., gold nanoparticles covalently functionalized with mature miR-182 duplexes. Intravenously administered 182-SNAs penetrated the blood-brain/blood-tumor barriers (BBB/BTB) in orthotopic GBM xenografts and selectively disseminated throughout extravascular glioma parenchyma, causing reduced tumor burden and increased animal survival. Our results indicate that harnessing the anti-tumor activities of miR-182 via safe and robust delivery of 182-SNAs represents a novel strategy for therapeutic intervention in GBM. © 2015 Kouri et al.; Published by Cold Spring Harbor Laboratory Press.
    Genes & development 04/2015; 29(7):732-45. DOI:10.1101/gad.257394.114 · 12.64 Impact Factor
  • SPIENewsroom 04/2015; DOI:10.1117/2.1201503.005823
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    ABSTRACT: Biological photosynthetic machinery allosterically regulate light harvesting via conformational and electronic changes at the antenna protein complexes as a response to specific chemical inputs. Fundamental limitations in current approaches to regulating inorganic light-harvesting mimics prevent their use in catalysis. Here we show that a light-harvesting antenna/reaction centre mimic can be regulated by utilizing a coordination framework incorporating antenna hemilabile ligands and assembled via a high-yielding, modular approach. As in nature, allosteric regulation is afforded by coupling the conformational changes to the disruptions in the electrochemical landscape of the framework upon recognition of specific coordinating analytes. The hemilabile ligands enable switching using remarkably mild and redox-inactive inputs, allowing one to regulate the photoredox catalytic activity of the photosynthetic mimic reversibly and in situ. Thus, we demonstrate that bioinspired regulatory mechanisms can be applied to inorganic light-harvesting arrays displaying switchable catalytic properties and with potential uses in solar energy conversion and photonic devices.
    Nature Communications 03/2015; 6:6541. DOI:10.1038/ncomms7541 · 10.74 Impact Factor
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    ABSTRACT: The ability to predictably control the coassembly of multiple nanoscale building blocks, especially those with disparate chemical and physical properties such as biomolecules and inorganic nanoparticles, has far-reaching implications in catalysis, sensing, and photonics, but a generalizable strategy for engineering specific contacts between these particles is an outstanding challenge. This is especially true in the case of proteins, where the types of possible interparticle interactions are numerous, diverse, and complex. Herein, we explore the concept of trading protein-protein interactions for DNA-DNA interactions to direct the assembly of two nucleic-acid-functionalized proteins with distinct surface chemistries into six unique lattices composed of catalytically active proteins, or of a combination of proteins and DNA-modified gold nanoparticles. The programmable nature of DNA-DNA interactions used in this strategy allows us to control the lattice symmetries and unit cell constants, as well as the compositions and habit, of the resulting crystals. This study provides a potentially generalizable strategy for constructing a unique class of materials that take advantage of the diverse morphologies, surface chemistries, and functionalities of proteins for assembling functional crystalline materials.
    Proceedings of the National Academy of Sciences 03/2015; 112(15). DOI:10.1073/pnas.1503533112 · 9.81 Impact Factor
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    ABSTRACT: We show that by organizing immunomodulatory nucleic acids into spherical nucleic acid (SNA) form, significant increases in activity are observed. Treatment of mice with cancer using immunostimulatory SNAs and nonalcoholic steatohepatitis (NASH) using immunoregulatory SNAs leads to improved disease outcomes vs. their unstructured counterparts. These improvements derive from several key SNA properties, including rapid cellular uptake, endosomal delivery, and multivalent binding. Overall, this work underscores the importance of the spatial orientation and presentation of oligonucleotides in the design of novel immunomodulators. Immunomodulatory nucleic acids have extraordinary promise for treating disease, yet clinical progress has been limited by a lack of tools to safely increase activity in patients. Immunomodulatory nucleic acids act by agonizing or antagonizing endosomal toll-like receptors (TLR3, TLR7/8, and TLR9), proteins involved in innate immune signaling. Immunomodulatory spherical nucleic acids (SNAs) that stimulate (immunostimulatory, IS-SNA) or regulate (immunoregulatory, IR-SNA) immunity by engaging TLRs have been designed, synthesized, and characterized. Compared with free oligonucleotides, IS-SNAs exhibit up to 80-fold increases in potency, 700-fold higher antibody titers, 400-fold higher cellular responses to a model antigen, and improved treatment of mice with lymphomas. IR-SNAs exhibit up to eightfold increases in potency and 30% greater reduction in fibrosis score in mice with nonalcoholic steatohepatitis (NASH). Given the clinical potential of SNAs due to their potency, defined chemical nature, and good tolerability, SNAs are attractive new modalities for developing immunotherapies.
    Proceedings of the National Academy of Sciences 03/2015; Early Edition(13). DOI:10.1073/pnas.1502850112 · 9.81 Impact Factor
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    ABSTRACT: The first tritopic carborane-based linker, H3BCA (C15B24O6H30), based on closo-1,10-C2B8H10, has been synthesized and incorporated into a metal-organic framework (MOF), (Cu3(BCA)2). In contrast to the analogous MOF-143, can be activated with retention of porosity, yielding a BET surface area of 1870 m(2) g(-1).
    Chemical Communications 03/2015; DOI:10.1039/c4cc09212k · 6.72 Impact Factor
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    ABSTRACT: The hybridization of free oligonucleotides to densely packed, oriented arrays of DNA modifying the surfaces of spherical nucleic acid (SNA)-gold nanoparticle conjugates occurs with negative cooperativity; i.e., each binding event destabilizes subsequent binding events. DNA hybridization is thus an ever-changing function of the number of strands already hybridized to the particle. Thermodynamic quantification of this behavior reveals a 3 orders of magnitude decrease in the binding constant for the capture of a free oligonucleotide by an SNA conjugate as the fraction of pre-hybridized strands increases from 0 to ∼30%. Increasing the number of pre-hybridized strands imparts an increasing enthalpic penalty to hybridization that makes binding more difficult, while simultaneously decreasing the entropic penalty to hybridization, which makes binding more favorable. Hybridization of free DNA to an SNA is thus governed by both an electrostatic barrier as the SNA accumulates charge with additional binding events and an effect consistent with allostery, where hybridization at certain sites on an SNA modify the binding affinity at a distal site through conformational changes to the remaining single strands. Leveraging these insights allows for the design of conjugates that hybridize free strands with significantly higher efficiencies, some of which approach 100%.
    Journal of the American Chemical Society 03/2015; DOI:10.1021/jacs.5b00670 · 11.44 Impact Factor
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    ABSTRACT: For over half a century, the biological roles of nucleic acids as catalytic enzymes, intracellular regulatory molecules, and the carriers of genetic information have been studied extensively. More recently, the sequence-specific binding properties of DNA have been exploited to direct the assembly of materials at the nanoscale. Integral to any methodology focused on assembling matter from smaller pieces is the idea that final structures have well-defined spacings, orientations, and stereo-relationships. This requirement can be met by using DNA-based constructs that present oriented nanoscale bonding elements from rigid core units. Here, we draw analogy between such building blocks and the familiar chemical concepts of "bonds" and "valency" and review two distinct but related strategies that have used this design principle in constructing new configurations of matter. Copyright © 2015, American Association for the Advancement of Science.
  • Tuncay Ozel, Gilles R. Bourret, Chad A. Mirkin
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    ABSTRACT: The optical and electrical properties of heterogeneous nanowires are profoundly related to their composition and nanoscale architecture1, 2, 3, 4, 5, 6, 7. However, the intrinsic constraints of conventional synthetic and lithographic techniques have limited the types of multi-compositional nanowire that can be created and studied in the laboratory. Here, we report a high-throughput technique that can be used to prepare coaxial nanowires with sub-10 nm control over the architectural parameters in both axial and radial dimensions. The method, termed coaxial lithography (COAL), relies on templated electrochemical synthesis and can create coaxial nanowires composed of combinations of metals, metal oxides, metal chalcogenides and conjugated polymers. To illustrate the possibilities of the technique, a core/shell semiconductor nanowire with an embedded plasmonic nanoring was synthesized—a structure that cannot be prepared by any previously known method—and its plasmon-excitation-dependent optoelectronic properties were characterized. http://www.nature.com/nnano/journal/vaop/ncurrent/full/nnano.2015.33.html
    Nature Nanotechnology 02/2015; DOI:10.1038/nnano.2015.33 · 33.27 Impact Factor
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    ABSTRACT: The ability of high-density lipoprotein (HDL) to support macrophage cholesterol efflux is an integral part of its atheroprotective action. Augmenting this ability, especially when HDL cholesterol efflux capacity from macrophages is poor, represents a promising therapeutic strategy. One approach to enhancing macrophage cholesterol efflux is infusing blood with HDL mimics. Previously, we reported the synthesis of a functional mimic of HDL (fmHDL) that consists of a gold nanoparticle template, a phospholipid bilayer and apolipoprotein A-I. In this work we characterize the ability of fmHDL to support the well-established pathways of cellular cholesterol efflux from model cell lines and primary macrophages. fmHDL received cell cholesterol by unmediated (aqueous) and ATP-binding cassette transporter G1 (ABCG1)- and scavenger receptor class B type I (SR-BI)-mediated diffusion. Furthermore, the fmHDL holoparticle accepted cholesterol and phospholipid by the ATP-binding cassette transporter A1 (ABCA1) pathway. These results demonstrate that fmHDL supports all the cholesterol efflux pathways available to native HDL and thus, represents a promising infusible therapeutic for enhancing macrophage cholesterol efflux. Conclusion: fmHDL accepts cholesterol from cells by all known pathways of cholesterol efflux: unmediated, ABCG1- and SR-BI-mediated diffusion and through ABCA1. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    The Journal of Lipid Research 02/2015; DOI:10.1194/jlr.M054635 · 4.73 Impact Factor
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    ABSTRACT: Herein, we describe a strategy for converting catalytically inactive, highly crystalline nanoparticle superlattices embedded in silica into catalytically active, porous structures through superlattice assembly and calcination. First, a body-centered cubic (bcc) superlattice is synthesized through the assembly of two sets of 5 nm gold nanoparticles chemically modified with DNA bearing complementary sticky end sequences. These superlattices are embedded in silica and calcined at 350 °C to provide access to the catalytic nanoparticle surface sites. The calcined superlattice maintains its bcc ordering and has a surface area of 210 m(2)/g. The loading of catalytically active nanoparticles within the superlattice was determined by inductively coupled plasma mass spectrometry, which revealed that the calcined superlattice contained approximately 10% Au by weight. We subsequently investigate the ability of supported Au nanoparticle superlattices to catalyze alcohol oxidation. In addition to demonstrating that calcined superlattices are effective catalysts for alcohol oxidation, electron microscopy reveals preservation of the crystalline structure of the bcc superlattice following calcination and catalysis. Unlike many bulk nanoparticle catalysts, which are difficult to characterize and susceptible to aggregation, nanoparticle superlattices synthesized using DNA interactions offer an attractive bottom-up route to structurally defined heterogeneous catalysts, where one has the potential to independently control nanoparticle size, nanoparticle compositions, and interparticle spacings.
    Journal of the American Chemical Society 01/2015; 137(4). DOI:10.1021/ja512116p · 11.44 Impact Factor
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    ABSTRACT: Herein, we demonstrate that the incorporation of an acidic hydrogen-bond-donating squaramide moiety into a porous UiO-67 metal-organic framework (MOF) derivative leads to dramatic acceleration of the biorelevant Friedel-Crafts reaction between indole and β-nitrostyrene. In comparison, it is shown that free squaramide derivatives, not incorporated into MOF architectures, have no catalytic activity. Additionally, using the UiO-67 template, we were able to perform a direct comparison of catalytic activity with that of the less acidic urea-based analogue. This is the first demonstration of the functionalization of a heterogeneous framework with an acidic squaramide derivative.
    Journal of the American Chemical Society 01/2015; DOI:10.1021/ja511403t · 11.44 Impact Factor
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    ABSTRACT: To understand the effect of three-dimensional oligonucleotide structure on protein corona formation, we studied the identity and quantity of human serum proteins that bind to spherical nucleic acid (SNA) nanoparticle conjugates. SNAs exhibit cellular uptake properties that are remarkably different from those of linear nucleic acids, which have been related to their interaction with certain classes of proteins. Through a proteomic analysis, this work shows that the protein binding properties of SNAs are sequence-specific and supports the conclusion that the oligonucleotide tertiary structure can significantly alter the chemical composition of the SNA protein corona. This knowledge will impact our understanding of how nucleic acid-based nanostructures, and SNAs in particular, function in complex biological milieu.
    Angewandte Chemie 01/2015; 127(2). DOI:10.1002/ange.201409211
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    ABSTRACT: Herein, we report the synthesis of structurally uniform gold circular disks as two-dimensional plasmonic nanostructures that complement the well-established one-dimensional rod and three-dimensional shell structures. We show that a Au conproportionation reaction can be used to etch a collection of nonuniform triangular prisms into a uniform circular disk product with thickness and diameter varying <10%. These new particles have broadly tunable plasmon resonances (650-1000 nm) with narrow bandwidths (0.23-0.28 eV) and can be described as "effectively two-dimensional" plasmonic structures, as they do not support a significant transverse mode.
    Nano Letters 01/2015; 15(2). DOI:10.1021/nl5038566 · 12.94 Impact Factor
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    ABSTRACT: Patients whose cancer is detected early are much more likely to have a positive prognosis and outcome. Nanoflares hold promise as a practical diagnostic platform for the early detection of cancer markers in living cells. These probes are based on spherical nucleic acid (SNAs) and are typically composed of gold nanoparticle cores and densely packed and highly oriented oligonucleotide shells; these sequences are complementary to specific mRNA targets and are hybridized to fluorophore-labeled reporter strands. Nanoflares take advantage of the highly efficient fluorescence quenching properties of gold, the rapid cellular uptake of SNAs that occurs without the use of transfection agents, and the enzymatic stability of such constructs to report a highly sensitive and specific signal in the presence of intracellular target mRNA. In this chapter, we will focus on the synthesis, characterization, and diagnostic applications of nanoflares as they relate to cancer markers.
    Cancer treatment and research 01/2015; 166:1-22. DOI:10.1007/978-3-319-16555-4_1

Publication Stats

54k Citations
6,451.00 Total Impact Points

Institutions

  • 1995–2015
    • 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
    • City Colleges of Chicago Harold Washington College
      Chicago, Illinois, United States
  • 2004–2005
    • University of Illinois, Urbana-Champaign
      • Department of Electrical and Computer Engineering
      Urbana, IL, United States
  • 1986–2003
    • University of Delaware
      • Department of Chemistry and Biochemistry
      Ньюарк, Delaware, United States
  • 2002
    • Western Illinois University
      • Department of Chemistry
      MQB, Illinois, United States
    • Massachusetts Institute of Technology
      • Department of Chemistry
      Cambridge, Massachusetts, United States
  • 1996
    • University of Texas at Austin
      • Department of Chemistry and Biochemistry
      Austin, Texas, United States
  • 1970
    • Rice University
      • Department of Civil and Environmental Engineering
      Houston, TX, United States
    • University of California, Los Angeles
      • California NanoSystems Institute
      Los Angeles, CA, United States
    • Arizona State University
      • College of Liberal Arts and Sciences
      Tempe, AZ, United States