Chad A Mirkin

Northwestern University, Evanston, Illinois, United States

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Publications (642)6193.27 Total impact

  • Source
    Journal of Magnetism and Magnetic Materials 04/2015; 379:239-243. · 2.00 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; · 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; · 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; · 11.44 Impact Factor
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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;
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    ABSTRACT: Three-dimensional dielectric photonic crystals have well-established enhanced light–matter interactions via high Q factors. Their plasmonic counterparts based on arrays of nanoparticles, however, have not been experimentally well explored owing to a lack of available synthetic routes for preparing them. However, such structures should facilitate these interactions based on the small mode volumes associated with plasmonic polarization. Herein we report strong light-plasmon interactions within 3D plasmonic photonic crystals that have lattice constants and nanoparticle diameters that can be independently controlled in the deep subwavelength size regime by using a DNA-programmable assembly technique. The strong coupling within such crystals is probed with backscattering spectra, and the mode splitting (0.10 and 0.24 eV) is defined based on dispersion diagrams. Numerical simulations predict that the crystal photonic modes (Fabry–Perot modes) can be enhanced by coating the crystals with a silver layer, achi
    Proceedings of the National Academy of Sciences. 01/2015; 112(4):977-981.
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    ABSTRACT: Using on-wire lithography to synthesize well-defined nanorod dimers and trimers, we report a systematic study of the plasmon coupling properties of such materials. By comparing the dimer/trimer structures to discrete nanorods of the same overall length, we demonstrate many similarities between antibonding coupled modes in the dimers/trimers and higher-order resonances in the discrete nanorods. These conclusions are validated with a combination of discrete dipole approximation and finite-difference time-domain calculations and lead to the observation of antibonding modes in symmetric structures by measuring their solution-dispersed extinction spectra. Finally, we probe the effects of asymmetry and gap size on the occurrence of these modes and demonstrate that the delocalized nature of the antibonding modes lead to longer-range coupling compared to the stronger bonding modes.
    Nano Letters 11/2014; · 12.94 Impact Factor
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    ABSTRACT: Metastasis portends a poor prognosis for cancer patients. Primary tumor cells disseminate through the bloodstream before the appearance of detectable metastatic lesions. The analysis of cancer cells in blood-so-called circulating tumor cells (CTCs)-may provide unprecedented opportunities for metastatic risk assessment and investigation. NanoFlares are nanoconstructs that enable live-cell detection of intracellular mRNA. NanoFlares, when coupled with flow cytometry, can be used to fluorescently detect genetic markers of CTCs in the context of whole blood. They allow one to detect as few as 100 live cancer cells per mL of blood and subsequently culture those cells. This technique can also be used to detect CTCs in a murine model of metastatic breast cancer. As such, NanoFlares provide, to our knowledge, the first genetic-based approach for detecting, isolating, and characterizing live cancer cells from blood and may provide new opportunities for cancer diagnosis, prognosis, and personalized therapy.
    Proceedings of the National Academy of Sciences 11/2014; 111(48). · 9.81 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 International Edition in English 11/2014; · 13.45 Impact Factor
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    ABSTRACT: Herein, we report the synthesis of DNA-functionalized infinite-coordination-polymer (ICP) nanoparticles as biocompatible gene-regulation agents. ICP nanoparticles were synthesized from ferric nitrate and a ditopic 3-hydroxy-4-pyridinone (HOPO) ligand bearing a pendant azide. Addition of Fe(III) to a solution of the ligand produced nanoparticles, which were colloidally unstable in the presence of salts. Conjugation of DNA to the Fe(III) -HOPO ICP particles by copper-free click chemistry afforded colloidally stable nucleic-acid nanoconstructs. The DNA-ICP particles, when cross-linked through sequence-specific hybridization, exhibited narrow, highly cooperative melting transitions consistent with dense DNA surface loading. The ability of the DNA-ICP particles to enter cells and alter protein expression was also evaluated. Our results indicate that these novel particles carry nucleic acids into mammalian cells without the need for transfection agents and are capable of efficient gene knockdown.
    Angewandte Chemie International Edition in English 11/2014; · 13.45 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 11/2014;
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    ABSTRACT: Herein, we demonstrate that the activity of a hydrogen-bond-donating (HBD) catalyst embedded within a coordination framework can be allosterically regulated in situ by controlling oligomerization via simple changes in coordination chemistry at distal Pt(II) nodes. Using the halide-induced ligand rearrangement reaction (HILR), a heteroligated Pt(II) triple-decker complex, which contains a catalytically active diphenylene squaramide moiety and two hydrogen-bond-accepting (HBA) ester moieties, was synthesized. The HBD and HBA moieties were functionalized with hemilabile ligands of differing chelating strengths, allowing one to assemble them around Pt(II) nodes in a heteroligated fashion. Due to the hemilabile nature of the ligands, the resulting complex can be interconverted between a flexible, semiopen state and a rigid, fully closed state in situ and reversibly. FT-IR spectroscopy, (1)H DOSY, and (1)H NMR spectroscopy titration studies were used to demonstrate that, in the semiopen state, intermolecular hydrogen-bonding between the HBD and HBA moieties drives oligomerization of the complex and prevents substrate recognition by the catalyst. In the rigid, fully closed state, these interactions are prevented by steric and geometric constraints. Thus, the diphenylene squaramide moiety is able to catalyze a Friedel-Crafts reaction in the fully closed state, while the semiopen state shows no reactivity. This work demonstrates that controlling catalytic activity by regulating aggregation through supramolecular conformational changes, a common approach in Nature, can be applied to man-made catalytic frameworks that are relevant to materials synthesis, as well as the detection and amplification of small molecules.
    Journal of the American Chemical Society 11/2014; · 11.44 Impact Factor
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    ABSTRACT: Precise control of molecular assembly is a challenging goal facing supramolecular chemists. Herein, we report the highly specific assembly of a range of supramolecular nanotubes from the enantiomeric triangular naphthalenediimide-based macrocycles (RRRRRR)- and (SSSSSS)-NDI-Δ and a class of similar solvents—namely, the 1,2-dihalo-ethanes and -ethenes (DXEs). Three kinds of supramolecular nanotubes are formed from the columnar stacking of NDI-Δ units with a 60° mutual rotation angle as a result of cooperative [C–H•••O] interactions, directing interactions of the [X•••X]-bonded DXE chains inside the nanotubes, and lateral [X•••π] or [π•••π] interactions. They include (i) semiflexible infinite supramolecular nanotubes formed in the gel state from NDI-Δ and (E)-1,2-dichloroethene (DCE), (ii) rigid infinite non-helical supramolecular nanotubes produced in the solid state from NDI-Δ and BrCH2CH2Br, ClCH2CH2Br, and ClCH2CH2I, and (iii) a pair of rigid tetrameric, enantiomeric single-handed (P)- and (M)-helical supramolecular nanotubes formed in the solid state during crystallization from the corresponding (RRRRRR)- and (SSSSSS)-NDI-Δ with ClCH2CH2Cl. In case (i), only the electron-rich C=C double bond of (E)-DCE facilitates the gelation of NDI-Δ. In cases (ii) and (iii), the lengths of anti-DXEs determine the translation of the chirality of NDI-Δ into the helicity of nanotubes. Only ClCH2CH2Cl induces single-handed helicity into these nanotubes. The subtle interplay of noncovalent bonding interactions, resulting from the tiny variations involving the DXE guests, is responsible for the diverse and highly specific assembly of NDI-Δ. This research highlights the critical role that guests play in constructing assembled superstructures of hosts and offers a novel approach to creating supramolecular nanotubes.
    Journal of the American Chemical Society 10/2014; 136(47):16651–16660. · 11.44 Impact Factor
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    ABSTRACT: If a solution of DNA-coated nanoparticles is allowed to crystallize, the thermodynamic structure can be predicted by a set of structural design rules analogous to Pauling's rules for ionic crystallization. The details of the crystallization process, however, have proved more difficult to characterize as they depend on a complex interplay of many factors. Here, we report that this crystallization process is dictated by the individual DNA bonds and that the effect of changing structural or environmental conditions can be understood by considering the effect of these parameters on free oligonucleotides. Specifically, we observed the reorganization of nanoparticle superlattices using time-resolved synchrotron small-angle X-ray scattering in systems with different DNA sequences, salt concentrations, and densities of DNA linkers on the surface of the nanoparticles. The agreement between bulk crystallization and the behavior of free oligonucleotides may bear important consequences for constructing novel classes of crystals and incorporating new interparticle bonds in a rational manner.
    Proceedings of the National Academy of Sciences 10/2014; · 9.81 Impact Factor
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    ABSTRACT: A novel, apertureless, cantilever-free pen array can be used for dual scanning photochemical and molecular printing. Serial writing with light is enabled by combining self-focusing pyramidal pens with an opaque backing between pens. The elastomeric pens also afford force-tuned illumination and simultaneous delivery of materials and optical energy. These attributes make the technique a promising candidate for maskless high-resolution photopatterning and combinatorial chemistry.
    Small 10/2014; · 7.51 Impact Factor
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    ABSTRACT: The evolution of crystallite size and microstrain in DNA-mediated nanoparticle superlattices is dictated by annealing temperature and the flexibility of interparticle bonds. This work addresses a major challenge in synthesizing optical metamaterials based upon noble metal nanoparticles by enabling the crystallization of large nanoparticles (100 nm diameter) at high volume fractions (34% metal).
    Advanced Materials 09/2014; · 15.41 Impact Factor
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    ABSTRACT: Herein, we describe a rapid, divergent method for using spherical nucleic acids (SNAs) as a universal platform for attaching RNA to DNA-modified nanoparticles using enzyme-mediated techniques. This approach provides a sequence-specific method for the covalent attachment of one or more in vitro transcribed RNAs to a universal SNA scaffold, regardless of RNA sequence. The RNA-nanoparticle constructs are shown to effectively knock down two different gene targets using a single, dual-ligated nanoparticle construct.
    ACS Nano 08/2014; · 12.03 Impact Factor
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    ABSTRACT: Many nanoparticle adsorption processes are dictated by the collective interactions of surface-bound ligands. These adsorption processes define how nanoparticles interact with biological systems and enable the assembly of nanoparticle-based materials and devices. Herein, we present an approach for quantifying nanoparticle adsorption thermodynamics in a manner that satisfies the assumptions of the Langmuir model. Using this approach, we study the DNA-mediated adsorption of polyvalent anisotropic nanoparticles on surfaces and explore how deviations from model assumptions influence adsorption thermodynamics. Importantly, when combined with a solution-based van’t Hoff analysis, we find that polyvalency plays a more important role as the individual interactions become weaker. Furthermore, we find that the free energy of anisotropic nanoparticle adsorption is consistent across multiple shapes and sizes of nanoparticles based on the surface area of the interacting facet.
    Angewandte Chemie International Edition 07/2014; · 11.34 Impact Factor
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    ABSTRACT: A biomimetic, ion-regulated molecular receptor was synthesized via the Weak-Link Approach (WLA). This structure features both a calix[4]arene moiety which serves as a molecular recognition unit and an activity regulator composed of hemilabile phosphine alkyl thioether ligands (P,S) chelated to a Pt(II) center. The host-guest properties of the ion-regulated receptor were found to be highly dependent upon the coordination of the Pt(II) center, which is controlled through the reversible coordination of small molecule effectors. The environment at the regulatory site dictates the charge and the structural conformation of the entire assembly resulting in three accessible binding configurations: one closed, inactive state and two open, active states. One of the active states, the semiopen state, recognizes a neutral guest molecule, while the other, the fully open state, recognizes a cationic guest molecule. Job plots and (1)H NMR spectroscopy titrations were used to study the formation of these inclusion complexes, the receptor binding modes, and the receptor binding affinities (Ka) in solution. Single crystal X-ray diffraction studies provided insight into the solid-state structures of the receptor when complexed with each guest molecule. The dipole moments and electrostatic potential maps of the structures were generated via DFT calculations at the B97D/LANL2DZ level of theory. Finally, we describe the reversible capture and release of guests by switching the receptor between the closed and semiopen configurations via elemental anion and small molecule effectors.
    Journal of the American Chemical Society 07/2014; · 11.44 Impact Factor
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    ABSTRACT: A novel class of metal-free spherical nucleic acid nanostructures was synthesized from readily available starting components. These particles consist of 30 nm liposomal cores, composed of an FDA-approved 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipid monomer. The surface of the liposomes was functionalized with DNA strands modified with a tocopherol tail that intercalates into the phospholipid layer of the liposomal core via hydrophobic interactions. The spherical nucleic acid architecture not only stabilizes these constructs but also facilitates cellular internalization and gene regulation in SKOV-3 cells.
    Journal of the American Chemical Society 07/2014; · 11.44 Impact Factor

Publication Stats

50k Citations
6,193.27 Total Impact Points

Institutions

  • 1995–2015
    • Northwestern University
      • • Department of Materials Science and Engineering
      • • Department of Chemistry
      Evanston, Illinois, United States
  • 2004–2014
    • Northwest University
      Evanston, Illinois, United States
  • 2011
    • Washington University in St. Louis
      • Department of Biomedical Engineering
      San Luis, Missouri, United States
    • 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 Toronto
      Toronto, Ontario, Canada
  • 2009
    • Nanyang Technological University
      • School of Chemical and Biomedical Engineering
      Singapore, Singapore
  • 2003–2009
    • University of Illinois, Urbana-Champaign
      • • Department of Bioengineering
      • • Department of Electrical and Computer Engineering
      Urbana, IL, United States
    • The Scripps Research Institute
      La Jolla, California, United States
  • 2008
    • University of Alberta
      • Department of Chemistry
      Edmonton, Alberta, Canada
  • 2007
    • Johns Hopkins University
      • Department of Chemistry
      Baltimore, Maryland, United States
  • 2006
    • Yonsei University
      • Department of Chemistry
      Seoul, Seoul, South Korea
    • Sogang University
      • Department of Chemical and Biomolecular Engineering
      Sŏul, Seoul, South Korea
    • International Council on Nanotechnology
      Evanston, Illinois, United States
  • 1987–1990
    • University of Delaware
      • Department of Chemistry and Biochemistry
      Newark, DE, 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