Polyvalent DNA gold nanoparticles

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Polyvalent DNA gold nanoparticles, now more commonly referred to as spherical nucleic acids, [1] (Fig. 1) are colloidal gold particles densely modified with short (typically ~30-mer or less), highly oriented, synthetic DNA strands. They were invented by Chad Mirkin et al. at Northwestern University in 1996. [2] Paul Alivisatos et al. at the University of California, Berkeley introduced a related monovalent structure the same year. [3] Due to the strong interaction between gold and thiols (-SH), the first polyvalent DNA gold nanoparticles were obtained by capping the gold nanoparticles with a dense monolayer of thiol-modified DNA. The dense packing and negative charge of the phosphate backbones of DNA orients it into solution (like a “koosh ball”) with a footprint that is dependent on factors including the particle size and radius of curvature. [4]

Contents

Figure 1. Schematic of a polyvalent DNA gold nanoparticle. DNA-AuNP0022.jpg
Figure 1. Schematic of a polyvalent DNA gold nanoparticle.

Properties and Applications

The three-dimensional structure of the DNA shell imparts upon these conjugates novel chemical, physical, and biological properties that are not associated with the same sequences of linear DNA free in solution. For example, SNA-gold nanoparticle conjugates have been shown to exhibit increased uptake into cells compared to their linear counterparts. [5] Furthermore, when hybridized to a nucleic acid “reporter” strand containing a fluorophore probe, these polyvalent nanoparticles can be used as intracellular probes to detect specific mRNA sequences within single living cells. [6]

Polyvalent DNA gold nanoparticles have also spurred significant advances in the field of materials science and engineering. When one set of polyvalent DNA gold nanoparticles is combined with another that is functionalized with complementary DNA sequences, the particles assemble via DNA hybridization interactions. These nanoparticles can be used to prepare a wide range of colloidal crystals with sub-nanometer level precision (Fig. 2). [7] Polyvalent DNA gold nanoparticles also form the basis for a new field of chemistry where a particle can be viewed as an “atom” and the DNA as “bonds” to make higher-order materials. [8]

Figure 2. Examples of nanoparticle superlattices that can be synthesized based on SNA-nanoparticle conjugates. Different structures can be accessed in part by changing the properties of the DNA shell. The structures (left) are verified using small angle X-ray scattering (middle) and electron microscopy (right). Programmable-Nanomaterials-fig2-new.jpg
Figure 2. Examples of nanoparticle superlattices that can be synthesized based on SNA-nanoparticle conjugates. Different structures can be accessed in part by changing the properties of the DNA shell. The structures (left) are verified using small angle X-ray scattering (middle) and electron microscopy (right).

Due to cooperative effects stemming from polyvalency (chemistry), a polyvalent SNA-nanoparticle conjugate binds tighter to a complementary free linear strand than does the same sequence of DNA free in solution. [9] This finding has paved the way to the development of various detection methodologies based on this class of nanoparticles. [10] [11]

Synthesis and Functionalization

Gold nanoparticles can be purchased or synthesized via a variety of methods. [12] Several strategies exist for functionalizing gold nanoparticles with single-stranded DNA; one of the most commonly utilized strategies involves introducing thiol-terminated DNA to a solution of gold nanoparticles and gradually increasing the concentration of a salt, like NaCl. The addition of NaCl reduces repulsive forces between like-charged DNA strands (negative) so that they pack densely on nanoparticle surfaces. A typical procedure for preparing polyvalent DNA gold nanoparticles is outlined briefly below: [13]

  1. Reduce dithiol moieties by adding 0.1 M dithiothreitol (DTT) in 0.18 M phosphate buffer (PB) (pH=8) to lyophilized thiolated DNA and letting the solution sit for at least 1 hour.
  2. Purify the DNA using a NAP-5 column.
  3. Add the purified DNA to the gold nanoparticles at a concentration of 1 OD/mL.
  4. Bring the concentration of sodium dodecyl sulfate (SDS) and PB to final concentrations of 0.01% and 0.01 M, respectively.
  5. After 20 minutes, bring the concentration of NaCl to 0.05 M using a 2 M NaCl/0.01 M PB stock solution while maintaining 0.01% SDS. Incubate for 20 minutes.
  6. Repeat step 5 to increase the concentration of NaCl by 0.05 M.
  7. Increase the NaCl concentration at increments of 0.1 M until a final concentration of 1 M is reached using 20-minute incubation periods.
  8. Incubate overnight.
  9. Centrifuge the gold nanoparticle solution (the functionalized particles will collect at the bottom of the reaction vessel), remove the supernatant, and resuspend the particles in a 0.1% SDS solution.
  10. Repeat step 9 four times to complete the purification of the functionalized particles from any excess free DNA in solution.

Related Research Articles

Sodium dodecyl sulfate (SDS) or sodium lauryl sulfate (SLS), sometimes written sodium laurilsulfate, is a synthetic organic compound with the formula CH3(CH2)11SO4Na. It is an anionic surfactant used in many cleaning and hygiene products. This molecule is an organosulfate and a salt. It consists of a 12-carbon tail attached to a sulfate group, that is, it is the sodium salt of dodecyl hydrogen sulfate, the ester of dodecyl alcohol and sulfuric acid. Its hydrocarbon tail combined with a polar "headgroup" give the compound amphiphilic properties and so make it useful as a detergent. Also derived as a component of mixtures produced from inexpensive coconut and palm oils, SDS is a common component of many domestic cleaning, personal hygiene and cosmetic, pharmaceutical, and food products, as well as of industrial and commercial cleaning and product formulations.

Nanoshell

A nanoshell, or rather a nanoshell plasmon, is a type of spherical nanoparticle consisting of a dielectric core which is covered by a thin metallic shell. These nanoshells involve a quasiparticle called a plasmon which is a collective excitation or quantum plasma oscillation where the electrons simultaneously oscillate with respect to all the ions.

Colloidal gold

Colloidal gold is a sol or colloidal suspension of nanoparticles of gold in a fluid, usually water. The colloid is usually either an intense red colour or blue/purple . Due to their optical, electronic, and molecular-recognition properties, gold nanoparticles are the subject of substantial research, with many potential or promised applications in a wide variety of areas, including electron microscopy, electronics, nanotechnology, materials science, and biomedicine.

Nanoparticle Particle with size less than 100 nm

A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 100 nm in only two directions. At the lowest range, metal particles smaller than 1 nm are usually called atom clusters instead.

Self-assembled monolayer

Self-assembled monolayers (SAM) of organic molecules are molecular assemblies formed spontaneously on surfaces by adsorption and are organized into more or less large ordered domains. In some cases molecules that form the monolayer do not interact strongly with the substrate. This is the case for instance of the two-dimensional supramolecular networks of e.g. perylenetetracarboxylic dianhydride (PTCDA) on gold or of e.g. porphyrins on highly oriented pyrolitic graphite (HOPG). In other cases the molecules possess a head group that has a strong affinity to the substrate and anchors the molecule to it. Such a SAM consisting of a head group, tail and functional end group is depicted in Figure 1. Common head groups include thiols, silanes, phosphonates, etc.

Dip-pen nanolithography Scanning probe lithographic technique

Dip pen nanolithography (DPN) is a scanning probe lithography technique where an atomic force microscope (AFM) tip is used to create patterns directly on a range of substances with a variety of inks. A common example of this technique is exemplified by the use of alkane thiolates to imprint onto a gold surface. This technique allows surface patterning on scales of under 100 nanometers. DPN is the nanotechnology analog of the dip pen, where the tip of an atomic force microscope cantilever acts as a "pen," which is coated with a chemical compound or mixture acting as an "ink," and put in contact with a substrate, the "paper."

Cetrimonium bromide

Cetrimonium bromide ([(C16H33)N(CH3)3]Br; cetyltrimethylammonium bromide; hexadecyltrimethylammonium bromide; CTAB) is a quaternary ammonium surfactant.

Scanning probe lithography (SPL) describes a set of nanolithographic methods to pattern material on the nanoscale using scanning probes. It is a direct-write, mask-less approach which bypasses the diffraction limit and can reach resolutions below 10 nm. It is considered an alternative lithographic technology often used in academic and research environments. The term scanning probe lithography was coined after the first patterning experiments with scanning probe microscopes (SPM) in the late 1980s.

Chloroauric acid

Chloroauric acid refers to inorganic compounds with the chemical formula HAuCl
4·(H
2O)
x. Both the trihydrate and tetrahydrate are known. Both are orange-yellow solids consisting of the planar [AuCl4]− anion. Often chloroauric acid is handled as a solution, such as those obtained by dissolution of gold in aqua regia. These solutions can be converted to other gold complexes or reduced to metallic gold or gold nanoparticles.

Janus particles

Janus particles are special types of nanoparticles or microparticles whose surfaces have two or more distinct physical properties. This unique surface of Janus particles allows two different types of chemistry to occur on the same particle. The simplest case of a Janus particle is achieved by dividing the particle into two distinct parts, each of them either made of a different material, or bearing different functional groups. For example, a Janus particle may have one-half of its surface composed of hydrophilic groups and the other half hydrophobic groups, the particles might have two surfaces of different color, fluorescence, or magnetic properties. This gives these particles unique properties related to their asymmetric structure and/or functionalization.

Platinum nanoparticle

Platinum nanoparticles are usually in the form of a suspension or colloid of nanoparticles of platinum in a fluid, usually water. A colloid is technically defined as a stable dispersion of particles in a fluid medium.

Silver nanoparticle Ultrafine particles of silver between 1 nm and 100 nm in size

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Spherical nucleic acid

Spherical nucleic acids (SNAs) are nanostructures that consist of a densely packed, highly oriented arrangement of linear nucleic acids in a three-dimensional, spherical geometry. This novel three-dimensional architecture is responsible for many of the SNA's novel chemical, biological, and physical properties that make it useful in biomedicine and materials synthesis. SNAs were first introduced in 1996 by Chad Mirkin’s group at Northwestern University.

Self-assembly of nanoparticles

Nanoparticles are classified as having at least one of three dimensions be in the range of 1-100 nm. The small size of nanoparticles allows them to have unique characteristics which may not be possible on the macro-scale. Self-assembly is the spontaneous organization of smaller subunits to form larger, well-organized patterns. For nanoparticles, this spontaneous assembly is a consequence of interactions between the particles aimed at achieving a thermodynamic equilibrium and reducing the system’s free energy. The thermodynamics definition of self-assembly was introduced by Nicholas A. Kotov. He describes self-assembly as a process where components of the system acquire non-random spatial distribution with respect to each other and the boundaries of the system. This definition allows one to account for mass and energy fluxes taking place in the self-assembly processes.

Thiolate-protected gold cluster

Thiolate-protected gold clusters are a type of ligand-protected metal cluster, synthesized from gold ions and thin layer compounds that play a special role in cluster physics because of their unique stability and electronic properties. They are considered to be stable compounds.

Metal nanoclusters consist of a small number of atoms, at most in the tens. These nanoclusters can be composed either of a single or of multiple elements, and typically measure less than 2 nm. Such nanoclusters exhibit attractive electronic, optical, and chemical properties compared to their larger counterparts. Materials can be categorized into three different regimes, namely bulk, nanoparticles or nanostructures and atomic clusters. Bulk metals are electrical conductors and good optical reflectors, while metal nanoparticles display intense colors due to surface plasmon resonance. When the size of metal nanoclusters is further reduced, to 1 nm or less, in other words to just a few atoms, the band structure becomes discontinuous and breaks down into discrete energy levels, somewhat similar to the energy levels of molecules.

Gold nanoparticles in chemotherapy

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So-Jung Park 박소정(朴昭靜) is a Professor of Chemistry at Ewha Womans University. Her research considers the self-assembly of nanoparticles and functional molecules for biomedical and optoelectronic devices. She serves as Associate Editor of ACS Applied Materials & Interfaces and Nanoscale.

References

  1. ↑ Cutler, J. I.; Auyeung, E.; Mirkin, C. A. “Spherical Nucleic Acids,” Journal of the American Chemical Society, 2012, 134, 1376–1391, doi: 10.1021/ja209351u.
  2. ↑ Mirkin, C. A.; Letsinger, R. L.; Mucic, R. C; Storhoff, J. J. “A DNA-based method for rationally assembling nanoparticles into macroscopic materials,” Nature, 1996, 382, 607-609, doi: 10.1038/382607a0.
  3. ↑ Alivisatos, A. P.; Johnsson, K. P.; Peng, X.; Wilson, T. E.; Loweth, C. J.; Bruchez, M. P., Jr.; Schultz, P. G. "Organization of 'nanocrystal molecules' using DNA," Nature, 1996, 382, 609–611. doi: 10.1038/382609a0
  4. ↑ Hill, H. D.; Millstone, J. E.; Banholzer, M. J.; Mirkin, C. A. “The Role Radius of Curvature Plays in Thiolated Oligonucleotide Loading on Gold Nanoparticles,” ACS Nano, 2009, 3, 418-424. doi: 10.1021/nn800726e.
  5. ↑ Rosi, N. L.; Giljohann, D. A.; Thaxton, C. S.; Lytton-Jean, A. K. R.; Han, M. S.; Mirkin, C. A. “Oligonucleotide-Modified Gold Nanoparticles for Intracellular Gene Regulation,” Science, 2006, 312, 1027-1030. doi: 10.1126/science.1125559.
  6. ↑ 305. Seferos, D. S.; Giljohann, D. A.; Hill, H. D.; Prigodich, A. E.; Mirkin, C. A. “Nano-flares: Probes for Transfection and mRNA Detection in Living Cells,” Journal of the American Chemical Society, 2007, 129, 15477-15479. doi: 10.1021/ja0776529.
  7. ↑ Macfarlane, R. J.; Lee, B.; Jones, M. R.; Harris, N.; Schatz, G. C.; Mirkin, C. A. “Nanoparticle Superlattice Engineering with DNA,” Science, 2011, 334, 204-208. doi: 10.1126/science.1210493.
  8. ↑ Jones, M. R.; Seeman, N. C.; Mirkin, C. A. “Programmable Materials and the Nature of the DNA Bond,” Science, 2015, 347, 1260901, doi: 10.1126/science.1260901.
  9. ↑ Lytton-Jean, A. K. R.; Mirkin, C. A. “A Thermodynamic Investigation into the Binding Properties of DNA Functionalized Gold Nanoparticle Probes and Molecular Fluorophore Probes,” Journal of the American Chemical Society, 2005, 127, 12754-12755. doi:10.1021/ja052255o.
  10. ↑ Taton, T. A.; Mirkin, C. A.; Letsinger, R. L. “Scanometric DNA Array Detection with Nanoparticle Probes,” Science, 2000, 289, 1757-1760. doi: 10.1126/science.289.5485.1757.
  11. ↑ Nam, J.-M.; Thaxton, C. S.; Mirkin, C. A. “Nanoparticle-Based Bio-Bar Codes for the Ultrasensitive Detection of Proteins,” Science, 2003, 301, 1884-1886. doi: 10.1126/science.1088755.
  12. ↑ Liu, B.; Liu, J. “Methods for preparing DNA-functionalized gold nanoparticles, a key reagent of bioanalytical chemistry,” Analytical Methods, 2017, 9, 2633-2643. doi: 10.1039/c7ay00368d.
  13. ↑ Hurst, S. J.; Lytton-Jean, A. K. R.; Mirkin, C. A. "Maximizing DNA Loading on a Range of Gold Nanoparticle Sizes," Analytical Chemistry, 2006, 78, 8313–8318. doi:10.1021/ac0613582.
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