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Stable oligomeric clusters of gold nanoparticles: preparation, size distribution, derivatization, and physical and biological properties.

Smithies O, Lawrence M, Testen A, Horne LP, Wilder J, Altenburg M, Bleasdale B, Maeda N, Koklic T - Langmuir (2014)

Bottom Line: The crude oligocluster preparations have narrow size distributions, and for most purposes do not require fractionation.The oligoclusters do not aggregate after ∼300-fold centrifugal-filter concentration, and at this high concentration are easily derivatized with a variety of thiol-containing reagents.Unlike conventional glutathione-capped nanoparticles of comparable gold content, large oligoclusters derivatized with glutathione do not aggregate at high concentrations in phosphate-buffered saline (PBS) or in the circulation when injected into mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, and ‡Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.

ABSTRACT
Reducing dilute aqueous HAuCl4 with NaSCN under alkaline conditions produces 2-3 nm diameter yellow nanoparticles without the addition of extraneous capping agents. We here describe two very simple methods for producing highly stable oligomeric grape-like clusters (oligoclusters) of these small nanoparticles. The oligoclusters have well-controlled diameters ranging from ∼5 to ∼30 nm, depending mainly on the number of subunits in the cluster. Our first ["delay-time"] method controls the size of the oligoclusters by varying from seconds to hours the delay time between making the HAuCl4 alkaline and adding the reducing agent, NaSCN. Our second ["add-on"] method controls size by using yellow nanoparticles as seeds onto which varying amounts of gold derived from "hydroxylated gold", Na(+)[Au(OH4-x)Clx](-), are added-on catalytically in the presence of NaSCN. Possible reaction mechanisms and a simple kinetic model fitting the data are discussed. The crude oligocluster preparations have narrow size distributions, and for most purposes do not require fractionation. The oligoclusters do not aggregate after ∼300-fold centrifugal-filter concentration, and at this high concentration are easily derivatized with a variety of thiol-containing reagents. This allows rare or expensive derivatizing reagents to be used economically. Unlike conventional glutathione-capped nanoparticles of comparable gold content, large oligoclusters derivatized with glutathione do not aggregate at high concentrations in phosphate-buffered saline (PBS) or in the circulation when injected into mice. Mice receiving them intravenously show no visible signs of distress. Their sizes can be made small enough to allow their excretion in the urine or large enough to prevent them from crossing capillary basement membranes. They are directly visible in electron micrographs without enhancement, and can model the biological fate of protein-like macromolecules with controlled sizes and charges. The ease of derivatizing the oligoclusters makes them potentially useful for presenting pharmacological agents to different tissues while controlling escape of the reagents from the circulation.

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High-resolution transmission electronmicroscopy. (A) An imageof several oligoclusters having 3 or 4 subunits in a sample preparedby the add-on method with a 1:1 mixture of 20 s seeds and HG. Thearrow points to a subunit shown at higher magnification in panel E.(B) An image of a 4 subunit oligocluster in a sample prepared by theadd-on method with a 1:1 mixture of 30 s seeds and HG. (C) An imageof a 5 subunit oligocluster in a sample prepared by the add-on methodwith a 1:1 mixture of 135 s seeds and HG. An enlarged view of thesubunit indicated by the arrowhead in panel A. (D) A very large oligoclusterhaving about 50 subunits in a sample prepared by reducing HG in theabsence of any seeds. (E) A higher magnification of the subunit in(A) indicated with a black arrow. The white arrows highlight a discontinuityin the crystal lattice, suggesting that the subunit is a twinned crystalformed by adding elemental gold onto a pre-existing particle. (F)A single nanoparticle in a sample prepared by the add-on method witha 1:1 mixture of 20 s seeds and HG.
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fig6: High-resolution transmission electronmicroscopy. (A) An imageof several oligoclusters having 3 or 4 subunits in a sample preparedby the add-on method with a 1:1 mixture of 20 s seeds and HG. Thearrow points to a subunit shown at higher magnification in panel E.(B) An image of a 4 subunit oligocluster in a sample prepared by theadd-on method with a 1:1 mixture of 30 s seeds and HG. (C) An imageof a 5 subunit oligocluster in a sample prepared by the add-on methodwith a 1:1 mixture of 135 s seeds and HG. An enlarged view of thesubunit indicated by the arrowhead in panel A. (D) A very large oligoclusterhaving about 50 subunits in a sample prepared by reducing HG in theabsence of any seeds. (E) A higher magnification of the subunit in(A) indicated with a black arrow. The white arrows highlight a discontinuityin the crystal lattice, suggesting that the subunit is a twinned crystalformed by adding elemental gold onto a pre-existing particle. (F)A single nanoparticle in a sample prepared by the add-on method witha 1:1 mixture of 20 s seeds and HG.

Mentions: To better understand the add-on process, we obtained high-resolutiontransmission electron micrographs of clusters and subunits resultingfrom experiments in which the NaSCN reduction was carried out withor without seeds with or without hydrolyzed gold (HG). Figure 6A shows an image of several oligoclusters with 3or 4 subunits when the add-on reaction was carried out with a 1:1mixtures of HG and 20 s delay-time seeds. Note the wide separationof the subunits. Nothing sufficiently electron dense to be visualizedin the TEM image is apparent between the subunits, although the remarkablestability of the oligoclusters suggests that some covalently bondedpolymeric chain is linking them.


Stable oligomeric clusters of gold nanoparticles: preparation, size distribution, derivatization, and physical and biological properties.

Smithies O, Lawrence M, Testen A, Horne LP, Wilder J, Altenburg M, Bleasdale B, Maeda N, Koklic T - Langmuir (2014)

High-resolution transmission electronmicroscopy. (A) An imageof several oligoclusters having 3 or 4 subunits in a sample preparedby the add-on method with a 1:1 mixture of 20 s seeds and HG. Thearrow points to a subunit shown at higher magnification in panel E.(B) An image of a 4 subunit oligocluster in a sample prepared by theadd-on method with a 1:1 mixture of 30 s seeds and HG. (C) An imageof a 5 subunit oligocluster in a sample prepared by the add-on methodwith a 1:1 mixture of 135 s seeds and HG. An enlarged view of thesubunit indicated by the arrowhead in panel A. (D) A very large oligoclusterhaving about 50 subunits in a sample prepared by reducing HG in theabsence of any seeds. (E) A higher magnification of the subunit in(A) indicated with a black arrow. The white arrows highlight a discontinuityin the crystal lattice, suggesting that the subunit is a twinned crystalformed by adding elemental gold onto a pre-existing particle. (F)A single nanoparticle in a sample prepared by the add-on method witha 1:1 mixture of 20 s seeds and HG.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230385&req=5

fig6: High-resolution transmission electronmicroscopy. (A) An imageof several oligoclusters having 3 or 4 subunits in a sample preparedby the add-on method with a 1:1 mixture of 20 s seeds and HG. Thearrow points to a subunit shown at higher magnification in panel E.(B) An image of a 4 subunit oligocluster in a sample prepared by theadd-on method with a 1:1 mixture of 30 s seeds and HG. (C) An imageof a 5 subunit oligocluster in a sample prepared by the add-on methodwith a 1:1 mixture of 135 s seeds and HG. An enlarged view of thesubunit indicated by the arrowhead in panel A. (D) A very large oligoclusterhaving about 50 subunits in a sample prepared by reducing HG in theabsence of any seeds. (E) A higher magnification of the subunit in(A) indicated with a black arrow. The white arrows highlight a discontinuityin the crystal lattice, suggesting that the subunit is a twinned crystalformed by adding elemental gold onto a pre-existing particle. (F)A single nanoparticle in a sample prepared by the add-on method witha 1:1 mixture of 20 s seeds and HG.
Mentions: To better understand the add-on process, we obtained high-resolutiontransmission electron micrographs of clusters and subunits resultingfrom experiments in which the NaSCN reduction was carried out withor without seeds with or without hydrolyzed gold (HG). Figure 6A shows an image of several oligoclusters with 3or 4 subunits when the add-on reaction was carried out with a 1:1mixtures of HG and 20 s delay-time seeds. Note the wide separationof the subunits. Nothing sufficiently electron dense to be visualizedin the TEM image is apparent between the subunits, although the remarkablestability of the oligoclusters suggests that some covalently bondedpolymeric chain is linking them.

Bottom Line: The crude oligocluster preparations have narrow size distributions, and for most purposes do not require fractionation.The oligoclusters do not aggregate after ∼300-fold centrifugal-filter concentration, and at this high concentration are easily derivatized with a variety of thiol-containing reagents.Unlike conventional glutathione-capped nanoparticles of comparable gold content, large oligoclusters derivatized with glutathione do not aggregate at high concentrations in phosphate-buffered saline (PBS) or in the circulation when injected into mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, and ‡Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.

ABSTRACT
Reducing dilute aqueous HAuCl4 with NaSCN under alkaline conditions produces 2-3 nm diameter yellow nanoparticles without the addition of extraneous capping agents. We here describe two very simple methods for producing highly stable oligomeric grape-like clusters (oligoclusters) of these small nanoparticles. The oligoclusters have well-controlled diameters ranging from ∼5 to ∼30 nm, depending mainly on the number of subunits in the cluster. Our first ["delay-time"] method controls the size of the oligoclusters by varying from seconds to hours the delay time between making the HAuCl4 alkaline and adding the reducing agent, NaSCN. Our second ["add-on"] method controls size by using yellow nanoparticles as seeds onto which varying amounts of gold derived from "hydroxylated gold", Na(+)[Au(OH4-x)Clx](-), are added-on catalytically in the presence of NaSCN. Possible reaction mechanisms and a simple kinetic model fitting the data are discussed. The crude oligocluster preparations have narrow size distributions, and for most purposes do not require fractionation. The oligoclusters do not aggregate after ∼300-fold centrifugal-filter concentration, and at this high concentration are easily derivatized with a variety of thiol-containing reagents. This allows rare or expensive derivatizing reagents to be used economically. Unlike conventional glutathione-capped nanoparticles of comparable gold content, large oligoclusters derivatized with glutathione do not aggregate at high concentrations in phosphate-buffered saline (PBS) or in the circulation when injected into mice. Mice receiving them intravenously show no visible signs of distress. Their sizes can be made small enough to allow their excretion in the urine or large enough to prevent them from crossing capillary basement membranes. They are directly visible in electron micrographs without enhancement, and can model the biological fate of protein-like macromolecules with controlled sizes and charges. The ease of derivatizing the oligoclusters makes them potentially useful for presenting pharmacological agents to different tissues while controlling escape of the reagents from the circulation.

Show MeSH
Related in: MedlinePlus