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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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Related in: MedlinePlus

Retention in the circulation of largeinjected oligoclusters. TEMimage of renal glomerulus after intra-arterial injection of oligoclustersmade with a delay time of 405 s. Inset: A higher magnification ofoligoclusters present in the plasma. GBM, glomerular basement membrane;FE, fenestrated endothelium; PFP, podocyte foot process. Note thatnone of the oligoclusters have penetrated the basement membrane andthat, despite their large size, they do not aggregate in the plasma.The dark spot in the image at 4 o’clock from “GBM”is a camera artifact, not an oligocluster.
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fig8: Retention in the circulation of largeinjected oligoclusters. TEMimage of renal glomerulus after intra-arterial injection of oligoclustersmade with a delay time of 405 s. Inset: A higher magnification ofoligoclusters present in the plasma. GBM, glomerular basement membrane;FE, fenestrated endothelium; PFP, podocyte foot process. Note thatnone of the oligoclusters have penetrated the basement membrane andthat, despite their large size, they do not aggregate in the plasma.The dark spot in the image at 4 o’clock from “GBM”is a camera artifact, not an oligocluster.

Mentions: In theother direction, the sizes of the oligoclusters can be madeso large that they cannot pass through basement membranes but arestill not aggregated in the bloodstream. Figure 8 illustrates this capability by showing that oligoclusters made witha 405 s delay time are largely excluded from the basement membraneof the renal glomerulus, although they are clearly well dispersedand free from aggregation in the plasma. Because the number of particlesper image is about 100 times greater than has previously been possible,and many images can be examined and the data combined, it should bepossible to detect and quantify permeation into the GBM at levelsas low as 0.01 times that in plasma.


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)

Retention in the circulation of largeinjected oligoclusters. TEMimage of renal glomerulus after intra-arterial injection of oligoclustersmade with a delay time of 405 s. Inset: A higher magnification ofoligoclusters present in the plasma. GBM, glomerular basement membrane;FE, fenestrated endothelium; PFP, podocyte foot process. Note thatnone of the oligoclusters have penetrated the basement membrane andthat, despite their large size, they do not aggregate in the plasma.The dark spot in the image at 4 o’clock from “GBM”is a camera artifact, not an oligocluster.
© Copyright Policy
Related In: Results  -  Collection

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

fig8: Retention in the circulation of largeinjected oligoclusters. TEMimage of renal glomerulus after intra-arterial injection of oligoclustersmade with a delay time of 405 s. Inset: A higher magnification ofoligoclusters present in the plasma. GBM, glomerular basement membrane;FE, fenestrated endothelium; PFP, podocyte foot process. Note thatnone of the oligoclusters have penetrated the basement membrane andthat, despite their large size, they do not aggregate in the plasma.The dark spot in the image at 4 o’clock from “GBM”is a camera artifact, not an oligocluster.
Mentions: In theother direction, the sizes of the oligoclusters can be madeso large that they cannot pass through basement membranes but arestill not aggregated in the bloodstream. Figure 8 illustrates this capability by showing that oligoclusters made witha 405 s delay time are largely excluded from the basement membraneof the renal glomerulus, although they are clearly well dispersedand free from aggregation in the plasma. Because the number of particlesper image is about 100 times greater than has previously been possible,and many images can be examined and the data combined, it should bepossible to detect and quantify permeation into the GBM at levelsas low as 0.01 times that in plasma.

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