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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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Polyacrylamide gradientgel electrophoresis and TEM images of theproducts of the add-on procedure with different mixtures of seedsand HG. (A) Lane 1, 20 s seeds without HG (no HG); lanes 2–5,the products obtained after add-on reactions with 20 s seeds in thepresence of 1/2×, 1×, 2×, and 4× HG. (B) Lane1, the products of the add-on reaction with HG in the absence of seeds(No Seeds); lanes 2–4, 5–7, and 8–10, the productsobtained with 5, 20, and 30 s seeds after add-on reactions with noHG, 1×, and 2× HG. Note that the overall sizes of the oligoclustersincrease in proportion both to the sizes of the seeds and to the amountof HG. (C) TEM images of 30 s seeds without HG (no HG) and of theproducts of the add-on reaction in the presence of 1× HG and4× HG, and with HG without added seeds (No Seeds). The blackarrow points to oligoclusters that are too large to enter the gel.
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fig4: Polyacrylamide gradientgel electrophoresis and TEM images of theproducts of the add-on procedure with different mixtures of seedsand HG. (A) Lane 1, 20 s seeds without HG (no HG); lanes 2–5,the products obtained after add-on reactions with 20 s seeds in thepresence of 1/2×, 1×, 2×, and 4× HG. (B) Lane1, the products of the add-on reaction with HG in the absence of seeds(No Seeds); lanes 2–4, 5–7, and 8–10, the productsobtained with 5, 20, and 30 s seeds after add-on reactions with noHG, 1×, and 2× HG. Note that the overall sizes of the oligoclustersincrease in proportion both to the sizes of the seeds and to the amountof HG. (C) TEM images of 30 s seeds without HG (no HG) and of theproducts of the add-on reaction in the presence of 1× HG and4× HG, and with HG without added seeds (No Seeds). The blackarrow points to oligoclusters that are too large to enter the gel.

Mentions: The gelillustrated in Figure 4A comparesthe products obtained with 1 mM 20 s delay-time seeds and progressivelyincreasing amounts of 1 mM HG. The average size of the oligoclustersincreases as the relative amount of HG increases. The sizes of theoligoclusters are comparable to those obtained using the delay-timeprocedure; and the size distributions are as narrow. The gel in Figure 4B shows that HG can add-on to seeds of differentsizes. Note that, in the presence of NaSCN, HG can still form oligoclusterswithout the addition of seeds, although the clusters are too largeto enter this (4%) acrylamide gel (lane 1, No Seeds).


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)

Polyacrylamide gradientgel electrophoresis and TEM images of theproducts of the add-on procedure with different mixtures of seedsand HG. (A) Lane 1, 20 s seeds without HG (no HG); lanes 2–5,the products obtained after add-on reactions with 20 s seeds in thepresence of 1/2×, 1×, 2×, and 4× HG. (B) Lane1, the products of the add-on reaction with HG in the absence of seeds(No Seeds); lanes 2–4, 5–7, and 8–10, the productsobtained with 5, 20, and 30 s seeds after add-on reactions with noHG, 1×, and 2× HG. Note that the overall sizes of the oligoclustersincrease in proportion both to the sizes of the seeds and to the amountof HG. (C) TEM images of 30 s seeds without HG (no HG) and of theproducts of the add-on reaction in the presence of 1× HG and4× HG, and with HG without added seeds (No Seeds). The blackarrow points to oligoclusters that are too large to enter the gel.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: Polyacrylamide gradientgel electrophoresis and TEM images of theproducts of the add-on procedure with different mixtures of seedsand HG. (A) Lane 1, 20 s seeds without HG (no HG); lanes 2–5,the products obtained after add-on reactions with 20 s seeds in thepresence of 1/2×, 1×, 2×, and 4× HG. (B) Lane1, the products of the add-on reaction with HG in the absence of seeds(No Seeds); lanes 2–4, 5–7, and 8–10, the productsobtained with 5, 20, and 30 s seeds after add-on reactions with noHG, 1×, and 2× HG. Note that the overall sizes of the oligoclustersincrease in proportion both to the sizes of the seeds and to the amountof HG. (C) TEM images of 30 s seeds without HG (no HG) and of theproducts of the add-on reaction in the presence of 1× HG and4× HG, and with HG without added seeds (No Seeds). The blackarrow points to oligoclusters that are too large to enter the gel.
Mentions: The gelillustrated in Figure 4A comparesthe products obtained with 1 mM 20 s delay-time seeds and progressivelyincreasing amounts of 1 mM HG. The average size of the oligoclustersincreases as the relative amount of HG increases. The sizes of theoligoclusters are comparable to those obtained using the delay-timeprocedure; and the size distributions are as narrow. The gel in Figure 4B shows that HG can add-on to seeds of differentsizes. Note that, in the presence of NaSCN, HG can still form oligoclusterswithout the addition of seeds, although the clusters are too largeto enter this (4%) acrylamide gel (lane 1, No Seeds).

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