Can the gold ion to cross biological membranes?

[Prof.Nikolai]

I would like your opinion on a biological issue.

I am analyzing the toxicity of gold nanoparticles (AuNPs) and I'm almost sure that the mechanism of toxicity of these nanoparticles is due to multiple effects very different from the effects observed by other types of nanoparticles (silver, titanium oxide, etc.).

Indeed all other types of nanoparticles can release ions while AuNPs can not ionize. To definitively demonstrate this effect I want to understand whether the metal ions can cross biological membranes. In addition, I would like to understand whether gold ions can enter and/or exit from the different cellular vesicles.

Thank you very much for your help,

Nikolai

[John Cuthber]

There area gold based drugs that contain (complexed) gold ions

If those didn't pass through cell membranes then they wouldn't work (unless the site of action was the cell membrane itself).

http://en.wikipedia.org/wiki/Gold_salts#Medical_uses

[dmaiski]

There area gold based drugs that contain (complexed) gold ions

If those didn't pass through cell membranes then they wouldn't work (unless the site of action was the cell membrane itself).

http://en.wikipedia....ts#Medical_uses

i searched for the toxicity of gold and this is what came up

http://www.ncbi.nlm....les/PMC2988217/

 

that paper is scary... is uses "could"(9 times) instead of "do"(0 times)

the only place where "do" is used is in the reference:

 

 

"Connor EE, Mwamuka J, Gole A, Murphy CJ, Wyatt MD. Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small. 2005;1:325–327. doi: 10.1002/smll.200400093. [PubMed] [Cross Ref]"

Edited September 28, 2012 by dmaiski

[John Cuthber]

Then find a better paper.

Even this

http://en.wikipedia.org/wiki/Gold#Toxicity

is probably an improvement.

[dmaiski]

www.nanoarchive.org/6517/1/024A56CBd01.pdf

 

may be relevant

 

short summary: in sufficiently high doses gold NP are lethal to mice models as long as gold NP are between 8-37 nm diameter, smaller and larger particles had no effect

 

 

 

 

[CharonY]

I think the question is aimed at something different. In most tox studies significant aggregation of NP is happening resulting in various forms of cell entry (including endocytosis). However, most metal NP appear to create oxidative stress (with a few studies suggesting alternative, but mostly uncharacterized pathways).

Metal ions do permeate membrane (via porins and certain ion channels, mostly), however the concentration of free metals tend to be relatively low in solution. I am not aware (but certainly am not an authority in this area) of any differences in this regard between gold and other metals.

 

I am a bit wary with regards to tox data on NP as at least the initial ones did not control well for further aggregation (as mentioned), in one case rats were killed with carbon nanotubes, but not due to toxicity, but because they were literally suffocated. The various groups are improving their assays, but I have not yet seen anything terribly conclusive in terms of mechanisms. So far the convention wisdom tends to be that it is a matter of available surface rather than any new mechanism (nano compared to bulk, that is). There are exceptions that suggest otherwise, but good data is hard to find and good explanation even harder.

Edited September 28, 2012 by CharonY

[Prof.Nikolai]

I have observed the presence of Gold NPs in cells by TEM analysis. The nanoparticles enter into the cells, but many are located on the outside of the cells membrane. Analysis by confocal microscopy (scattering 633nm) show the presence of nanoparticles around the nucleus but the same cells analyzed by TEM do not present NPs around the nucleus. The increased number of particles scattering around the nucleus of cells treated with Gold NPs is due to some biological effect, probably they are microvesicles. By ICP-MS analysis of cells treated with Gold NPs is impossible to understand if the amount of gold detected derives from NPs adhering to the cell membrane (external side) or not. Furthermore, it is difficult to assess the presence of gold ions in the solutions, in fact analyzing solutions after centrifugation or filtration by TEM can be observed NPs. Centrifugation and filtration are not able to completely eliminate the NPs from a solution. Finally, gold is unaffected by air, moisture and most corrosive reagents, and is therefore well suited for use in coins and jewelry and as a protective coating on other, more reactive, metals. However, it is not chemically inert. Gold is almost insoluble, but can be dissolved in aqua regia.

Common oxidation states of gold include +1 (gold(I) or aurous compounds) and +3 (gold(III) or auric compounds). Gold ions in solution are readily reduced and precipitated out as gold metal by adding any other metal as the reducing agent. The added metal is oxidized and dissolves allowing the gold to be displaced from solution and be recovered as a solid precipitate. Gold first ionization energy 1st: 890.1 kJ·mol⁻¹