Size- and Ligand-Specific Bioresponse of Gold Clusters and Nanoparticles: Challenges and Perspectives - Gold Clusters, Colloids and Nanoparticles - page 205

reduced, since the equilibrium of dissociation is shifted. However, GSH, NAC, and
phosphines can also be considered as antioxidants. In order to exclude reducing
properties of these compounds as reason for the restricted cytotoxicity, ascorbic
acid as a strong reducer was tested. As could be expected, the cytotoxicity of
Au 55 (Ph 2 PC 6 H 4 SO 3 Na) 12 Cl 6 was unchanged compared with experiments without
ascorbic acid [ 22 ].These experiments clearly indicate the repeatedly mentioned
condition that bare Au 55 surfaces are necessary for the interaction with vital
biological targets to observe cytotoxicity.
This finding is further corroborated by studies on the interaction of 1.4 nm Au
clusters with ion channels [ 87 ]. The human ether-`-go-go-related potassium channel
(hERG) is intensely studied and is known to interact withmultiplemolecular ligands.
By patch clamp technique in hERG channel-transfected HEK293 cells, it was shown
that 1.4 nm phosphine-stabilized AuNP irreversibly blocked hERG channels,
whereas thiol-stabilized AuNP of similar size had no effect.
4 Properties In Vivo
4.1 Biodistribution
The toxicity phenomena discussed before have all been observed in cell cultures,
i.e., in vitro. However, from experience we know that toxicity problems in a living
being can be characteristically different depending on the kind of administration
and distribution in the body. Radiolabeling by 198 Au isotopes allows very precise
determination of the distribution in the different organs, though very low
concentrations have to be used in order to avoid toxicity effects. In a series of
experiments with 1.4, 5, 18, 80, and 200 nm AuNPs, all protected with the proven
phosphine ligand Ph 2 PC 6 H 4 SO 3 Na, the influence of size on the biodistribution
in healthy female Wistar-Kyoto rats in the course of 24 h has been studied
[ 88 - 90 ]. ʳ -Spectroscopy has been applied to determine the gold content in the
various organs. The administration was performed by intravenous injection
(i.v., tail vein). As can be followed from Fig. 15 , the 5, 18, 80, and 200 nm
AuNPs are accumulated with 92-97% in the liver, in contrast to the 1.4 nm species
which accumulates only with ca. 50% in this organ.
A detailed comparison of the biodistribution of 1.4 and 18 nm AuNPs is given in
Fig. 16 . A more or less quantitative accumulation of the 18 nm species in the liver
can be registered, whereas 50% of the 1.4 nm clusters are distributed over the lung,
spleen, kidney, blood, and urine [ 89 , 90 ].
Considering the findings that traces of the 1.4 nm Au 55 cluster could be found in
the heart, brain, and uterus (not shown in Fig. 16 ), it clearly turns out that
biodistribution of this species dominates, compared with larger AuNPs. Regarding
its cell toxicity, Au 55 particles must be considered as very dangerous if present in
the blood stream.