posted on 2013-06-19, 00:00authored byMegan
A. Mackey, Farhat Saira, Mahmoud A. Mahmoud, Mostafa A. El-Sayed
Recently,
we have shown that targeting the cancer cell nucleus
with solid gold nanospheres, using a cancer cell penetrating/pro-apoptotic
peptide (RGD) and a nuclear localization sequence peptide (NLS), inhibits
cell division, thus leading to apoptosis. In the present work, flow
cytometric analysis revealed an increase in cell death, via apoptosis
and necrosis, in HSC cells upon treatment with peptide-conjugated
hollow gold nanocages, compared to those treated with the peptide-conjugated
solid gold nanospheres. This is consistent with a G0/G1 phase accumulation,
S phase depletion, and G2/M phase depletion, as well as reduced ATP
levels. Here, we investigate the possible causes for the observed
enhanced cell death with the use of confocal microscopy. The fluorescence
images of HSC cells treated with gold nanocages indicate the presence
of reactive oxygen species, known to cause apoptosis. The formation
of reactive oxygen species observed is consistent with a mechanism
involving the oxidation of metallic silver on the inner cavity of
the nanocage (inherent to the synthesis of the gold nanocages) to
silver oxide. This oxidation is confirmed by an observed redshift
in the surface plasmon resonance of the gold nanocages in cell culture
medium. The silver oxide, a semiconductor known to photochemically
generate hydroxyl radicals, a form of reactive oxygen species, is
proposed as a mechanism for the enhanced cell death caused by gold
nanocages. Thus, the enhanced cell death, via apoptosis and necrosis,
observed with peptide-conjugated hollow gold nanocage-treated cells
is considered to be a result of the metallic composition (silver remaining
on the inner cavity) of the nanocage.