  Gold nanoparticles have shown great prospective in cancer diagnosis and
therapy, but they can not be metabolized and prefer to accumulate in liver and
spleen due to their large size. The gold nanoclusters with small size can
penetrate kidney tissue and have promise to decrease in vivo toxicity by renal
clearance. In this work, we explore the in vivo renal clearance,
biodistribution, and toxicity responses of the BSA- and GSH-protected gold
nanoclusters for 24 hours and 28 days. The BSA-protected gold nanoclusters have
low-efficient renal clearance and only 1% of gold can be cleared, but the
GSH-protected gold nanoclusters have high-efficient renal clearance and 36 % of
gold can be cleared after 24 hours. The biodistribution further reveals that
94% of gold can be metabolized for the GSH-protected nanoclusters, but only
less than 5% of gold can be metabolized for the BSA-protected nanoclusters
after 28 days. Both of the GSH- and BSA-protected gold nanoclusters cause acute
infection, inflammation, and kidney function damage after 24 hours, but these
toxicity responses for the GSH-protected gold nanoclusters can be eliminated
after 28 days. Immune system can also be affected by the two kinds of gold
nanoclusters, but the immune response for the GSH-protected gold nanoclusters
can also be recovered after 28 days. These findings show that the GSH-protected
gold nanoclusters have small size and can be metabolized by renal clearance and
thus the toxicity can be significantly decreased. The BSA- protected gold
nanoclusters, however, can form large compounds and further accumulate in liver
and spleen which can cause irreparable toxicity response. Therefore, the
GSH-protected gold nanoclusters have great potential for in vivo imaging and
therapy, and the BSA-protected gold nanoclusters can be used as the agent of
liver cancer therapy.
