title: In vivo renal clearance, biodistribution, toxicity of gold nanoclusters.
abstract: 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 h 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 h. 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 h, 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.
authors.affiliation: Institute of Radiation Medicine and Tianjin Key Laboratory of Molecular Nuclear Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300072, China. xiaodongzhang@yahoo.cn
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhang
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Xiu
authors.initials: X
authors.lastname: Shen
authors.forename: Pei-Xun
authors.initials: PX
authors.lastname: Liu
authors.forename: Fei-Yue
authors.initials: FY
authors.lastname: Fan
authors.forename: Sai-Jun
authors.initials: SJ
authors.lastname: Fan
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D006046:Gold / Q000737:chemistry* / Q000378:metabolism*; D006405:Hematology; D007668:Kidney / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000009:adverse effects / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D046529:Microscopy, Electron, Transmission; D011897:Random Allocation
chemical_list: D006046:Gold