Size-dependent tissue kinetics of PEG-coated gold nanoparticles.
Gold nanoparticles (AuNPs) can be used in various biomedical applications, however, very little is known about their size-dependent in vivo kinetics. Here, we performed a kinetic study in mice with different sizes of PEG-coated AuNPs. Small AuNPs (4 or 13nm) showed high levels in blood for 24h and were cleared by 7days, whereas large (100nm) AuNPs were completely cleared by 24h. All AuNPs in blood re-increased at 3months, which correlated with organ levels. Levels of small AuNPs were peaked at 7days in the liver and spleen and at 1month in the mesenteric lymph node, and remained high until 6months, with slow elimination. In contrast, large AuNPs were taken up rapidly ( approximately 30min) into the liver, spleen, and mesenteric lymph nodes with less elimination phase. TEM showed that AuNPs were entrapped in cytoplasmic vesicles and lysosomes of Kupffer cells and macrophages of spleen and mesenteric lymph node. Small AuNPs transiently activated CYP1A1 and 2B, phase I metabolic enzymes, in liver tissues from 24h to 7days, which mirrored with elevated gold levels in the liver. Large AuNPs did not affect the metabolic enzymes. Thus, propensity to accumulate in the reticuloendothelial organs and activation of phase I metabolic enzymes, suggest that extensive further studies are needed for practical in vivo applications.
Cho
Wan-Seob
WS
The University of Edinburgh, Edinburgh, EH16 4TJ, UK.
Cho
Minjung
M
Jeong
Jinyoung
J
Choi
Mina
M
Han
Beom Seok
BS
Shin
Hyung-Seon
HS
Hong
Jin
J
Chung
Bong Hyun
BH
Jeong
Jayoung
J
Cho
Myung-Haing
MH
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D006046:Gold / Q000493:pharmacokinetics* / Q000652:urine; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D050216:Metabolic Detoxication, Phase I; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D013154:Spleen / Q000378:metabolism
D011092:Polyethylene Glycols; D006046:Gold; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1