The bioaccumulation and toxicity induced by gold nanoparticles in rats <i>in vivo</i> can be detected by ultraviolet-visible (UV-visible) spectroscopy

Abstract

It is essential to characterize the bioaccumulation and toxicity of gold nanoparticles (GNPs) in blood prior to using them in drug delivery, diagnostics, and treatment. The aim of the present study was to evaluate the blood absorbance spectra after intraperitoneal administration of 50 μl of 10, 20, and 50 nm GNPs in rat for periods of 3 and 7 days to assess their bioaccumulation and toxic effects. Healthy, male Wistar-Kyoto rats, 8 to 12 weeks old (approximately 250 g body weight) were used. 40 rats were divided into four groups; a control group and three test groups (each group was composed of 10 rats); control group (NG: n = 10), test group 1 (G1) (A: infusion of 20 nm GNPs for 3 days; n = 5; B: infusion of 20 nm GNPs for 7 days; n = 5), test group 2 (G2) (A: infusion of 10 nm GNPs for 3 days; n = 5; B: infusion of 10 nm GNPs for 7 days; n = 5) and test group 3 (G3) (A: infusion of 50 nm GNPs for 3 days; n = 5; B: infusion of 50 nm GNPs for 7 days; n = 5). Doses consisting of 50 l of 10, 20, and 50 nm GNPs dissolved in aqueous solution were administered to the animals via intraperitoneal administration every day for 3 and 7 days. The blood absorbance spectra were obtained using an ultraviolet-visible (UV-VIS) double beam spectrophotometer. Five peaks were observed for normal blood, characteristic of hemoglobin (Hb) macromolecules. After administration of GNPs, absorbance peaks for G1A and G1B decreased significantly and shifted towards the UV compared with the control. The G1A peak decreased significantly compared to G1B. The G2A and G2B peaks also shifted towards the UV compared with the control. All peaks for G2A increased with no significant changes compared with the control while those for G2B decreased significantly. We observed a marked decrease in absorbance for all G3A and G3B peaks and a shifting towards the UV compared with the control. The absorbance peaks for G3A decreased significantly compared with G3B. This study suggests that the decrease in absorbance observed in G1A, G1B, G2A, G3A, and G3B might be attributed to changes in aliphatic and aromatic amino acids, globin-heme, and heme-heme interaction bands. This study demonstrates that as GNP size increases (for example, a decrease in number of GNPs), the absorbance peaks decreased in intensity and shifted towards the UV. The smaller (10 and 20 nm) GNPs demonstrated a smaller decrease in blood absorbance while the larger (50 nm) GNPs indicated a larger decrease in absorbance spectra relative to control. This study also implies that the blood absorbance spectra are particle size and exposure duration dependent, and that UV-visible spectroscopy may be used as a diagnostic for bioaccumulation and toxicity of GNPs in blood. Our results further suggest that the smaller decrease in blood absorbance spectra might indicate that smaller GNPs are mostly taken up and accumulate in tissues, suggesting toxic effects may be induced by smaller GNPs. These conclusions are further supported by histological observations that suggest toxic effects are induced by smaller GNPs deposited in tissue.

Key words: Gold nanoparticles, size, ultraviolet-visible (UV-visible), blood, rats, spectroscopy, toxicity, histology, liver.