Size-dependent in vivo toxicity of PEG-coated gold nanoparticles

Abstract

Background: Gold nanoparticle toxicity research is currently leading towards the in vivo experiment. Most toxicology data show that the surface chemistry and physical dimensions of gold nanoparticles play an important role in toxicity. Here, we present the in vivo toxicity of 5, 10, 30, and 60 nm PEG-coated gold nanoparticles in mice.

Methods: Animal survival, weight, hematology, morphology, organ index, and biochemistry were characterized at a concentration of 4000 μg/kg over 28 days.

Results: The PEG-coated gold particles did not cause an obvious decrease in body weight or appreciable toxicity even after their breakdown in vivo. Biodistribution results show that 5 nm and 10 nm particles accumulated in the liver and that 30 nm particles accumulated in the spleen, while the 60 nm particles did not accumulate to an appreciable extent in either organ. Transmission electron microscopic observations showed that the 5, 10, 30, and 60 nm particles located in the blood and bone marrow cells, and that the 5 and 60 nm particles aggregated preferentially in the blood cells. The increase in spleen index and thymus index shows that the immune system can be affected by these small nanoparticles. The 10 nm gold particles induced an increase in white blood cells, while the 5 nm and 30 nm particles induced a decrease in white blood cells and red blood cells. The biochemistry results show that the 10 nm and 60 nm PEG-coated gold nanoparticles caused a significant increase in alanine transaminase and aspartate transaminase levels, indicating slight damage to the liver.

Conclusion: The toxicity of PEG-coated gold particles is complex, and it cannot be concluded that the smaller particles have greater toxicity. The toxicity of the 10 nm and 60 nm particles was obviously higher than that of the 5 nm and 30 nm particles. The metabolism of these particles and protection of the liver will be more important issues for medical applications of gold-based nanomaterials in future.

Keywords: gold nanoparticles; in vivo; size; toxicity.

Figure 1

Transmission electron micrographs and optical absorption of 5, 10, 30, and 60 nm PEG-coated gold particles.

Figure 2

Body weight changes in mice for the 5, 10, 30, and 60 nm PEG-coated gold particles at a dose of 4000 μg/kg. The body weight of the treated mice was measured every 2 days. Each point represents the mean ± standard deviation of six mice. Data were analyzed using the Student’s t-test and the differences between the different doses and control group for each organ were not significant (P > 0.05).

Figure 3

Biodistribution of body weight in mice for 5, 10, 30, and 60 nm PEG-coated gold particles at the dose of 4000 μg/kg after 28 days of treatment. Spleen and liver were the main target accumulation organs. The 5 nm particles had a wide distribution in live, heart, kidney, while the 10 and 30 nm particles preferentially stayed in the liver and spleen, respectively.

Figure 4

Transmission electron micrographs of 5, 10, 30, and 60 nm PEG-coated gold particles in bone marrow and blood cells 28 days after intraperitoneal injection at a dose of 4000 μg/kg. In the bone marrow cells, the gold particles can be found as monodispersed particles, and aggregations of 10 nm and 60 nm particles are found in the blood cells.

Figure 5

Size-dependent spleen and thymus indices of mice were calculated 28 days after 4000 μg/kg intraperitoneal injections. Notes: All values are reported as the mean ± standard deviation. Data were analyzed using Student’s t-test. *Represents a significant difference from the control group (P < 0.05).

Figure 6

Size-dependent hematology results from mice treated with PEG-coated gold nanoparticles and control group 28 days after intraperitoneal injection at the dose of 4000 μg/kg. These results show mean and standard deviations of (A) white blood cells, (B) red blood cell, (C) hemoglobin, (D) mean corpuscular hemoglobin, (E) platelet, (F) hematocrit, (G) mean corpuscular volume, and (H) mean corpuscular hemoglobin concentration. Notes: Bars represent mean ± standard deviation. Data were analyzed using the Student’s t-test. *Represents a significant difference from the control group (P < 0.05). Abbreviations: WBC, white blood cells; RBC, red blood cell; HGB, hemoglobin; MCH, mean corpuscular hemoglobin; PLT, platelet; HCT, hematocrit; MCV, mean corpuscular volume; MCHC, mean corpuscular hemoglobin concentration.

Figure 7

Size-dependent biochemical results for mice treated with PEG-coated gold nanoparticles and control group 28 days after intraperitoneal injection at a dose of 4000 μg/kg. These results show mean and standard deviations of (A) alanine transaminase, (B) aspartate transaminase, (C) blood urea nitrogen, (D) globulin, (E) creatinine, (F) total protein, (G) albumin, and (H) total bilirubin. Notes: Bars represent mean ± standard deviation. Data were analyzed by Student’s t-test. *Represents significant difference from the control group (P < 0.05). Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; BUN, blood urea nitrogen, GLOB, globulin, CREA creatinine; TP, total protein; ALB, albumin; TBIL, total bilirubin.