Abstract
Gold nanoparticles (GNPs) are attracting more and more attention for their great potential value in biomedical application. Currently, no study has been reported on the chronic cardiac toxicity of GNPs after repeated administration. Here we carried out a comprehensive evaluation of the chronic cardiac toxicity of GNPs to the heart. Polyethylene glycol (PEG) -coated GNPs at three different sizes (10, 30 and 50 nm) or PBS was administrated to mice via tail vein for 14 consecutive days. Then the mice were euthanized at 2 weeks, 4 weeks or 12 weeks after the first injection. The accumulation of GNPs in the mouse heart and their effects on cardiac function, structure, fibrosis and inflammation were analysized. GNPs with smaller size showed higher accumulation and faster elimination. None of the three sizes of GNPs affected cardiac systolic function. The LVIDd (left ventricular end-diastolicinner-dimension), LVMass (left ventricular mass) and HW/BW (heart weight/body weight) were significantly increased in the mice receiving 10 nm PEG-GNPs for 2 weeks, but not for 4 weeks or 12 weeks. These results indicated that the accumulation of small size GNPs can induce reversible cardiac hypertrophy. Our results provide the basis for the further biomedical applications of GNPs in cardiac diseases.
Highlights
This study was to address the biological accumulation and safety of chronic gold nanoparticles (GNPs) exposure in the heart
These results showed that chronic GNPs exposure did not induce inflammatory cells infiltration in the mouse heart, whereas 50 nm GNPs led to a significant decrease in the TNF-α and IL-1β level in the heart of mice
We found that 10 nm polyethylene glycol (PEG)-GNPs can cause reversible cardiac hypertrophy at the 2th week after repeated administration in mice
Summary
The result showed that accumulation of GNPs in the heart was in a size-dependent manner at three time point (Fig. 2). These results indicated that the GNPs accumulated in the mouse heart did not affect cardiac systolic function. Consistent with the HW/BW, there was a significant increase in LVMass in the mice that received 10 nm GNPs for 2 weeks compared with the vehicle group (91.89 ± 2.01 mg vs 83.41 ± 2.64 mg, P < 0.05, Fig. 4E).
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