Yang Chengzhi, Tian Aiju, Li Zijian
Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education and Beijing Key Laboratory of Cardiovasicular Receptors Research Beijing 100191, China.
Sci Rep. 2016 Feb 1;6:20203. doi: 10.1038/srep20203.
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.
金纳米颗粒（GNPs）因其在生物医学应用中的巨大潜在价值而受到越来越多的关注。目前，尚未有关于重复给药后GNPs慢性心脏毒性的研究报道。在此，我们对GNPs对心脏的慢性心脏毒性进行了全面评估。将三种不同尺寸（10、30和50纳米）的聚乙二醇（PEG）包被的GNPs或PBS通过尾静脉连续14天注射给小鼠。然后在首次注射后2周、4周或12周对小鼠实施安乐死。分析了GNPs在小鼠心脏中的蓄积情况及其对心脏功能、结构、纤维化和炎症的影响。尺寸较小的GNPs显示出更高的蓄积和更快的清除速度。三种尺寸的GNPs均未影响心脏收缩功能。接受10纳米PEG-GNPs注射2周的小鼠，其左心室内径舒张末期内径（LVIDd）、左心室质量（LVMass）和心脏重量/体重（HW/BW）显著增加，但在4周或12周时未出现这种情况。这些结果表明，小尺寸GNPs的蓄积可诱导可逆性心脏肥大。我们的结果为GNPs在心脏病中的进一步生物医学应用提供了依据。
