Cetuximab-conjugated gold nanoparticles are known to target cancer cells, but display toxicity towards normal kidney, liver and endothelial cells in vitro. In this study, we investigated their pharmacokinetics, biodistribution and toxicity after intravenous administration in healthy mice. Our data showed that these nanoparticles were rapidly cleared from the blood and accumulated mainly in the liver and spleen with long-term retention. Acute liver injury, inflammatory activity and vascular damage were transient and negligible, as confirmed by the liver functionality tests and serum marker analysis. There was no sign of altered liver, kidney, lung and spleen morphology up to 4 weeks post-injection. After 6 months, kidney casts and splenic apoptosis appeared to be more prevalent than in the controls. Furthermore, occasional immune cell infiltration was observed in the lungs. Therefore, we recommend additional in vivo studies, in order to investigate the long-term toxicity and elimination of gold nanoparticles after multiple dosing in their preclinical validation as new targeted anti-cancer therapies.

中文翻译：

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在体内小鼠体内结合抗体的金纳米粒子的体内药代动力学，生物分布和毒性。

已知西妥昔单抗偶联的金纳米颗粒靶向癌细胞，但在体外对正常的肾脏，肝脏和内皮细胞显示毒性。在这项研究中，我们调查了在健康小鼠中静脉给药后它们的药代动力学，生物分布和毒性。我们的数据表明，这些纳米颗粒可从血液中迅速清除，并主要长期保留在肝脏和脾脏中。肝功能测试和血清标志物分析证实，急性肝损伤，炎性活动和血管损伤是短暂且可忽略的。注射后4周内，没有肝，肾，肺和脾形态改变的迹象。6个月后，肾结石和脾细胞凋亡似乎比对照组更普遍。此外，在肺中偶尔观察到免疫细胞浸润。因此，我们建议其他体内 为了研究金纳米颗粒在临床前验证中作为新的靶向抗癌疗法多次给药后的长期毒性和消除，进行了研究。