Department of Nanobiology, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
Centre for Advanced Material Application, Slovak Academy of Sciences, Bratislava, Slovakia.
Int J Nanomedicine. 2024 May 8;19:4103-4120. doi: 10.2147/IJN.S443168. eCollection 2024.
Gold nanoparticles are promising candidates as vehicles for drug delivery systems and could be developed into effective anticancer treatments. However, concerns about their safety need to be identified, addressed, and satisfactorily answered. Although gold nanoparticles are considered biocompatible and nontoxic, most of the toxicology evidence originates from in vitro studies, which may not reflect the responses in complex living organisms.
We used an animal model to study the long-term effects of 20 nm spherical AuNPs coated with bovine serum albumin. Mice received a 1 mg/kg single intravenous dose of nanoparticles, and the biodistribution and accumulation, as well as the organ changes caused by the nanoparticles, were characterized in the liver, spleen, and kidneys during 120 days.
The amount of nanoparticles in the organs remained high at 120 days compared with day 1, showing a 39% reduction in the liver, a 53% increase in the spleen, and a 150% increase in the kidneys. The biological effects of chronic nanoparticle exposure were associated with early inflammatory and fibrotic responses in the organs and were more pronounced in the kidneys, despite a negligible amount of nanoparticles found in renal tissues.
Our data suggest, that although AuNPs belong to the safest nanomaterial platforms nowadays, due to their slow tissue elimination leading to long-term accumulation in the biological systems, they may induce toxic responses in the vital organs, and so understanding of their long-term biological impact is important to consider their potential therapeutic applications.
金纳米颗粒作为药物传递系统的载体具有很大的应用前景，可开发成有效的抗癌治疗方法。然而，需要明确、解决并令人满意地回答有关其安全性的问题。尽管金纳米颗粒被认为具有生物相容性和低毒性，但大多数毒理学证据都来自于体外研究，这可能无法反映复杂生物体中的反应。
我们使用动物模型来研究 20nm 球形金纳米颗粒（表面覆盖牛血清白蛋白）的长期影响。小鼠接受了 1mg/kg 的单次静脉内纳米颗粒剂量，在 120 天内对肝脏、脾脏和肾脏中纳米颗粒的生物分布和积累以及由纳米颗粒引起的器官变化进行了特征描述。
与第 1 天相比，120 天时器官中的纳米颗粒数量仍然很高，肝脏中的纳米颗粒减少了 39%，脾脏中的纳米颗粒增加了 53%，肾脏中的纳米颗粒增加了 150%。慢性纳米颗粒暴露的生物学效应与器官中的早期炎症和纤维化反应有关，尽管在肾脏组织中发现的纳米颗粒数量微不足道，但在肾脏中更为明显。
我们的数据表明，尽管 AuNPs 属于当今最安全的纳米材料平台，但由于其在生物系统中的缓慢组织消除导致长期积累，它们可能会在重要器官中引起毒性反应，因此了解其长期的生物学影响对于考虑其潜在的治疗应用非常重要。
