Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran.
Research Center of Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Int J Nanomedicine. 2018 Mar 13;13:1483-1493. doi: 10.2147/IJN.S157293. eCollection 2018.
The possibility of using a specific nanoparticle in nanomedicine highly depends on its biodistribution profile and biocompatibility. Due to growing demand for iron oxide nanoparticles (IONPs) and dendrimers in biomedical applications, this study was performed to assess the biodistribution, pharmacokinetics, and toxicity of dendrimer-coated iron oxide nanoparticles (G@IONPs).
IONPs were synthesized via co-precipitation and coated with the fourth generation (G) of polyamidoamine (PAMAM) dendrimer. To determine the biodistribution, 5 mg/mL G@IONPs suspension was intraperitoneally injected into tumor-bearing BALB/c mice, and iron levels in blood and various organs, including the lung, liver, brain, heart, tumor, and kidney, were measured by inductively coupled plasma mass spectrometry (ICP-MS) at 4, 8, 12, and 24 h after injection. Also, to investigate the toxicity of G@IONPs, different concentrations of G@IONPs were injected into BALB/c mice, and blood, renal, and hepatic factors were measured. Furthermore, histopathological staining was performed to investigate the effect of G@IONPs on the liver and kidney tissues.
The results showed that the iron content was higher in the kidney, liver, and lung tissues 24 h after injection. Toxicity assessments revealed a significant increase in blood urea nitrogen (BUN) and direct bilirubin at the concentration of 10 mg/kg. Also, in this concentration, histopathological abnormalities were detected in liver tissue.
Although more systematic studies are still required, our results encouraged the future investigations of G@IONPs in biomedical applications.
特定纳米粒子在纳米医学中的应用可能性高度取决于其生物分布特征和生物相容性。由于氧化铁纳米粒子(IONPs)和树枝状大分子在生物医学应用中的需求不断增长,因此进行了这项研究,以评估树枝状大分子包覆的氧化铁纳米粒子(G@IONPs)的生物分布、药代动力学和毒性。
通过共沉淀法合成 IONPs,并涂覆第四代(G)聚酰胺胺(PAMAM)树枝状大分子。为了确定生物分布,将 5mg/mL G@IONPs 混悬液经腹腔注射到荷瘤 BALB/c 小鼠体内,在注射后 4、8、12 和 24 小时,通过电感耦合等离子体质谱法(ICP-MS)测量血液和包括肺、肝、脑、心、肿瘤和肾在内的各种器官中的铁含量。此外,为了研究 G@IONPs 的毒性,将不同浓度的 G@IONPs 注射到 BALB/c 小鼠体内,测量血液、肾和肝因子。此外,进行了组织病理学染色,以研究 G@IONPs 对肝和肾组织的影响。
结果表明,注射后 24 小时,肾脏、肝脏和肺组织中的铁含量较高。毒性评估显示,在 10mg/kg 浓度下,血液尿素氮(BUN)和直接胆红素显著增加。此外,在该浓度下,肝组织中检测到组织病理学异常。
尽管还需要更多的系统性研究,但我们的结果鼓励未来在生物医学应用中对 G@IONPs 进行研究。