Abstract

Iron-oxide nanoparticles are one of the most commercialized nanomaterials and have gained widespread acceptance in nanotherapeutics due to their ability for targeted drug delivery, bioimaging, and various other preclinical and clinical theranostic biomedical applications. However, the absence of regulations, guidelines, and harmonized standards as well as limitations associated with their use in clinical settings in the context of their safety and toxicity profiling necessitates in-depth understanding of their toxicological paradigms. Here we examine the toxicity of modified superparamagnetic iron oxide nanoparticles in Swiss albino mice in terms of body weight changes, organ coefficients, generalized and organ-specific biochemical, and various histological staining parameters after administration of bare (uncoated) magnetic nanoparticles (MNPs) and triple polymer-coated magnetic nanoparticles (MNP-AC-G2-pPEG). Both types of nanoparticles were administered intravenously, in three doses (5, 10, and 25 mg/kg body weight) and results of biochemical and histopathological assessment revealed that the highest dose of bare (uncoated) MNPs significantly altered biochemical and histoarchitectural aspects in vital organs, while coated NPs (MNP-AC-G2-pPEG) was found safe in almost all doses. Furthermore, results of toluidine blue (for mast cells) and Prussian blue (for iron deposition) staining also established that the highest dose administration of bare MNPs in animals significantly enhanced mast cell infiltration and iron deposition in tissue sections of most vital organs, while coated NPs did not demonstrate any such adverse effects. Overall, outcomes of this study aid in establishing that administration of uncoated (bare) magnetic NPs in vivo results in structural and functional toxicological modifications while the coating of these NPs with biocompatible and biodegradable polymers can significantly bring down the toxicity of these NPs.

摘要

氧化铁纳米粒子是最商业化的纳米材料之一，由于其靶向药物递送，生物成像以及各种其他临床前和临床治疗学生物医学应用的能力，已在纳米治疗学中得到广泛接受。但是，由于缺乏法规，指南和统一标准，以及在安全性和毒性分析方面与在临床环境中使用相关的限制，因此需要深入了解其毒理学范式。在这里，我们从体重变化，器官系数，全身性和器官特异性生化方面研究了改性的超顺磁性氧化铁纳米颗粒对瑞士白化病小鼠的毒性，和裸露（未涂层）磁性纳米颗粒（MNP）和三重聚合物涂层磁性纳米颗粒（MNP-AC-G2-pPEG）给药后的各种组织学染色参数。两种类型的纳米颗粒均以三种剂量（5、10和25 mg / kg体重）静脉内给药，生化和组织病理学评估的结果表明，裸露（未包被）MNP的最高剂量显着改变了生命中重要的生化和组织结构器官，而发现包被的NP（MNP-AC-G2-pPEG）在几乎所有剂量下都是安全的。此外，甲苯胺蓝（用于肥大细胞）和普鲁士蓝（用于铁沉积）染色的结果还证实，在动物体内以最高剂量施用裸露的MNP可以显着增强大多数重要器官组织部分的肥大细胞浸润和铁沉积，包被的NPs没有表现出任何这种不利影响。总体而言，这项研究的结果有助于确定未涂覆（裸露）磁性NP的管理体内毒性导致结构和功能上的毒理学修饰，而用生物相容性和可生物降解的聚合物包被这些NP可以大大降低这些NP的毒性。