Core–shell structured Fe₃O₄@SiO₂-NH₂ nanoparticles (Fe@Si-NPs) demonstrated outstanding potentials in drug targeting and delivery and medical imaging. However, they have limited clinical applications due to unknown chronic bio-effects and potential bio-related risks. In this study, the subchronic biological effects and metabolic fate of 20 nm Fe@Si-NPs in Sprague–Dawley rats in 12 weeks were investigated by the biochemical assay and NMR-based metabonomic analysis using an intravenous model. Biofluids (plasma and urine) analysis provided the transportation, absorption, and excretion information of Fe@Si-NPs. Urine metabonome displayed a metabolic recovery while self-regulation of plasma metabonome leaded to the parallel metabolic trends between dosed and control groups in 12 weeks. And biological tissues (spleen, liver, kidney, and lung) analysis indicated liver and spleen are the targeted-organs of Fe@Si-NPs. The obvious metabolic variations responding to the biodistribution were induced by Fe@Si-NPs although no visible toxic effects were observed in these tissues. Besides the common energy metabolism response to the xenobiotics, Fe@Si-NPs also disturbed the metabolic pathways in glycerophospholipid and sphingolipid metabolism, metabolisms of purine, pyrimidine, and nicotinate. Our results provide preliminary validation for the potential use of Fe@Si-NPs in clinical medicine and give identifiable ground for the dose selection and bio-nanoagent optimization.

中文翻译：

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核壳结构的Fe ₃ O ₄ @SiO ₂ -NH ₂纳米颗粒的代谢命运和亚历时生物学效应

核壳结构的Fe ₃ O ₄ @SiO ₂ -NH ₂纳米粒子（Fe @ Si-NPs）在药物靶向，递送和医学成像方面显示出巨大潜力。但是，由于未知的慢性生物效应和潜在的生物相关风险，它们在临床上的应用受到限制。在这项研究中，通过生化测定和基于NMR的基于NMR的代谢组学分析，研究了12周内Sprague–Dawley大鼠中20 nm Fe @ Si-NPs的亚慢性生物学效应和代谢命运。生物流体（血浆和尿液）分析提供了Fe @ Si-NPs的运输，吸收和排泄信息。尿代谢组显示代谢恢复，而血浆代谢组的自我调节导致剂量组和对照组在12周内出现平行的代谢趋势。和生物组织（脾脏，肝脏，肾脏，和肺）分析表明，肝和脾是Fe @ Si-NPs的靶向器官。Fe @ Si-NPs诱导了明显的响应生物分布的代谢变化，尽管在这些组织中未观察到明显的毒性作用。Fe @ Si-NPs除了对异种生物的常见能量代谢反应外，还干扰了甘油磷脂和鞘脂代谢，嘌呤，嘧啶和烟酸酯的代谢途径。我们的结果为Fe @ Si-NPs在临床医学中的潜在用途提供了初步验证，并为剂量选择和生物纳米剂优化提供了可识别的依据。Fe @ Si-NPs除了对异种生物的常见能量代谢反应外，还干扰了甘油磷脂和鞘脂代谢，嘌呤，嘧啶和烟酸酯的代谢途径。我们的结果为Fe @ Si-NPs在临床医学中的潜在用途提供了初步验证，并为剂量选择和生物纳米剂优化提供了可识别的依据。Fe @ Si-NPs除了对异种生物的常见能量代谢反应外，还干扰了甘油磷脂和鞘脂代谢，嘌呤，嘧啶和烟酸酯的代谢途径。我们的结果为Fe @ Si-NPs在临床医学中的潜在用途提供了初步验证，并为剂量选择和生物纳米剂优化提供了可识别的依据。