Laboratoire Matières et Systèmes Complexes, UMR 7057, and Laboratoire Matériaux et Phénomènes Quantiques, UMR 7162, CNRS/Université Paris Diderot, 10 rue Alice Domon et Léonie Duquet, F-75205 Paris Cedex 13, France.
ACS Nano. 2013 May 28;7(5):3939-52. doi: 10.1021/nn305719y. Epub 2013 May 7.
The long-term fate of nanomaterials in biological environment represents a critical matter, which determines environmental effects and potential risks for human health. Predicting these risks requires understanding of nanoparticle transformations, persistence, and degradation, some issues somehow ignored so far. Safe by design, inorganic nanostructures are being envisioned for therapy, yet fundamental principles of their processing in biological systems, change in physical properties, and in situ degradability have not been thoroughly assessed. Here we report the longitudinal visualization of iron oxide nanocube transformations inflicted by the intracellular-like environment. Structural degradation of individual nanocubes with two different surface coatings (amphiphilic polymer shell and polyethylene glycol ligand molecules) was monitored at the atomic scale with aberration-corrected high-resolution transmission electron microscopy. Our results suggest that the polymer coating controls surface reactivity and that availability and access of chelating agents to the crystal surface govern the degradation rate. This in situ study of single nanocube degradation was compared to intracellular transformations observed in mice over 14 days after intravenous injection, revealing the role of nanoparticle clustering, intracellular sorting within degradation compartments, and iron transfer and recycling into ferritin storage proteins. Our approach reduces the gap between in situ nanoscale observations in mimicking biological environments and in vivo real tracking of nanoparticle fate.
纳米材料在生物环境中的长期命运是一个关键问题，它决定了对环境的影响和对人类健康的潜在风险。预测这些风险需要了解纳米颗粒的转化、持久性和降解，而这些问题迄今为止在某种程度上被忽视了。人们设想使用设计安全的无机纳米结构进行治疗，但它们在生物系统中的处理、物理性质的变化和原位降解性等基本原理尚未得到彻底评估。在这里，我们报告了通过类似于细胞内的环境对氧化铁纳米立方体转化进行的纵向可视化。我们使用具有像差校正的高分辨率透射电子显微镜在原子尺度上监测了两种不同表面涂层（两亲聚合物壳和聚乙二醇配体分子）的单个纳米立方体的结构降解。我们的结果表明，聚合物涂层控制着表面反应性，而螯合剂对晶体表面的可用性和可及性决定了降解速率。将这种对单个纳米立方体降解的原位研究与静脉注射后 14 天在小鼠中观察到的细胞内转化进行了比较，揭示了纳米颗粒聚集、降解隔间内的细胞内分类以及铁向铁蛋白储存蛋白的转移和再循环的作用。我们的方法缩小了模拟生物环境中的原位纳米尺度观察与体内真实追踪纳米颗粒命运之间的差距。
