Wu Junguang, Ding Jie, Wang Pengyang, Zhang Lili, Lu An-Hui, Zhang Xiang-Qian, Chen Chunying, Wang Liming
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Beijing 100190, China.
Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201204, China.
J Nanosci Nanotechnol. 2020 Apr 1;20(4):2584-2591. doi: 10.1166/jnn.2020.17218.
Magnetic iron oxide (Fe₃O₄) nanoparticles (NPs) have attracted extensive attentions in biomedical fields such as magnetic resonance imaging (MRI). However, the instability and unfavorable dispersity of bare Fe₃O₄ NPs is a challenge for biomedical applications. Herein, we proposed a strategy using hollow carbon sphere (HCS) as a shell structure to endow Fe₃O₄ NPs better stability, dispersity, as well as biocompatibility. To verify intracellular behaviors and biosafety of HCSdecorated Fe₃O₄ nanoparticles (Fe₃O₄@HCS NPs), the assessment of cellular effects of these NPs based on synchrotron radiation-based techniques were done to explore detailed interaction between Fe₃O₄@HCS NPs and liver cells, HepG2. We found that a large number of NPs were internalized by cells in a time-dependent manner determined by inductively coupled plasma mass spectrometry (ICP-MS), which was further supported by intracellular accumulation of iron via X-ray fluorescence (XRF) imaging. Moreover, confocal imaging showed that these NPs mainly located in the lysosomes where they remained stable and undissolved within 72 hours, which was verified by chemical form characterization of iron via Fe K-edge X-ray adsorption near edge structure (XANES). With the coating shell of HCS, the release of iron ions was prevented even in acidic lysosome and the integrity of lysosomal membrane remained unchanged during the storage of NPs. As a result, Fe₃O₄@HCS NPs exhibited low level of oxidative stress and induced negligible cytotoxicity towards HepG2 cells. Based on the powerful techniques, we demonstrated that the carbon outer layer provides a physical barrier that helps remain excellent properties of magnetic Fe₃O₄ NPs and good dispersity, chemical stability, as well as biocompatibility for potential applications in biomedical fields.
磁性氧化铁（Fe₃O₄）纳米颗粒（NPs）在生物医学领域如磁共振成像（MRI）中引起了广泛关注。然而，裸Fe₃O₄ NPs的不稳定性和不良分散性是生物医学应用中的一个挑战。在此，我们提出了一种策略，使用空心碳球（HCS）作为壳结构，赋予Fe₃O₄ NPs更好的稳定性、分散性以及生物相容性。为了验证HCS修饰的Fe₃O₄纳米颗粒（Fe₃O₄@HCS NPs）的细胞内行为和生物安全性，基于同步辐射技术对这些NPs的细胞效应进行了评估，以探索Fe₃O₄@HCS NPs与肝癌细胞HepG2之间的详细相互作用。我们发现，通过电感耦合等离子体质谱（ICP-MS）测定，大量的NPs以时间依赖性方式被细胞内化，这通过X射线荧光（XRF）成像对细胞内铁的积累得到了进一步支持。此外，共聚焦成像显示这些NPs主要位于溶酶体中，在72小时内它们在其中保持稳定且未溶解，这通过Fe K边X射线吸收近边结构（XANES）对铁的化学形态表征得到了验证。有了HCS的包覆壳，即使在酸性溶酶体中也能防止铁离子的释放，并且在NPs储存期间溶酶体膜的完整性保持不变。结果，Fe₃O₄@HCS NPs表现出低水平的氧化应激，对HepG2细胞诱导的细胞毒性可忽略不计。基于这些强大的技术，我们证明了碳外层提供了一个物理屏障，有助于保持磁性Fe₃O₄ NPs的优异性能以及良好的分散性、化学稳定性以及生物相容性，以便在生物医学领域进行潜在应用。
