Engineered Nanomaterials (NMs), such as Superparamagnetic Iron Oxide Nanoparticles (SPIONs), offer significant benefits in a wide range of applications, including cancer diagnostic and therapeutic strategies. However, the use of NMs in biomedicine raises safety concerns due to lack of knowledge on possible biological interactions and effects. The initial basis for using SPIONs as biomedical MRI contrast enhancement agents was the idea that they are selectively taken up by macrophage cells, and not by the surrounding cancer cells. To investigate this claim, we analyzed the uptake of SPIONs into well-established cancer cell models and benchmarked this against a common macrophage cell model. In combination with fluorescent labeling of compartments and siRNA silencing of various proteins involved in common endocytic pathways, the mechanisms of internalization of SPIONs in these cell types has been ascertained utilizing reflectance confocal microscopy. Caveolar mediated endocytosis and macropinocytosis are both implicated in SPION uptake into cancer cells, whereas in macrophage cells, a clathrin-dependant route appears to predominate. Colocalization studies confirmed the eventual fate of SPIONs as accumulation in the degradative lysosomes. Dissolution of the SPIONs within the lysosomal environment has also been determined, allowing a fuller understanding of the cellular interactions, uptake, trafficking and effects of SPIONs within a variety of cancer cells and macrophages. Overall, the behavior of SPIONS in non-phagocytotic cell lines is broadly similar to that in the specialist macrophage cells, although some differences in the uptake patterns are apparent.

中文翻译：

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纳米级临床MRI造影剂的细胞摄取机制。

工程纳米材料（NMs），例如超顺磁性氧化铁纳米颗粒（SPIONs），在包括癌症诊断和治疗策略在内的广泛应用中具有显着优势。然而，由于缺乏对可能的生物相互作用和作用的认识，在生物医学中使用NM引起了安全问题。使用SPIONs作为生物医学MRI对比增强剂的最初基础是这样的想法，即它们被巨噬细胞而不是周围的癌细胞选择性地吸收。为了调查这一说法，我们分析了SPIONs在完善的癌细胞模型中的摄取情况，并针对常见的巨噬细胞模型进行了基准测试。结合区室的荧光标记和参与常见内吞途径的各种蛋白质的siRNA沉默，利用反射共聚焦显微镜已经确定了SPIONs在这些细胞类型中的内在化机理。海绵体介导的内吞作用和巨胞饮作用均与SPION摄入癌细胞有关，而在巨噬细胞中，网格蛋白依赖性途径似乎占主导地位。共定位研究证实了SPIONs最终的命运是在降解的溶酶体中积累。还已经确定了SPION在溶酶体环境中的溶解，从而可以更全面地了解SPION在各种癌细胞和巨噬细胞中的相互作用，摄取，运输和作用。总体而言，SPIONS在非吞噬细胞系中的行为与专业巨噬细胞中的行为大致相似，尽管在摄取方式上存在明显差异。