Direct quantification of rare earth doped titania nanoparticles in individual human cells.
Direct quantification of rare earth doped titania nanoparticles in individual human cells.
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DOI：
10.1088/0957-4484/27/28/285103
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发表时间：
2016-07-15
期刊：
影响因子：
3.5
通讯作者：
Townley HE
中科院分区：
文献类型：
--
作者：
Jeynes JC;Jeynes C;Palitsin V;Townley HE
掺杂稀土元素的二氧化钛纳米粒子（NPs）有许多可能的生物医学应用，从放射治疗中的剂量增强和诊断成像到生物传感。然而，人们担心纳米颗粒可能在体内分解，从而将有毒的稀土离子释放到不希望的位置。作为第一步，我们研究如何准确地从纳米粒子的Ti/REE比可以在人体细胞内测量。使用质子微探针元素显微镜对完整的、未切片的、单个的人类细胞进行定量分析。该方法的独特之处在于能够以微米分辨率定量分析未切片的单个细胞中的所有元素，同时还可以扫描大视场。我们将细胞内的Ti/REE信号与细胞外的NP进行了比较，NP非特异性地吸收到聚丙烯基底上。我们发现，在单个细胞的REE信号与钛信号共定位，表明NP保持完整。在测量的不确定度范围内，细胞内外的Ti/REE比值没有差异。有趣的是，我们还表明，从细胞到细胞的纳米颗粒的吸收有相当大的变化，超过10倍。我们的结论是，纳米粒子进入细胞，并保持完整。如果要将NP用于治疗，则应考虑细胞间NP浓度的巨大异质性。
There are many possible biomedical applications for titania nanoparticles (NPs) doped with rare earth elements (REEs), from dose enhancement and diagnostic imaging in radiotherapy, to biosensing. However, there are concerns that the NPs could disintegrate in the body thus releasing toxic REE ions to undesired locations. As a first step, we investigate how accurately the Ti/REE ratio from the NPs can be measured inside human cells. A quantitative analysis of whole, unsectioned, individual human cells was performed using proton microprobe elemental microscopy. This method is unique in being able to quantitatively analyse all the elements in an unsectioned individual cell with micron resolution, while also scanning large fields of view. We compared the Ti/REE signal inside cells to NPs that were outside the cells, non-specifically absorbed onto the polypropylene substrate. We show that the REE signal in individual cells co-localises with the titanium signal, indicating that the NPs have remained intact. Within the uncertainty of the measurement, there is no difference between the Ti/REE ratio inside and outside the cells. Interestingly, we also show that there is considerable variation in the uptake of the NPs from cell-to-cell, by a factor of more than 10. We conclude that the NPs enter the cells and remain intact. The large heterogeneity in NP concentrations from cell-to-cell should be considered if they are to be used therapeutically.