Abstract
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.
Highlights
Nanoparticles (NPs) offer unique capabilities and applications to healthcare, ranging from therapeutics to diagnostics
We show that the concentration of dopant rare earth elements (REEs) in titania NPs is the same both inside and outside the cells, and are spatially distributed with the titania matrix
We have used a proton microprobe to investigate the integrity of REE-doped titania NPs in individual human cells
Summary
Nanoparticles (NPs) offer unique capabilities and applications to healthcare, ranging from therapeutics to diagnostics. Doping NPs with rare earth elements (REEs) has previously been used. To enhance the effect of x-rays on cancer cells [1, 2], and has many other interesting biosensing applications. The doped titania NPs used in this work were designed for use as radiosensitizers, to improve the efficacy of radiotherapy. Titania NPs can be excited by UV light and are used for photodynamic therapy for surface cancer treatments, but due to the penetration depth of UV light, deep tissues or large tumours cannot be treated by this method. The addition of the REE dopants extend the range of excitation to x-ray energy [3]
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