Air Pollution Nanoparticles

Can nanoparticles from air pollution get into your brain and cause damage?

The World Health Organization (WHO) estimates that air pollution is responsible for up to 7 million deaths per annum world-wide, and there is growing evidence that air pollution nanoparticles (also called ‘ultrafines’), can enter into the brain. In a pioneering study from September 2016, air pollution nanoparticles (NPs) were found in the human brain by digesting tissue, and extracting NPs with strong magnets, while in early in 2017, epidemiological studies associated NPs with increased dementia risk. However, what is currently lacking is our fundamental understanding of how NPs enter the brain and how this could cause detrimental effects. Establishing if there any mechanistic links between NPs and neurodegeneration is vital, as disorders like dementia are becoming increasingly prevalent in our ageing society, and environmental causes are contested.
Below is a selection of preliminary data I have been working on recently which investigates the interaction of nanoparticles with brain cells and tissue.

Figure 1: A. Single human cell which has internalised TiO2 NPs. Here the concentration of NPs inside cells is directly measured using X-ray analysis. B. NPs incubated with living mouse brain slices are distributed through the tissue, possibly more concentrated in blood vessels. Transmission Electron Microscopy (TEM) image (middle) shows the detailed structure of the blood brain barrier. Quantum dots (QD), which fluoresce brightly, are in the cytoplasm of individual cells within the tissue. C. TEM image of NPs inside a SH-SY5Y neural cell. D. Shows the oxidative stress that NPs induce when incubated with brain slices, measured by DCFDA that fluoresces in contact with free radicals. Microglia activation is measured by fluorescent isolectin-IB4, shown here concentrated around plaques E. I solubilise air pollution NPs from filters collected from Marylebone Road. TEM image of a NP, while Infra-Red spectroscopy shows organics/ions/hydrocarbon peaks in the solubilised material.

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Nanoparticle Telomere Probes

Can we tell how old a cell is using nanoparticles?

Telomeres are like biological clocks located at the ends of chromosomes. Each time a cell divides a little section of the telomere is chopped off, until eventually there is nothing left and the cell stops dividing. In other words, the cell gets old.

Techniques to analyse human telomeres are imperative in studying the molecular mechanism of cell ageing and related diseases. Two important aspects of telomeres are their length in DNA base pairs, and their biophysical nanometer dimensions. However, there are currently no techniques that can simultaneously measure these quantities in an individual cell nucleus. Here, we develop and evaluate a novel telomere “dual” gold nanoparticle-fluorescent probe simultaneously compatible with both X-ray fluorescence (XRF) and super resolution microscopy (dSTORM). Using silver enhancement, we show that GNPs locate at telomere sites within nuclei. We then analyse individual nuclei with micro-XRF, quantifying the gold content in each nucleus along with uncertainties associated with the technique. In parallel, we use dSTORM to measure the nanometer spatial dimensions of individual telomeres. We discuss the limitations of this method and how it could be more generally used to quantify components of cells.

Figure 1: a) schematic showing our novel probe for telomere repeat DNA, consisting of a gold nanoparticle, an anti-telomere PNA probe and an alexa647 super resolution dye molecule. b) Six individual human cells (circled in green) are shown stained with the probe and analyzed with X-ray spectroscopy The image shows the concentration of gold atoms, and so measures how many GNPs there are in each cell. c) Fluorescent images of human chromosomes (blue) with telomeres labelled with the probe (red – 4 per chromosome) and a super resolution image (telomeres in white with a yellow ring).

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Nanoparticles in cancer treatment

Can nanoparticles be used to treat cancer and other diseases?

Nanoparticles can enter human cells, which opens up the intriguing possibilities of using them to deliver drug payloads specifically to different types of cells in the body. This has particular applications in cancer, where often a cancer drug alone is quite toxic, but when encapsulated in a nanoparticle, becomes harmless - until of course it gets to the cancer cell. The challenge therefore, is designing nanoparticles which are non-toxic in themselves, but can be targeted to cancer cells. Below are a few examples of my work, where I have been quantifying the way nanoparticles accumulate in human cells. In particular, I have specialised in using radiotherapy with nanoparticles to enhance the dose of the radiotherapy treatment. The potential benefits to patients are less side effects to normal tissue, and shorter treatments times.

Chemical imaging of titanium nanoparticles in human cells

Figure 1: The location is shown of the NPs within the cells, and cell-to-cell variation of concentration of NPs in cells. A. An optical image shown alongside elemental maps of the same cell. Here, the NPs have localized around the nucleus (but not entered it), and the rare earth signals co-localise with the titanium signal. B. Example of the variation in the quantity of NPs in individual cells. From these images it is clear that each cell has a different concentration of Ti and REE within it compared to its neighbour. C. This variation was quantified in cells (N=40) by using the Ti/P ratio from the PIXE signal (Jeynes et al. 2016 Nanotechnology)

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Related Projects

The seedcorn projects are funded by the Wellcome Trust Centre of Biomedical Modelling and analysis and encourage multi-disciplinary projects across the University of Exeter and beyond.
Below are the projects that I am involved with with results and images soon to follow.

Modelling Phagocytosis in white blood cells

This is a collaboration with David Richards, who is also a fellow Centre for Biomedical Modelling and Analysis. Here, we are taking time-lapse microscopy images of white blood cells engulfing latex beads so that the mechanics of the process can be modelled. The project aims to model and simulate on the underlying processes by which the immune system copes with invading organisms.

Vibrational spectroscopy (FTIR and Raman) imaging of plaques in Alzheimer's

Differences in recovery between muscle in young and old volunteers