Confocal spectroscopy for cell 3D microthermometry

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One in two people will be diagnosed with cancer during their lifetime, presenting a significant challenge to the UK goal of "staying healthy for longer". For some cancers, therapeutic innovations have increased survival, but for other cancers, such as brain cancer, outcomes have changed little in 20 years. A topic of increasing interest in the cancer research community is the critical role of metabolism in cancer cell behaviour. The Warburg effect, a metabolic switch from oxidative to glycolytic metabolism in cancer cells, has been documented for over decades, but much remains unknown about the nature and significance of cancer cell metabolism. The intrinsic pyrogenic substances secreted by tumour cells induce distinct hyperthermia in the temperature range of 37 to 42 C. Simultaneously, different parts of the cell can be at different temperatures, with mitochondria more than 10 C above basal temperature.We need to investigate fundamental unknowns about cancer cell metabolism, its role in cancer growth and the potential of targeting more metabolically active regions within cancer for therapy. Significantly, there is increasing awareness that this needs to be done in the context of intact cancer tissue, where the cancer cell interactions with the cellular microenvironment can be observed. Cancer cell-microenvironment interactions influence cancer cell biology and are not effectively modelled using in vitro cancer cell cultures. Crucially, then, cancer cell metabolism must be interrogated in tissue slice culture, and ultimately in rodent models, for which we need innovative technologies as proposed here.For this, it is necessary to have an imaging technique capable of working in three dimensions in thick tissue, and able to provide the temperature distributions in the cancer environment. This can be achieved by using luminescent nanoparticles as probes. Such nanoparticles can be 500 times smaller than a red blood cell, and when they are excited with light of a wavelength ("colour"), they will re-emit light in a different wavelength. The analysis of this re-emitted light can provide information about the temperature of its environment. Importantly, certain wavelengths can propagate longer in tissue without being attenuated, which can be used for obtaining information from inner areas. This will enable the 3D reconstruction of the map of temperatures.