Title: Terahertz skinometer for improved cancer prevention and treatment
Funder: Engineering and Physical Sciences Research Council

Abstract: The incidence of skin cancer in the UK and globally is increasing. There are two main types of skin cancer: melanoma and non-melanoma skin cancer. Basal Cell Carcinoma (BCC) is a non-melanoma skin cancer, and is the most common type (> 80%) of all UK skin cancer cases. It is well known that applying sunscreen helps to protect the skin from the sun but many people are unaware of the need for UVA (315-400 nm) as well as UVB (280-315 nm) protection. Although lower in energy than UVB, the amount of UVA reaching the earth's surface is 30 times more than for UVB. Furthermore, UVA penetrates the skin more deeply, contributing to both carcinogenesis and skin aging via oxidative stress pathways. One of the most common UVA filters is avobenzone, as it is industrially cheap and thus affordable to the consumer. However, it is now well-established that avobenzone photodegrades, which is a serious concern. In this project, a highly interdisciplinary team consisting of investigators at the University of Warwick in the Departments of Physics, Chemistry, Life Sciences and Medicine, as well as industry partners from Lubrizol (major skin-care provider) and TeraView Ltd (major terahertz (THz)-based instrument provider) will join forces to attack the problem of increasing skin cancer 'prevention' and 'treatment' using a multi-pronged approach. We will improve skin cancer prevention by developing a new UVA, nature-inspired, sunscreen offering longer lasting and more photostable protection than existing sunscreens. To achieve this, we will repurpose the photoprotection mechanisms of other living organisms, specifically those of cyanobacteria and microalgae. These organisms protect themselves from radiation by producing mycosporine-like amino acids (MAAs), a family of molecules which are strong UVA absorbers and are ideal candidates for sunscreen agents, owing to their dual action as UVA filter and antioxidant. We recognise that sunscreens are composed of a UV filter blended with a moisturiser (emollient); this can make up to 80% of the composition of the sunscreen. We also recognise that sunscreens are applied to skin. Therefore, to optimise the sunscreen composition, we will develop a revolutionary characterisation tool, the 'THz skinometer', which is able to measure parameters of skin in vivo that other techniques cannot. In this way, we will determine the best UV filter/emollient blend. We will investigate whether different skin conditions such as eczema and psoriasis will benefit from a different emollient blend. THz radiation is non-ionising, using low power levels such that thermal effects are insignificant and consequently safe for in vivo imaging of humans as well as non-destructive testing of materials. It is very sensitive to intermolecular interactions such as hydrogen bonds, and probes molecular processes (eg vibrations, chemical reactions) that occur on picosecond (millionth millionth of a second) timescales. In this project we will employ THz techniques to evaluate the effectiveness of emollients and sunscreens in vivo with a view to developing a single sunscreen that covers both the UVA and UVB regions of the solar spectrum. Furthermore, as a powerful additional feature of our invention, we will also use our THz skinometer to improve the surgical removal, or 'treatment', of skin cancers such as BCC, which often spread out beneath the surface of the skin such that their entirety cannot be detected until surgery. The THz skinometer will be designed to accurately characterise skin in vivo such that it will be able to determine the likely extent of any tumour beneath the surface. In this way, we will identify the full extent of the tumour prior to surgery which will improve skin grafting planning as well as reduce the likelihood of missing any tumour and tumour recurrence. Thus by attacking skin cancer through 'prevention' as well as 'treatment', we aim to reduce 'incidence' and 'morbidity' of skin cancer in the UK & globally.

Lay abstract: The overarching vision of this proposal is to develop a novel, and highly portable instrument, the 'THz skinometer', that will transform the way skin hydration is measured with far-reaching benefits. The skinometer will be taken to a skin clinic to be tested on patient volunteers. In particular, we will show how our skinometer can be applied to develop next generation nature-inspired sunscreen/moisturiser formulations, and to potentially improving the detection of subclinical cancer. To achieve this vision, five objectives will be pursued within the 36 month timeframe of the proposal. These objectives are as follows: 1. Design and build a THz skinometer to enable non-contact and contact measurements of skin with controllable contact pressure. 2. Develop theoretical models to accurately extract skin properties including the skin hydration profile and water diffusion from the THz skinometer data. 3. Determine the optimum mycosporine amino acid for effective UVA protection, through synthesis and transient absorption spectroscopy measurements. 4. Use the THz skinometer to evaluate the hydration of areas of eczema, psoriasis, skin grafts and skin cancer scar sites and optimise moisturisation strategies in these skin types. Determine the optimum emollient for use in sunscreen formulations and investigate if the sunscreen can be tailored for different skin types. 5. Apply the THz skinometer to investigate if patient invariant THz parameters can be found for detection of subclinical skin cancer. The five objectives will be met through the execution of four highly complementary work-packages. These work-packages (with associated tasks) comprise a unique combination of experiment and theory, and are focused on instrumentation development, algorithm development, femtosecond pump-probe measurements, molecular synthesis and in vivo skin measurements. In short, our objectives bring together both prevention and treatment of skin cancer into one project. We will uncover some fundamental science and develop new instrumentation and algorithms in the process that will be also beneficial to other healthcare related applications in the future.

Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS;SKIN