Oxidation-sensitive nanomaterials for treatment of immune diseases

We generally consider our immune system as our protector, destroying germs and preventing an infection from killing us. However, when the immune system works incorrectly it can cause diseases itself (autoimmune diseases) including asthma, rheumatoid arthritis and multiple sclerosis. Additionally, as our understanding of immunology has improved we have found that the immune system is involved in many more diseases that previously thought including cancer, stroke and even physical injuries.

Many of these diseases cannot be cured and are chronic and degenerative, with each occurrence of symptoms resulting in further damage. To prevent flare ups and minimise further damage we treat patients continually whether needed or not, often resulting in severe side effects from the drugs. Ideally, a patient would take their medicine each day and it would do nothing unless needed. In the event of disease progression, a drug would be released treating the symptoms and minimising disease progression. At the same a visual signal, e.g. a change in urine colour, would alert the patient to the elevated disease state allowing them to take additional medication or contact a doctor.

Here we aim to develop a range of new materials that can act as carriers for drugs. Under normal, "healthy", conditions these carriers will circulate for a few hours/days before being excreted harmlessly via urine/faeces. On exposure to the disease environment they will respond by releasing a drug capable of treating the targeted disease.

We aim to develop a new range of materials that can respond to the biochemical environment found at sites of inflammation with the intention of developing new therapeutics for chronic immune disease. Although the research proposed here is fundamental, the later applications have the potential for significant impact across the UK and the wider world. Several key areas of impact have been identified.

Societal:
For patients with immune disease the proposed research will provide great benefit by producing new materials for advanced therapies that are capable of reducing the frequency of medication, severity of symptoms and occurrence of side effects. Consequently, they will be benefit from decreased disease progression and an overall increase in quality of life. Additionally, the wider public will benefit from increased education about the causes of immune diseases and how we are trying detect and treat them through our planned outreach activities.

Immune disease prevalence is increasing and will continue in our aging population. The World Health Organization estimates that over 100,000 disability-adjusted life years were lost to rheumatoid arthritis alone in the UK in 2012. This results in a considerable burden on the NHS and the UK economy as a whole. Reducing the impact of such diseases at a patient level will have a knock-on effect at a national (and international) level by increasing productive working-life.

Industrial and economic:
The UK is host to some of the largest pharmaceutical companies in the world (e.g. AstraZeneca, GSK, MedImmune) with a average sector-wide trade surplus of over £1bn/year for the last decade. At the same time, immunotherapy is a growth area with an estimated market value of $70bn by 2020. The development of new materials capable of controlling immunotherapy more specifically will allow the UK to remain at the forefront of this market with the resulting economic benefits.

Although not directly by this proposal, if funded the host institution has committed to provide a PhD studentship to work on this project. This student will be highly trained in the synthesis and analysis of advanced polymeric materials, an area that the UK is world-leading academically and industrially (e.g. AkzoNobel, Scott Bader, Lubrizol), allowing further benefit to the UK economy. The importance of multidisciplinary research to the successful development of new healthcare technologies has been stressed within the Maxwell review. The wider project that this proposal falls within is inherently multidisciplinary and the students involved will also receive training in biological techniques such as cell culture and in vitro bioassays.