Neuro-oncological precision nanomedicines

According to the world health organisation, the incidence of brain tumours has been rising steadily (up to forty percent) since the late 1970s. World-wide deaths in 2012 were recorded as 189,382 and are predicted to rise by a further twenty-five percent by 2020. Brain tumours are the most common solid tumour in children and the second most common cancer after leukaemia representing twenty-five percent of all primary paediatric tumours, the leading cause of cancer death. Despite the advances in imaging and multi- modality therapy with neurosurgery, radiotherapy and conventional cytotoxic chemotherapy, outcomes for high-risk brain tumours have improved little in the last two decades. When treatments are effective, they are associated with both acute and long-term significant treatment-related side effects. One of the chief obstacles hindering effective therapy for brain tumours is that the brain is very much isolated from the rest of the body with well-gated barriers controlling the trafficking of molecules and macromolecules in and out. In particular, the interface between the circulatory system and the brain tissues, (the blood-brain barrier (BBB) is the largest barrier by surface area, and allows short distance between blood and neural tissue. On top of this, one of the most critical limitations for cancer therapy is our inability to direct anticancer drugs to cancerous cells maximising killing and minimising side effects (often worse than the disease itself). This is due to the fact that cancer cells are the same healthy cells gone wrong and hence share many similarities with the good cells complicating detection and targeting.We propose here the design of ultra-small carriers (as small as a virus and 100 times smaller than cancer cells) that will be equipped with unique chemical signature to target almost exclusively the BBB, cross it, and target brain cancer cells. These nanocarriers will also be able to carry different drugs and deliver them right inside the cells where the drug is most effective.

This proposal will directly tackle a major challenge currently unmet in the clinic with an entirely new way to produce drug excipients. The impact on several clinical settings can be enormous if the herein proposed research proves successful. Besides cancer and infections also neurodegenerative diseases and immunological disorders could be tackled. Mainly due to the biodegradability of materials suggested, the outcomes can transform medicine to administer drugs far more efficiently than today with all the excipients being completely degradable and vanishing traceless from the body. Nanotechnology as a whole is facing big expectations from the general public in terms of revolutionising healthcare for all people, but besides the challenge this is also a great driving force for us and motivates us to get engaged with the general public to discuss fears and expectations.
Drug delivery needs to be designed effectively. This includes an efficient drug itself but a very efficient administration method so that the drug and its excipients are well perceived by the targeted cells only and do not interfere with other parts and cycles of a living organism. Developing new excipients that do not hamper a drugs performance while not causing a wide range of side-effects is thus essential for modern nanomedicine. This proposal outlines research for an entirely new way to design nanoscopic drug carriers whilst using established models of carrier formation. This combination promises successful carrier formation with clinical trials to be able to follow soon. We either use FDA/MHRA approved chemicals or some that have the potential to through the approval process quickly. We also recognise, as stated on the EPSRC delivery plan, that is very important to demonstrate the impact of our research by involving business collaborators. We chose to collaborate with Somanautix ltd, and AbbyMed LLC. They are both small enterprises, and we deliberately made this decision with the aim to increase the impact on UK economy made with taxpayers funds. If this project will be successful we will make this investigator-led idea into a preclinical/clinical development program together with Somanautix ltd. This will require Somanautix to complete two steps (i) hire new working forces and (ii) generate new intellectual properties. These steps are the pillars to build a strong scientific economy in the UK.