Development of Theranostic Nanoparticles; MRI-responsive, thermosensitive drug carriers activated by MRg FUS for local tumour drug release

Our proposed research program is concerned with how to mobilize physical science and engineering innovation in nanoparticle drug carrier design from basic science laboratory to medical application. In order to do this, Prof Miller's chemistry team (Imperial) with expertise in nanoparticle technologies, will collaborate closely with Dr Maya Thanou's pharmaceutical sciences team (Kings) in the design, formulation and characterization of MRI-responsive thermosensitive drug carrier nanoparticles (theranostic ABC nanoparticles) that have the capacity to accumulate in cancerous lesions (fibroids or tumours), in real time post administration in vivo (as observed by MRI). Thereafter, we will collaborate with and make use of the expertise of the research teams of Prof Gedroyc and Dr Stebbing (Imperial, Medicine) to demonstrate that these nanoparticles can then be activated by means of magnetic resonance guided focused ultrasound (MRgFUS) to release drug locally at sites of nanoparticle accumulation within the relevant lesion. This combined process should be able to deliver a powerful anti-cancer effect that also improves radically on local drug bioavailability (specific only to tumours) and drug efficacy while minimizing systemic drug toxicity. Nanoparticle modelling and fluid dynamics studies will then be performed by the team of Prof Xu (Imperial, Chemical Engineering) in order to improve our understanding of the delivery barrier and drug release and uptake process. Thereafter we shall seek to take this understanding to optimize MRgFUS-activated theranostic nanoparticle mediated drug delivery of actives in vivo provided by our healthcare partner Antisoma. We anticipate that Antisoma and our other healthcare partners [the Focused Ultrasound Surgery (FUS) Foundation and MacMillan Nurses] will assist us with the commercialization process thereafter including providing some of their novel anti-cancer compounds for local delivery, to increase efficacy and decrease toxicity.

The proposed research program aims at the development of theranostic nanoparticles for Cancer. Cancer is one of the mostly frequent life threatening diseases. There are more than 293,000 new cases of cancer (excluding non-melanoma skin cancer) diagnosed each year in the UK, and more than 1 in 3 people will develop some form of cancer during their lifetimes. For the first time in the UK, researchers from two leading institutes of teaching and research (Imperial College London and Kings College London) that represent three discrete disciplines (Medicine, Engineering and Chemistry) propose to form a partnership with a London stock exchange-listed biotech company (Antisoma Ltd), a global biomedical charitable foundation (the Focused Ultrasound Surgery Foundation [FUS Foundation]), and a leading UK provider of Cancer care (MacMillan Nurses) to develop and apply smart nanotechnology for the advanced treatment of Cancer. The project aims to enhance the quality of life of all those who suffer from Cancer. Direct beneficiaries: Output and outcomes from the proposed research program will directly benefit the non-academic partners involved with this project. 1 Antisoma; a biotechnology company specialising in the development of novel drugs for the treatment of cancer. The output and outcomes from the proposed research program are certain to be of interest and benefit to big Pharma companies too. 2) The FUS Foundation as a non-commercial collaborator will also immediately benefit from the output and outcomes of the proposed research program. 3) The MacMillan Nurses will benefit through being seen to be a leading medical exponent and champion for leading edge smart nanotechnologies for Cancer treatment. Indirect beneficiaries: Indirectly, 1) data generated will assist in the development of even further novel nanotechnologies for Cancer in a novel area of Cancer research (Nanooncology) 2) millions of cancer patients world-wide will benefit from the development of routine detection and treatment of small size tumours and their metastases without the need for operation, hospitalization and with minimal adverse effects from chemotherapy. The approached described in our proposed research program should be so specific that Cancer lesions will be treated while neighbouring healthy tissues can remain completely unaffected. Consequently the output and outcomes from the proposed research program should substantially improve the effectiveness of cancer chemotherapeutic treatments and provide a substantially enhanced management of the disease. Therefore, the benefits to cancer patients and the NHS should be obvious. Moreover, such smart, drug delivery nanotechnologies applied to Antisoma drugs will position Antisoma with the opportunity to develop new highly competitive cancer therapies and take a position in novel smart, drug delivery nanotechnologies that could render potentially wider ground-breaking changes in cancer therapy, thereby boosting substantially the global competitiveness of this (and potentially other) UK based biotech companies specialising in cancer therapies. All this will all be made possible by the actions of a dedicated core academic team (headed by Prof Miller of Imperial College) carrying out the proposed research program with the assistance and collaboration of the key healthcare partners (Antisoma, FUS Foundation and the MacMillan Nurses) working together in a disciplined process of regular reporting, monitoring, discussing, guiding and advice giving in order to keep the proposed research program to plan. Antisoma will assist with links and networking with other biotech and pharma working in the area of Cancer therapies, and has the means for commercial development of the output and outcomes from the current proposed research program. Clinical enthusiasm for smart nanotechnologies will be boosted in collaboration with the FUS Foundation and MacMillan Nurses who will open the door to the Oncology community.