Targeted iron oxide nanogels for ovarian cancer hyperthermia therapy

Ovarian cancer is the main gynaecological killer of women in the UK with around 7,500 women being diagnosed with ovarian cancer each year. Better treatments are necessary in order to combat the disease and help patients live longer. This project aims to develop a highly novel targeted magnetic nanotherapy that can kill cancer cells in two ways, both through heat and also the release of an anticancer drug. Magnetic nanocarriers are a highly versatile platform for cancer therapy as they can deliver heat and drugs local to the cancer cells. In this project magnetic nano-composites (MNCs) made of an iron oxide
nanostructure core will be developed in the Thanh lab and characterised. Subsequently the iron oxide nanoflowers (cluster of nanoparticles) will then act as templates around which a nanogel shell will be polymerised in the Kamaly lab that will include the following components: a heat responsive element that will lead to the release of olaparib and a targeting ligand that will specifically target ovarian cancer cells. The nanoparticles will be extensively tested for their hyperthermic and magnetic properties in the Thanh lab and subsequently characterised for their size, shape, surface charge, degradation in response to heat and ovarian cancer cell targeting abilities in the Kamaly lab. Furthermore, the synergistic and combinatorial effects of hyperthermia + olaparib therapy will be tested on advanced ovarian cancer cells in vitro. It is hoped that this novel therapy will bridge the gap in multimodal ovarian cancer therapy whereby combinations of imaging and therapeutic agents can be investigated.
The project is proposed to adhere to the following timeline:
PhD yr 1: Synthesis of core MNCs (NT lab) and surface functionalization (NK lab). Nanoparticle characteristion (TEM and DLS)
PhD yr 2: Further characterization of MNCs (Japan, XPS, HRTEM, STEM)
PhD yr 3: In vitro and in vivo investigations of MNCs in Ovarian cancer models.

The production and processing of materials accounts for 15% of UK GDP and generates exports valued at £50bn annually, with UK materials related industries having a turnover of £197bn/year. It is, therefore, clear that the success of the UK economy is linked to the success of high value materials manufacturing, spanning a broad range of industrial sectors. In order to remain competitive and innovate in these sectors it is necessary to understand fundamental properties and critical processes at a range of length scales and dynamically and link these to the materials' performance. It is in this underpinning space that the CDT-ACM fits.

The impact of the CDT will be wide reaching, encompassing all organisations who research, manufacture or use advanced materials in sectors ranging from energy and transport to healthcare and the environment. Industry will benefit from the supply of highly skilled research scientists and engineers with the training necessary to advance materials development in all of these crucial areas. UK and international research facilities (Diamond, ISIS, ILL etc.) will benefit greatly from the supply of trained researchers who have both in-depth knowledge of advanced characterisation techniques and a broad understanding of materials and their properties. UK academia will benefit from a pipeline of researchers trained in state-of the art techniques in world leading research groups, who will be in prime positions to win prestigious fellowships and lectureships. From a broader perspective, society in general will benefit from the range of planned outreach activities, such as the Mary Rose Trust, the Royal Society Summer Exhibition and visits to schools. These activities will both inform the general public and inspire the next generation of scientists.

The cohort based training offered by the CDT-ACM will provide the next generation of research scientists and engineers who will pioneer new research techniques, design new multi-instrument workflows and advance our knowledge in diverse fields. We will produce 70 highly qualified and skilled researchers who will support the development of new technologies, in for instance the field of electric vehicles, an area of direct relevance to the UK industrial impact strategy.
In summary, the CDT will address a skills gap that has arisen through the rapid development of new characterisation techniques; therefore, it will have a positive impact on industry, research facilities and academia and, consequently, wider society by consolidating and strengthening UK leadership in this field.