Targeted iron oxide nanogels for ovarian cancer hyperthermia therapy

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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.