Targeted iron oxide nanogels for ovarian cancer hyperthermia therapy

卵巢癌是英国女性的主要妇科杀手，每年约有7，500名女性被诊断患有卵巢癌。更好的治疗是必要的，以对抗疾病，帮助病人活得更长。该项目旨在开发一种高度新颖的靶向磁性纳米疗法，可以通过两种方式杀死癌细胞，即通过加热和释放抗癌药物。磁性纳米载体是一种高度通用的癌症治疗平台，因为它们可以将热量和药物局部递送到癌细胞。在该项目中，由氧化铁纳米结构核心制成的磁性纳米复合材料（MNC）将在Thanh实验室开发并表征。随后，氧化铁纳米花（纳米颗粒簇）将作为模板，在Kamaly实验室中将聚合纳米凝胶壳，该壳将包括以下组分：将导致奥拉帕尼释放的热响应元件和将特异性靶向卵巢癌细胞的靶向配体。这些纳米颗粒将在Thanh实验室中对其高温和磁性进行广泛测试，随后在Kamaly实验室中对其尺寸，形状，表面电荷，热降解和卵巢癌细胞靶向能力进行表征。此外，将在体外对晚期卵巢癌细胞测试热疗+奥拉帕尼疗法的协同和组合效应。希望这种新的治疗方法将弥合多模式卵巢癌治疗的差距，从而可以研究成像和治疗药物的组合。该项目建议遵循以下时间轴：博士第一年：核心MNC的合成（NT实验室）和表面功能化（NK实验室）。纳米颗粒表征（TEM和DLS）博士第2年：进一步表征的MNC（日本，XPS，HRTEM，STEM）博士第3年：在体外和体内研究卵巢癌模型中的MNC。

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.