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7500名女性被诊断患有卵巢癌。为了对抗这种疾病，帮助患者延长寿命，更好的治疗是必要的。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，一种是通过加热，另一种是释放抗癌药物。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传递到癌细胞的局部。在这个项目中，由氧化铁纳米结构核心制成的磁性纳米复合材料（MNCs）将在Thanh实验室开发并表征。随后，氧化铁纳米花（纳米粒子簇）将作为模板，在其周围将在Kamaly实验室聚合纳米凝胶外壳，该外壳将包括以下成分：导致奥拉帕尼释放的热响应元件和特异性靶向卵巢癌细胞的靶向配体。这些纳米颗粒将在Thanh实验室进行广泛的高温和磁性测试，随后在Kamaly实验室对它们的大小、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，热疗+奥拉帕尼治疗的协同和联合效应将在体外对晚期卵巢癌细胞进行试验。希望这种新的治疗方法将弥合多模式卵巢癌治疗的差距，从而研究成像和治疗药物的组合。该项目建议遵循以下时间表：博士一年级：核心MNCs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）博士二年级：MNCs的进一步表征（日本，XPS， HRTEM， STEM）博士三年级：MNCs在卵巢癌模型中的体外和体内研究。

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.