Molecularly engineered iron-catalysed cancer nanomedicine

分子工程铁催化癌症纳米药物

• 批准号: 2865083
• 金额: --
• 依托单位: Swansea University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2865083
• 关键词: Molecularly; engineered; iron; catalysed; cancer

Cancer immunotherapy is revolutionizing cancer treatment. However, the current immunotherapy drugs, which target immune checkpoint blockade using monoclonal antibodies (mAb), only benefit a relatively small fraction of cancer patients, and the treatments are extremely expensive. Nanotechnology, chemical science approaches and advanced biomaterials will play a critical role in the development of more effective immunotherapy treatments that can help more patients. One of the promising areas is in the development of small-molecule inhibitors of immune checkpoints but these efforts are still in early stages. mAb-based immune checkpoint inhibitors targeted to the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Signalling Pathway have been particularly effective in clinical trials. However, specific delivery of the drugs to the tumour microenvironment (TME) and modulating the immunosuppressive TME to improve the response to the therapy is very challenging. Nanomaterials are uniquely suited to overcome these challenges as they can be rationally designed to act as drug delivery vehicle and to trigger additional anti-tumour responses. This PhD project will harness a versatile platform technology that encapsulating iron oxide nanoparticles inside phospholipid micelles (mIONPs) enables effective in vitro and in vivo delivery of the anti-cancer drugs to the tumour cells. The construct provides imaging and magnetic features to locate, guide and study cellular specificity and biodistribution and therapeutic responses. In this construct intrinsic cancer therapy is also provided by its iron content and enzyme-like properties.The PhD project seeks to develop new molecular tools (small-molecules and iron nanostructured materials), bioorthogonal catalysis and bioconjugation protocols to create an innovative chemoimmunotherapeutic iron-loaded lipid nanoparticle. The construct will have chemically programmed features for immune checkpoint blockade targeting the PD-1/PD-L1 pathway, with the potential to overcome immune-suppression in the TME and to trigger iron-catalysed cancer cell death. Ultimately, the goal is creating a nanomedicine platform that significantly improves current immunotherapy and chemoimmunotherapy, and with potential for translation into clinical practice.

癌症免疫疗法正在给癌症治疗带来革命性的变化。然而，目前使用单抗(MAb)靶向免疫检查点阻断的免疫治疗药物只对相对较少的癌症患者有效，而且治疗非常昂贵。纳米技术、化学科学方法和先进的生物材料将在开发更有效的免疫疗法方面发挥关键作用，这些疗法可以帮助更多的患者。有希望的领域之一是开发免疫检查点的小分子抑制剂，但这些努力仍处于早期阶段。针对程序性细胞死亡-1/程序性细胞死亡-配体1信号通路的基于单抗的免疫检查点抑制剂在临床试验中特别有效。然而，将药物特定地输送到肿瘤微环境(TME)并调节免疫抑制TME以提高对治疗的反应是非常具有挑战性的。纳米材料特别适合于克服这些挑战，因为它们可以被合理地设计为药物输送载体，并引发额外的抗肿瘤反应。这个博士项目将利用一种通用的平台技术，将氧化铁纳米颗粒封装在磷脂胶束(MIONPs)中，从而能够在体外和体内有效地将抗癌药物输送到肿瘤细胞。该结构提供了定位、指导和研究细胞特异性、生物分布和治疗反应的成像和磁学特征。在这一构建中，铁含量和类酶特性也为内在癌症治疗提供了支持。PHD项目致力于开发新的分子工具(小分子和铁纳米结构材料)、生物正交催化和生物偶联方案，以创建创新的化学免疫治疗载铁脂质纳米颗粒。该构建体将具有化学编程功能，针对PD-1/PD-L1途径的免疫检查点阻断，有可能克服TME中的免疫抑制，并触发铁催化的癌细胞死亡。最终，我们的目标是创建一个纳米医学平台，显著改进目前的免疫治疗和化学免疫治疗，并具有转化为临床实践的潜力。