A novel radiolabelled multimodal nanocarrier system for tracking the delivery of therapeutic drugs and radionuclides in hard-to-treat cancers

一种新型放射性标记多模式纳米载体系统，用于跟踪难治性癌症中治疗药物和放射性核素的输送

• 批准号: 2276769
• 金额: --
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2276769
• 关键词: novel; radiolabelled; multimodal; nanocarrier; system

Cancer is the second leading cause of death worldwide, with only 50% of diagnosed patients surviving a more than 10 years. Therapy using traditional chemotherapeutics is hindered due to lack of specificity, poor solubility and distribution of the drugs, unfavourable pharmacokinetics, and toxicity to healthy cells which results in severe side effects. The field of cancer theranostics has generated a vast amount of excitement due to the innovative ability to increase therapeutic selection on the basis of specific molecular disease hallmarks, improved foresight of possible adverse effects, and novel methods to empirically monitor response to the therapy. Targeted drug delivery systems are explored for the design of smart therapies capable of selective delivery of toxic drugs while also enabling detection of the delivery and post-drug release fate. In this project, we aim to reduce off-target toxicities and increase concentrations of therapeutic drugs in target organs. Combining effective cancer treatment with targeting abilities, paired with imaging and therapeutic efficiency will be a unique addition to the field of cancer nanomedicine. By achieving these objectives, this research will contribute a successful proof-of-concept therapy, which will greatly reduce off-target toxicities and increase overall therapy success. This interdisciplinary project will harness knowledge across numerous departments at the University of Cambridge, and further expertise from Hitachi. The project will involve the synthesis of a multimodal nanocarrier system using porous polydopamine (PDA) nanocarriers decorated with chelating agents for binding radionuclides for imaging, capable of embedding the drug molecules within their cores and containing functional groups to bind cancer cell specific targeting agents for hard-to-treat cancers. Targeting agents will be explored in collaboration with Dr Daniel Munoz-Espin's group. The nanocarrier system will be assessed at each stage using both gold standard and novel state-of-the art technologies. Small animal PET studies will be carried out to gain important information on biodistribution. The main outcome from this project will be the advancement of novel treatments for hard-to-treat cancers. In the long term, the research will contribute to the improvement of patient outcomes and quality of life by increasing the concentration and specificity of drugs that reach the tumour site. In the short term, clinicians, patients, regulatory authorities, and other stakeholders will benefit from the early involvement for a novel therapeutic solution. Researchers will benefit from the new scientific approaches and engineering methods that will be explored in this interdisciplinary project. The project optimises diagnosis and treatment and aids in the creation of novel therapies and approaches to drug delivery and targeted medicine. This project is aligned with the EPSRC's clinical technologies research area, with the help of the dynamic fields of bionanotechnology, drug delivery, radiology, and medical imaging.

癌症是全球死亡的第二大原因，只有50％的诊断患者幸存了10年以上。由于缺乏特异性，溶解度和药物分布，不利的药代动力学以及对健康细胞的毒性，因此使用传统的化学治疗受到阻碍，从而导致严重的副作用。由于特定的分子疾病标志，提高了治疗选择的能力，对可能的不良反应提高了治疗选择，以及通过经验监测对治疗的反应的新方法，因此癌症治疗领域引起了极大的兴奋。探索了有针对性的药物输送系统，以设计能够选择性递送有毒药物的智能疗法，同时还可以检测到输送和药物后释放命运。在这个项目中，我们旨在减少靶向器官中脱靶毒性并增加治疗药物的浓度。将有效的癌症治疗与靶向能力相结合，与成像和治疗效率相结合将是癌症纳米医学领域的独特补充。通过实现这些目标，这项研究将为成功的概念验证疗法做出贡献，这将大大降低脱靶毒性并增加整体治疗的成功。这个跨学科项目将利用剑桥大学众多系的知识，并从日立的进一步专业知识。该项目将涉及使用多孔聚酰胺（PDA）纳米载体合成多模式纳米载体系统，该纳米载体装饰有螯合剂，用于结合放射性核素进行成像，能够将药物分子嵌入其核心内，并包含功能组，并包含特定于癌细胞的特定于癌细胞的靶向器，以将特定于癌细胞的靶向器粘合到硬性上。针对代理商将与丹尼尔·穆诺兹·埃斯皮（Daniel Munoz-Espin）博士合作探索。纳米载体系统将在每个阶段使用黄金标准和新型最先进的技术进行评估。小型动物宠物研究将进行，以获取有关生物分布的重要信息。该项目的主要结果将是对难以治疗的癌症的新型治疗方法的发展。从长远来看，这项研究将通过增加到达肿瘤部位的药物的浓度和特异性来改善患者结局和生活质量。在短期内，临床医生，患者，监管机构和其他利益相关者将受益于早期参与新型治疗解决方案。研究人员将从这个跨学科项目中探讨的新科学方法和工程方法中受益。该项目优化了诊断和治疗，并有助于创建新型疗法和药物输送和靶向药物的方法。该项目与EPSRC的临床技术研究领域保持一致，并借助Bionanotechnology，药物输送，放射学和医学成像的动态领域。