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

癌症是全球第二大死亡原因，只有50%的确诊患者存活超过10年。由于缺乏特异性、药物的溶解度和分布差、不利的药代动力学和对健康细胞的毒性（其导致严重的副作用），使用传统化学治疗剂的治疗受到阻碍。癌症治疗诊断学领域已经产生了大量的兴奋，由于创新的能力，增加治疗选择的基础上，特定的分子疾病的标志，提高预见可能的不良反应，和新的方法来经验性地监测反应的治疗。靶向药物递送系统被探索用于设计能够选择性递送毒性药物同时还能够检测递送和药物释放后的命运的智能疗法。在这个项目中，我们的目标是减少脱靶毒性和增加治疗药物在靶器官中的浓度。将有效的癌症治疗与靶向能力相结合，再加上成像和治疗效率，将是癌症纳米医学领域的独特补充。通过实现这些目标，这项研究将有助于成功的概念验证疗法，这将大大减少脱靶毒性并提高整体治疗成功率。这个跨学科项目将利用剑桥大学多个部门的知识，并进一步利用日立的专业知识。该项目将涉及多模式纳米载体系统的合成，该系统使用多孔聚多巴胺（PDA）纳米载体，用螯合剂修饰，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，并含有官能团，以结合癌细胞特异性靶向剂，用于难以治疗的癌症。靶向药物将与丹尼尔·穆诺兹-埃斯平博士的小组合作进行探索。纳米载体系统将在每个阶段使用金标准和最先进的新技术进行评估。将进行小动物PET研究，以获得有关生物分布的重要信息。该项目的主要成果将是推进难以治疗的癌症的新疗法。从长远来看，该研究将通过增加到达肿瘤部位的药物的浓度和特异性，有助于改善患者的预后和生活质量。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的治疗解决方案。研究人员将受益于将在这个跨学科项目中探索的新的科学方法和工程方法。该项目优化了诊断和治疗，并有助于创造新的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，并在生物纳米技术，药物输送，放射学和医学成像等动态领域的帮助下。

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.