SMARTdrugs_Supramolecular agents as radiotheranostic drugs

从癌症患者生物标志物表达的定量和表征的诊断应用，到分子靶向放射性核素治疗，放射性药物处于现代个性化医疗的前沿。SMARTdrugs的激进的长期愿景是利用超分子化学尚未开发的潜力，创造一种新的治疗方法-放射治疗诊断学-将诊断和治疗放射性核素联合收割机结合在一种化合物中。以主客体超分子配合物和分子互锁分子的自组装为骨架构建超分子放射治疗药物，将为放射治疗药物的合成提供一种突破传统药物化学概念的新方法。SMARTdrugs将建立一个概念验证，证明非共价系统在设计具有定制药代动力学的多功能放射治疗剂中的实用性，以及它们在具有挑战性的药物递送场景中的应用，包括靶向递送到肺癌和脑癌。我们的三大目标：目标1 -使用非共价键合开发新的化学景观，以创建用于癌症特异性治疗诊断的功能化超分子化合物目标2 -阐明超分子放射治疗诊断与决定体内药物疗效的复杂肿瘤微环境之间的关键关系目标3 -进行头对头研究，以建立超分子化学是经典放射性药物设计的可行替代方案的原则长期目标是为放射治疗设计建立新的化学景观，并促进这种新技术的临床转化。成功的实验将为在更广泛的药物递送和治疗诊断学背景下利用超分子化学奠定基础，并为研究细胞到整个生物体水平的生物相互作用奠定基础。

From diagnostic applications in the quantification and characterisation of biomarker expression in cancer patients, through to molecularly targeted radionuclide therapy, radiopharmaceuticals are at the frontline of modern personalised medicine. The radical long-term vision of SMARTdrugs is to harness the untapped potential of supramolecular chemistry to create a new class of therapies - radiotheranostics - which combine both diagnostic and therapeutic radionuclides in one compound. By using the self-assembly of host-guest supramolecular coordination complexes and molecularly interlocked molecules as scaffolds for creating supramolecular radiotheranostic drugs, new methodsfor radiotheranostic synthesisthat break away from conventional medicinal chemistry concept will be introduced. SMARTdrugs will establish a proof-of-concept demonstrating the utility of non-covalent systems in the design of multifunctional radiotheranostic agents with tailored pharmacokinetics, and their application in challenging drug-delivery scenarios including targeted delivery to cancers of the lung and brain. Our 3 main objectives: Objective 1 – Develop new chemical landscapes using non-covalent bonding to create functionalised supramolecular compounds for cancer-specific theranostics Objective 2 – Elucidate the key relationships between supramolecular radiotheranostics and the complex tumour microenvironment that determine drug efficacy in vivo Objective 3 – Perform head-to-head studies to establish a proof-of-principle that supramolecular chemistry is a viable alternative to classical radiopharmaceutical design The long-term goal is to establish a new chemical landscape for radiotheranostic design, and to facilitate clinical translation of this new technology. Successful experiments will lay the foundations for exploiting supramolecular chemistry in the wider context of drug delivery and theranostics, and for studying biological interactions at the cellular to whole-organism levels.