EPSRC IRC in Targeted Delivery for Hard-to-Treat Cancers

虽然大多数癌症的存活率在过去40年里翻了一番，但难治性癌症的存活率低于14%。为了抗击这些癌症，需要针对多个途径(免疫/炎症、新生血管生成、细胞复制)，这就需要一种多式递送方法，这种方法不仅会增加到达靶点的治疗剂的数量，而且还会增加治疗剂的范围。该IRC将通过以下方式应对这一挑战：(I)基于金属有机框架和有机笼子的递送工具，其有效载荷能力显著提高；以及(Ii)基于凝胶和电泳泵的植入式/可注射递送平台，可增强药物通过血脑屏障的渗透性。通过将这两种方法结合起来，我们将实现到达肿瘤部位的药物数量和范围的一步改变。两个交叉的翻译活动，即材料输送和添加剂制造以及验证，将考虑从递送系统的概念到其临床应用的整个链条，从而导致对靶向药物递送问题的整体方法。拟议的研究计划建立在治疗科学的机构级倡议的基础上，并与CRUK以及药物开发方面的国家实验室和行业领先者建立了密切的联系。参与IRC的跨学科团队包括来自五所大学的小组，他们的专业知识从材料合成和表征，到设备工程和制造，再到药理学和癌症，并将带来超出靶向药物输送领域的科学突破。经济和社会影响将通过市场分析、行业反馈和对翻译风险的内嵌预期的联合方法来交付和衡量。最终用户和利益攸关方的参与最早将在准备第二轮提案时开始，这将在指导IRC的整个生命周期中发挥关键作用。

While the survival rate for most cancers has doubled over the last 40 years, hard-to-treat cancers show survival rates below 14%. To combat these cancers, multiple pathways (immune/inflammatory, neoangiogenic, cell replication) need to be targeted and this necessitates a multimodal delivery approach that will increase not only the amount but also the range of therapeutic agents that reach the target site. This IRC will address this challenge by developing (i) delivery vehicles that are based on metal organic frameworks and organic cages and show substantially increased payload capacity, and (ii) implantable/injectable delivery platforms that are based on gels and electrophoretic pumps and enhance drug penetration through e.g. the blood-brain barrier. By combining these two approaches, we will achieve a step change in the amount and range of drugs that reach the tumour site. Two crosscutting translational activities, on material delivery & additive manufacturing and on validation, will consider the whole chain from the conception of the delivery system to its clinical application, leading to a holistic approach to the problem of targeted drug delivery. The proposed research program builds on an institutional-level initiative on therapeutic science and strong links with CRUK and with national labs and industry leaders in drug development. The interdisciplinary team involved in this IRC includes groups from five universities with expertise ranging from materials synthesis and characterisation, through device engineering and manufacturing, to pharmacology and cancer, and will deliver scientific breakthroughs that extend beyond the field of targeted drug delivery. Economic and societal impacts will be delivered and measured through a joined-up approach to market analysis, industry feedback and embedded anticipation of risks to translation. Engagement of end-users and stakeholders, which will begin as early as the preparation of the second-round proposal, will play a critical role in steering the IRC throughout its lifetime.