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年中翻了一番，但难以治疗的癌症的存活率低于14%。为了对抗这些癌症，需要靶向多种途径（免疫/炎症、新血管生成、细胞复制），这需要多模式递送方法，其不仅增加到达靶部位的治疗剂的量，而且增加其范围。该研究中心将通过开发（i）基于金属有机框架和有机笼并显示出显著增加的有效载荷能力的递送载体，以及（ii）基于凝胶和电泳泵并增强药物穿透例如血脑屏障的可植入/可注射递送平台来应对这一挑战。通过结合这两种方法，我们将实现到达肿瘤部位的药物数量和范围的阶跃变化。两个横向的翻译活动，关于材料输送和增材制造以及验证，将考虑从输送系统的概念到其临床应用的整个链条，从而为靶向药物输送问题提供整体方法。拟议的研究计划建立在机构层面的治疗科学倡议以及与CRUK以及国家实验室和药物开发行业领导者的密切联系基础上。参与该IRC的跨学科团队包括来自五所大学的团队，他们的专业知识范围从材料合成和表征，到设备工程和制造，再到药理学和癌症，并将实现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、行业反馈和嵌入式翻译风险预测的联合方法来实现和衡量。最终用户和利益攸关方的参与早在编写第二轮提案时就将开始，这将在指导因诺琴蒂研究中心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.