Metal-organic frameworks as a modular platform for advanced drug delivery

纳米颗粒给药系统（DDS）因其极大地提高许多治疗药物的安全性和有效性的潜力而受到越来越多的关注。这些系统解决的关键挑战包括不溶性、稳定性差或具有显著脱靶效应的活性药物成分（API）。这些对于癌症治疗和新型基因治疗尤其重要，癌症治疗通常具有高毒性，而新型基因治疗不稳定，无法跨越生物屏障。通过将API分子包封或以其他方式保持在纳米载体内，治疗剂可以被赋予广泛的有益的药代动力学性质，包括缓慢和靶向释放。然而，当前的技术提供了非互补和高度碎片化的工具箱，其中个别方法仅能够用潜在API的子集来解决这些挑战的子集。结果是，运营商需要为每个应用进行艰苦的优化和表征。该领域将通过“即插即用”系统大大简化，在该系统中，新的API -无论其大小或化学性质如何-都可以装入通用载体，然后根据其功能进行修改。该项目将开发基于金属有机框架（MOF）的新型DDS，金属有机框架是一类具有非常广泛功能的材料，并采用模块化方法进行车辆设计。它们几乎可以接受任何API，并根据需要使用行业标准技术进行修改。这意味着，一种MOF载体，一旦被证明与一种特定的药物，可能会与一种新药表现相似;而一种表面修饰--一旦其影响被表征--可能会在应用于一种新载体时表现相似。因此，MOFs可能为载体设计提供一种“模块化工具箱”方法，并可能是迄今为止最接近真正的即插即用系统的技术。Vector Bioscience与Medicines Discovery Catapult一起，正在努力加速这项技术向临床的过渡。这个为期2年的项目将试图证明该平台在传统小分子治疗、抗体靶向递送和新型siRNA基因疗法递送方面的功能。它将针对临床相关的_体内_里程碑，涵盖该技术的有效性，生物相容性和药代动力学。在此过程中，它将验证和降低制药行业的技术风险，使合作得以构建，并在项目完成后继续开发平台。这个项目的重点是胰腺癌。然而，该平台具有广泛的适用性，将在项目后探索邻近地区。

Nanoparticle drug delivery systems (DDS) are seeing growing attention for their potential to drastically improve the safety and efficacy of many therapeutics. Key challenges these systems address include active pharmaceutical ingredients (APIs) that are insoluble, have poor stability or have significant off-target effects. These are particularly important for cancer therapies, which are often highly toxic, and novel gene therapies, which are unstable and cannot cross biological barriers. By encapsulating or otherwise holding API molecules within a nanocarrier, therapeutics can be given a wide range of beneficial pharmacokinetic properties, including slow and targeted release.Current technologies, however, provide a non-complementary and highly fragmented toolbox, with individual approaches that are only able to address a subset of these challenges with a subset of potential APIs. The result is that carriers require painstaking optimisation and characterisation for each application. The field would be considerably streamlined by a "plug-and-play" system, in which a new API -- regardless of its size or chemistry -- could be loaded into a universal carrier, which is then altered to suit its function.This project will develop a novel DDS based on metal-organic frameworks (MOFs), a class of materials with exceptionally broad functionality and a modular approach to vehicle design. They can accept virtually any API and be modified as required using industry-standard techniques. This means that a MOF carrier, once proven with a particular drug, might be expected to behave similarly with a new drug; and a surface modification -- once its impact has been characterised -- might be expected to behave similarly when applied to a new carrier. MOFs may therefore offer a "modular toolbox" approach to carrier design and potentially the closest technology yet to a true plug-and-play system.Vector Bioscience, together with the Medicines Discovery Catapult, is working to accelerate the transition of this technology to the clinic. This 2-year project will seek to demonstrate the functionality of the platform across conventional small-molecule therapeutics, antibody-targeted delivery, and delivery of novel siRNA gene therapies. It will target clinically relevant _in vivo_ milestones covering the technology's efficacy, biocompatibility, and pharmacokinetics. In doing so, it will validate and de-risk the technology to the pharmaceutical industry, enabling collaborations to be structured and the development of the platform to continue once the project is complete. The focus of this project is pancreatic cancer. However, the platform has broad applicability and adjacent areas will be explored post-project.