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

纳米颗粒给药系统（DDS）正因其极大地提高许多治疗方法的安全性和有效性的潜力而受到越来越多的关注。这些系统解决的主要挑战包括不溶性、稳定性差或具有显著脱靶效应的活性药物成分（api）。这对癌症治疗和新基因治疗尤其重要，因为癌症治疗通常具有高毒性，而新基因治疗不稳定，不能跨越生物屏障。通过将原料药分子包封或以其他方式保存在纳米载体中，治疗剂可以获得广泛的有益药代动力学特性，包括缓慢和靶向释放。然而，当前的技术提供了一个非互补且高度分散的工具箱，单个方法只能用潜在api的子集来解决这些挑战的子集。结果是，载体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，无论新API的大小或化学成分如何，都可以加载到通用载体中，然后根据其功能进行修改。该项目将开发一种基于金属有机框架（mof）的新型DDS，这是一种具有非常广泛功能的材料，可用于车辆设计的模块化方法。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MOF载体一旦被证明具有特定药物的作用，可能会对新药产生类似的作用；表面改性——一旦它的影响被表征出来——可能会在应用于新的载体时表现出类似的行为。因此，mof可以为载体设计提供一种“模块化工具箱”方法，并且可能是最接近于真正的即插即用系统的技术。Vector Bioscience与药物发现弹射器（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年的项目将寻求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，涵盖该技术的功效、生物相容性和药代动力学。在此过程中，它将验证制药行业的技术并降低风险，使合作能够结构化，平台的开发能够在项目完成后继续进行。这个项目的重点是胰腺癌。然而，该平台具有广泛的适用性，项目后将对邻近地区进行探索。

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.