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

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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.