A KEY TO THE RATIONAL DESIGN OF EXTRACELLULAR VESICLES-MIMICKING NANOPARTICLES

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The MIMIC-KEY project proposes to study extracellular vesicles (EVs) to understand their targeting behavior and cargo delivery in natural systems. Such comprehension will be used to build up new artificial materials that have the same targeting capabilities, but are much more scalable and mono disperse of the natural EVs. The MIMICK-KEY concept is to learn from tumor-derived EVs and from their ability to recognize and target tissue-specific features during metastasis. Thus, cancer is not the disease to treat but a source of inspiration to build artificial nanomaterials that mimic the EVs and enable them to fight other clinically unmet diseases, specifically metabolic bone disorders. To achieve this ambitious goal, two main steps are required: 1) Deep understanding of the key molecular features enabling EVs for specific targeting and cargo release to the recipient cells. This will be achieved thanks to a synergistic combination of groundbreaking and multidisciplinary approaches (correlative flow cytometry and super-resolution imaging, biological proteomic profiling, multiscale simulations) of an excellent partnership throughout Europe. 2) Synthetically build artificial EV-mimics towards a clinically relevant formulation. The new EV-mimics will be core-shell structures coated by a mobile, dynamic lipid bilayer shell incorporating key-functional proteins for targeting, enabling a novel enzyme-based therapy against metabolic disease that will be tested in vitro and in vivo. The breakthrough idea of artificial EV-mimics, using only essential building blocks and amplifying their therapeutic functions, will overcome the current limitations of natural EVs and represent a challenge at the frontiers of research. MIMICK-KEY is a high-risk proposal that if successful can lead to a completely new way to conceive bio-inspired mimetic nanoparticles and their functions, impacting on a plethora of applications, primarily the pharmaceutical industry and theranostic nanomedicine field.