Towards a Mechanistic Understanding of Nanoparticle Interactions with Exosome Secretion

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In recent decades, considerable progress has been made in bio-nano research towards a growing understanding of the interaction mechanisms between nanoparticles (NPs) and living systems. Yet, the impact that cell-internalised NPs have on exosome secretion remains largely unknown. Exosomes are ubiquitous cell-released vesicles seemingly involved in numerous biological processes, including regulation of cell-cell communication and disease progression. This enigmatic functional complexity is under the spotlight of a large scientific community in the fields of chemistry, biology and nanomedicine. Only recently, it has been reported that in vitro cellular uptake of platinum and iron oxide NP clusters (~ 100 nm in size) significantly increases the release of exosomes and alters their composition. However, it is unclear whether this evidence reflects a general behaviour or depends on the design of the NPs. A strong need thus arises to explore the mechanistic details of this interaction. Inspired by this challenge, NanoEXOS aims to develop a novel framework to obtain a better and more general understanding of how engineered NPs interfere with the regulatory processes of exosome formation and release. NP-cell studies will be undertaken in vitro to focus on the effects that NPs have on cell-specific exosome samples. Importantly, NanoEXOS will systematically investigate how this interaction depends on the properties of NPs (e.g. well-defined size, shape, surface modification), their biomolecular interactions and their cellular entry mechanism. Overall, NanoEXOS will contribute to expanding our knowledge of how exogenous NPs are processed by living systems. A thorough comprehension of how NPs access and alter key cellular machineries, such as exosome secretion, plays a pivotal role in the biological evaluation of these nanomaterials. This research question is crucial to establish safe and robust biological control over advanced NP-assisted diagnostic and therapeutic strategies.