The Nanostructured Secretome
The term secretome, which traditionally refers only to single proteins, may be expanded to also include the great variety of nanoparticles secreted by cells (secNPs) into the extracellular space, which ranges from high-density lipoproteins of few nm to extracellular vesicles and fat globules of hundreds of nm. Widening the definition is urged by the ever-increasing understanding of secNP role as regulators/mediators of key physiological and pathological processes, which also puts them in the running as breakthrough cell-free therapeutics and diagnostics. “made by cells for cells”, secNPs are envisioned as a sweeping paradigm-shift in nanomedicine, promising to overcome the limitations of synthetic nanoparticles by unsurpassed circulation and targeting abilities, precision and sustainability. On a longer/wider perspective, advanced manipulation would possibly make secNPs available as building blocks for future “biogenic” nanotechnology. However, current knowledge is fragmented and sectorial (the majority of the studies being focused on a specific biological and/or medical aspect of a given secNP class or subclass), understanding of the nanoscale and interfacial properties limited and development of bioprocesses and regulatory initiatives in the early days. We believe new multidisciplinary competencies and synergistic efforts need to be attracted and augmented to step forward. This review will contribute to the effort by (the first attempt to) setting secNPs into a unique concise framework.