Small extracellular vesicles contain metals and transfer metal intercellularly

Cells have developed a highly regulated system for the uptake, transport, utilization, storage, and export of metals, ensuring the maintenance of cellular homeostasis. Small extracellular vesicles (sEVs) function as a mechanism through which a cell can export its cargo and transfer it to recipient cells. However, in contrast to the other molecular cargo associated with sEVs, the metal content of sEVs is not well characterized. To address this gap in knowledge, we measured the levels of nine essential metals (copper, iron, zinc, manganese, magnesium, potassium, calcium, chromium, cobalt) and six non-essential metals (nickel, rubidium, titanium, aluminium, lithium, lead) in sEVs originating from multiple in vitro and ex vivo sources. Our findings reveal that, beyond containing redox-active essential metals and those involved in redox reactions, sEVs also exhibit the capability to export and transfer non-physiological, potentially toxic metals.