What the biological cell, organ, or barrier actually sees when interacting with a nanoparticle dispersed in a biological medium likely matters more than the bare material properties of the particle itself. Typically the bare surface of the particle is covered by several biomolecules, including a select group of proteins drawn from the biological medium. Here, we apply several different methodologies, in a time-resolved manner, to follow the lifetime of such biomolecular coronas both in situ and isolated from the excess plasma. We find that such particle-biomolecule complexes can be physically isolated from the surrounding medium and studied in some detail, without altering their structure. For several nanomaterial types, we find that blood plasma-derived coronas are sufficiently long-lived that they, rather than the nanomaterial surface, are likely to be what the cell sees. From fundamental science to regulatory safety, current efforts to classify the biological impacts of nanomaterials (currently according to bare material type and bare surface properties) may be assisted by the methodology and understanding reported here.
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