SUPPLEMENTARY INFORMATION Typical measurement sequenceThe nucleation rates (J cm −3 s −1 ) are measured under neutral (J n ), galactic cosmic ray (J gcr ) or charged pion beam (J ch ) conditions. For J gcr a beam stopper blocks the pions and the chamber is irradiated by GCRs together with a small parasitic component of penetrating beam muons, whereas, for J ch , the beam stopper is opened and the pion beam is normally set to a time-averaged rate of (5 − 6) · 10 4 s −1 . Neutral nucleation rates are measured

Realization of the immense potential of nanomaterials for biomedical applications will require a thorough understanding of how they interact with cells, tissues, and organs. There is evidence that, depending on their physicochemical properties and subsequent interactions, nanomaterials are indeed taken up by cells. However, the subsequent release and/or intracellular degradation of the materials, transfer to other cells, and/or translocation across tissue barriers are still poorly understood. The involvement of these cellular clearance mechanisms strongly influences the long-term fate of used nanomaterials, especially if one also considers repeated exposure. Several nanomaterials, such as liposomes and iron oxide, gold, or silica nanoparticles, are already approved by the American Food and Drug Administration for clinical trials; however, there is still a huge gap of knowledge concerning their fate in the body. Herein, clinically relevant nanomaterials, their possible modes of exposure, as well as the biological barriers they must overcome to be effective are reviewed. Furthermore, the biodistribution and kinetics of nanomaterials and their modes of clearance are discussed, knowledge of the long-term fates of a selection of nanomaterials is summarized, and the critical points that must be considered for future research are addressed.

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