Fast and Dynamic Mapping of the Protein Corona on Nanoparticle Surfaces by Photocatalytic Proximity Labeling

Abstract Protein corona broadly affects the delivery of nanomedicines in vivo. Although it has been widely studied by multiple strategies like centrifugal sedimentation, the rapidly forming mechanism and the dynamic structure of the protein corona at the seconds level remains challenging. Here, a photocatalytic proximity labeling technology in nanoparticles (nano‐PPL) is developed. By fabricating a “core‐shell” nanoparticle co‐loaded with chlorin e6 catalyst and biotin‐phenol probe, nano‐PPL technology is validated for the rapid and precise labeling of corona proteins in situ. Nano‐PPL significantly improves the temporal resolution of nano‐protein interactions to 5 s duration compared with the classical centrifugation method (>30 s duration). Furthermore, nano‐PPL achieves the fast and dynamic mapping of the protein corona on anionic and cationic nanoparticles, respectively. Finally, nano‐PPL is deployed to verify the effect of the rapidly formed protein corona on the initial interaction of nanoparticles with cells. These findings highlight a significant methodological advance toward nano‐protein interactions in the delivery of nanomedicines in vivo.