Quantitative Protein Corona Composition and Dynamics on Carbon Nanotubes in Biological Environments

Abstract When nanoparticles enter biological environments, proteins adsorb to form the “protein corona” which alters nanoparticle biodistribution and toxicity. Herein, we measure protein corona formation on DNA‐functionalized single‐walled carbon nanotubes (ssDNA‐SWCNTs), a nanoparticle used widely for sensing and delivery, in blood plasma and cerebrospinal fluid. We characterize corona composition by mass spectrometry, revealing high‐abundance corona proteins involved in lipid binding, complement activation, and coagulation. We investigate roles of electrostatic and entropic interactions driving selective corona formation. Lastly, we study real‐time protein binding on ssDNA‐SWCNTs, obtaining agreement between enriched proteins binding strongly and depleted proteins binding marginally, while highlighting cooperative adsorption mechanisms. Knowledge of protein corona composition, formation mechanisms, and dynamics informs nanoparticle translation from in vitro design to in vivo application.