Surface chemistry and serum type both determine the nanoparticle–protein corona

The protein corona that forms around nanoparticles in vivo is a critical factor that affects their physiological response. The potential to manipulate nanoparticle characteristics such that either proteins advantageous for delivery are recruited and/or detrimental proteins are avoided offers exciting possibilities for improving drug delivery. In this work, we used nanoliquid chromatography tandem mass spectrometry to characterize the corona of five lipid formulations after incubation in mouse and human plasma with the hope of providing data that may contribute to a better understanding of the role played by both the nanoparticle properties and the physiological environment in recruiting specific proteins to the corona. Notably, we showed that minor changes in the lipid composition might critically affect the protein corona composition demonstrating that the surface chemistry and arrangement of lipid functional groups are key players that regulate the liposome–protein interactions. Notably, we provided evidence that the protein corona that forms around liposomes is strongly affected by the physiological environment, i.e., the serum type. These results are likely to suggest that the translation of novel pharmaceutical formulations from animal models to the clinic must be evaluated on a case-by-case basis.