Mapping the heterogeneity of protein corona by ex vivo magnetic levitation

In the past decade, we witnessed limited success in the clinical translation of therapeutic nanoparticles (NPs). One of the main reasons for this limited success is our poor understanding of the biological identity of NPs. Herein, we report magnetic levitation (MagLev) as a complementary analytical tool to investigate the homogeneity of the created protein corona (PC) coated NPs through an ex vivo model. Our results demonstrate that the MagLev system not only has the capacity to separate corona coated NPs, but also enables us to study the homogeneity/heterogeneity of the PC. Our findings suggest that current ex vivo isolation methods cause a heterogeneous coverage of PC profiles at the surface of NPs. The MagLev technique, therefore, would be instrumental in identifying and separating fully PC coated NPs which, in turn, enables us to achieve more accurate information on protein corona composition. Ultimately, we believe that the MagLev technique can be used for the fast screening of the homogeneity of corona coated NPs before quantitative analysis of the corona profile/composition, hence definitely improving our fundamental understanding of nano-bio interfaces.