In situ detection of protein corona on single particle by rotational diffusivity

Since the formation of protein corona inevitably leads to an increase in the particle size, it is important to develop technologies enabling in situ monitoring of the size change of nanoparticles. Traditional diffusion-based methods for particle size measurement focused on the translational diffusion coefficient; however, the detection sensitivity can be improved by determining the rotational diffusion coefficient, which has a cubic dependence on the particle radius. Here, using an optically anisotropic gold nanorod as the rotational probe and using high-speed dark-field microscopy, we can extract the rotational diffusion coefficient of a single nanorod and monitor the size change induced by the formation of protein corona in situ in real time. We successfully determined the thermodynamic parameters for the interactions between AuNRs with BSA and fibrinogen, and also studied corona formation in complex media and with AuNRs with different surface chemistry. This work would provide new avenues for the study of interactions between nanomedicines and proteins.