This thesis aims to comprehensively investigate the intricate interactions between NPs of different surface charges and plasma proteins, to understand the process of PC formation and its influence on the behavior of these NPs. The primary goal was to discern the effect of NP surface charge on the composition of the PC and establish a correlation between this composition and key proteins observed in vivo. Additionally, in vitro studies were designed to explore the in vivo-in vitro correlation of protein adsorption, thereby exploring the potential to simplify further protein corona investigations.