Plasma protein adsorption and biological identity of systemically administered nanoparticles

Although a variety of nanoparticles (NPs) have been used for drug delivery applications, their surfaces are immediately covered by plasma protein corona upon systemic administration. As a result, the adsorbed proteins create a unique biological identity of the NPs that lead to unpredictable performance. The protein corona on NPs could also impede active targeting, induce off-target effects, trigger particle clearance and even provoke toxicity. This article reviews the fundamentals of NP-plasma protein interaction, the consequences of the interactions, and provides insights into the correlations of protein corona with biodistribution and cellular delivery. We hope that this review will trigger additional questions and possible solutions that lead to more favorable developments in NP-based targeted delivery systems.