How does “Protein Corona” Affect the In vivo Efficiency of Polymeric Nanoparticles? State of Art

Nanomedicine is increasingly considered as one of the most promising ways to overcome the limits of traditional medicine and conventional pharmaceutical formulations. In particular, polymeric nanoparticles (NPs) represent one of the most important tools in the nanomedicine field due to their potential in a wide range of biomedical applications such as imaging, drug targeting and drug delivery. However, their application is strongly hampered by limited knowledge and control of their interactions with complex biological systems. In biological environments, NPs are enshrouded by a layer of biomolecules, predominantly proteins, which tend to associate with NPs, forming a new surface named 'protein corona' (PC). Thus, the resulting nano-structure is a new entity, defined as PC-NP complex, featured by new characteristics, different from the original features of the bare NPs. In this chapter, starting from the definition of PC, we critically discuss the physico-chemical properties of polymeric NPs (e.g., size, shape, composition, surface functional groups, surface charge, hydrophilicity/hydrophobicity) and the environmental biological parameters (blood concentration, plasma gradient, temperature) affecting PC formation and composition. We further discuss how the new “entity” generated by the interactions between NPs and proteins in vivo mediates the ability of all the nanosystems to circulate, biodistribute and selectively release the drugs to the target site. We conclude by highlighting the gaps in the knowledge of the PC in relation to polymeric NPs and by discussing the main issues to be addressed and investigated in order to speed up the translatability of NPs into clinical protocols.