Protein corona: Friend or foe? Co-opting serum proteins for nanoparticle delivery.

[Display omitted] • Protein corona interferes with the intended function of nanoparticles, such as target-specific interactions. • Previous efforts have focused on avoiding protein corona formation or overriding the effect of the protein corona. • Specific proteins in the blood, such as albumin or apolipoproteins, can enhance nanoparticle delivery to particular organs. • To exploit the functions of protein corona, nanoparticles are functionalized with the proteins or designed to attract them. • Remaining challenges include interpatient variability in serum proteins and poor understanding of non-protein corona. For systemically delivered nanoparticles to reach target tissues, they must first circulate long enough to reach the target and extravasate there. A challenge is that the particles end up engaging with serum proteins and undergo immune cell recognition and premature clearance. The serum protein binding, also known as protein corona formation, is difficult to prevent, even with artificial protection via "stealth" coating. Protein corona may be problematic as it can interfere with the interaction of targeting ligands with tissue-specific receptors and abrogate the so-called active targeting process, hence, the efficiency of drug delivery. However, recent studies show that serum protein binding to circulating nanoparticles may be actively exploited to enhance their downstream delivery. This review summarizes known issues of protein corona and traditional strategies to control the corona, such as avoiding or overriding its formation, as well as emerging efforts to enhance drug delivery to target organs via nanoparticles. It concludes with a discussion of prevailing challenges in exploiting protein corona for nanoparticle development. [ABSTRACT FROM AUTHOR]