Unmasking CSF protein corona: Effect on targeting capacity of nanoparticles

Among biological fluids, cerebrospinal fluid (CSF) not only protects and support brain, but also plays a pivotal role in intracerebral interaction of various nano-drug carriers. However, it is still uncertain how protein corona from CSF affects the targeting capability of functionalized nanoparticles (NPs). So, two types of polystyrene NPs, including PEGylated polystyrene NPs (PN) and transferrin (Tf)-modified PN (PT), were used to obtain protein corona-coated NPs, by incubating with CSF in vivo and in vitro. Strikingly, both the corona-coated NPs recovered in vivo and in vitro completely lost their active targeting characteristics towards bEnd.3 and C6 cells. Charge-, clathrin- and energy-mediated endocytosis contributed to the improved uptake efficiency of PT, whereas this enhancement in uptake of PT was disappeared after the formation of CSF protein corona. Moreover, serum albumin, which were found both in vivo and in vitro CSF corona, could mediate and facilitate the internalization of corona-coated NPs. Overall, these results have distinctly confirmed that the formation of CSF protein corona could cause the loss of active targeting specificity by shielding the targeting groups on the surface of polystyrene NPs and alter their cellular uptake by other non-specific internalization pathways.