Impact of Surface-Engineered ZnO Nanoparticles on Protein Corona Configuration and Their Interactions With Biological...

In biological system, the interaction between nanoparticles (NPs) and serum biomolecules results in the formation of a dynamic corona of different affinities. The formed corona enriched with opsonin protein is recognized by macrophages and immune effector cells, resulting in rapid clearance with induced toxicity. Hence, to reduce corona genesis, surface-engineered ZnO (c-ZnO) NPs were in situ synthesized using a polyacrylamide-grafted guar gum (PAm-g-GG) polymer that provided surface neutrality to the NPs. Furthermore, we studied the characteristics of the corona formed onto uncapped anionic ZnO (bared ZnO [b-ZnO]) NPs and c-ZnO NPs by serum incubation. The result shows that b-ZnO NPs were wrapped with a high amount of serum proteins, particularly opsonin (IgG and complement), compared with c-ZnO NPs. These corona findings helped us substantially in interpretation of in vivo biokinetics studies. The in vivo study was accomplished by oral administration of NPs to Swiss mice at doses of 300 and 2000 mg/kg body weight. The studies performed on the cellular uptake, intracellular particle distribution, cytotoxicity, and pharmacokinetics of NPs indicated that b-ZnO NPs experienced higher immune cell recognition, hepatic inflammation, and resultant rapid clearance from the system, unlike c-ZnO NPs. Thus, capping of NPs by a neutral polymer has provided limited binding sites for undesired proteins around NPs, which limits immune system activation.