The interaction between nanoparticles-protein corona complex and cells and its toxic effect on cells

Once nanoparticles (NPs) contact with the biological fluids, the proteins immediately adsorb onto their surface, forming a layer called protein corona (PC), which bestows the biological identity on NPs. Importantly, the NPs-PC complex is the true identity of NPs in physiological environment. Based on the affinity and the binding and dissociation rate, PC is classified into soft protein corona, hard protein corona, and interfacial protein corona. Especially, the hard PC, a protein layer relatively stable and closer to their surface, plays particularly important role in the biological effects of the complex. However, the abundant corona proteins rarely correspond to the most abundant proteins found in biological fluids. The composition profile, formation and conformational change of PC can be affected by many factors. Here, the influence factors, not only the nature of NPs, but also surface chemistry and biological medium, are discussed. Likewise, the formed PC influences the interaction between NPs and cells, and the associated subsequent cellular uptake and cytotoxicity. The uncontrolled PC formation may induce undesirable and sometimes opposite results: increasing or inhibiting cellular uptake, hindering active targeting or contributing to passive targeting, mitigating or aggravating cytotoxicity, and stimulating or mitigating the immune response. In the present review, we discuss these aspects and hope to provide a valuable reference for controlling protein adsorption, predicting their behavior in vivo experiments and designing lower toxicity and enhanced targeting nanomedical materials for nanomedicine.