Nanoparticles (NPs) can be used to design for nanomedicines with different chemical surface properties owing to their size advantages and the capacity of specific delivery to targeted sites in organisms. The discovery of the presence of protein corona (PC) has changed our classical view of NPs, stimulating researchers to investigate the in vivo fate of NPs as they enter biological systems. Both NPs and PC have their specificity but complement each other, so they should be considered as a whole. The formation and characterization of NP-PC complexes provide new insights into the design, functionalization, and application of nanocarriers. Based on progress of recent researches, we reviewed the formation, characterization, and composition of the PC, and introduced those critical factors influencing PC, simultaneously expound the effect of PC on the biological function of NPs. Especially we put forward the opportunities and challenges when NP-PC as a novel nano-drug carrier for targeted applications. Furthermore, we discussed the pros versus cons of the PC, as well as how to make better PC in the future application of NPs.

When nanoparticles enter the physiological environment, dense hard corona and loose soft corona are formed quickly. Adsorption of some proteins, such as immunoglobulin and complement factor, is conducive to the recognition and phagocytosis of phagocytes, but also causes other innate immune reactions or immunotoxicity of some organs. Protein coronas and nanoparticles interact and influence each other. Protein corona-nanoparticle complexes provides a new idea for the design of nanoparticles. On the one hand, some special nanomaterials or functional groups and targeted molecules are encouraged to break through the barrier of protein corona. On the other hand, protein coronas provide a new identity and application potential for nanoparticles.