Two different protein corona formation modes on Soluplus® nanomicelles.

Soluplus® nanomicelles have been widely reported in biomedical field for their excellent drug loading capacity and solubility enhancement ability. However, when administrated in vivo, the protein corona will be formed on Soluplus® nanomicelles, significantly affecting their drug delivery performance. Up to now, few studies examined the protein corona formation process and its impact factors of Soluplus® nanomicelles. The multiple proteins in biofluids may form protein corona in different modes due to their diversified properties. In this study, Bovine serum albumin (BSA), Lysozyme (Lyso) and Bovine hemoglobin (BHb) were chosen as model proteins to investigate the protein corona formation process of Soluplus® nanomicelles. By analyzing the polarity of the protein amino acid residues distributing microenvironments, the results showed that there were two different protein corona formation modes, i.e., surface adsorption and insertion, which were determined by the hydrophilicity of proteins. The hydrophobic BHb followed the insertion mode while hydrophilic BSA and Lyso followed the surface adsorption mode. Ultimately, upon protein corona formation, the size and surface chemistry of nanomicelles was significantly affected. We believe this study will provide a new research paradigm to the design and application of Soluplus® nanomicelles.