Poly ( N -vinylpyrrolidone) modification mitigates plasma protein corona formation on phosphomolybdate-based nanoparticles

Phosphomolybdate-based nanoparticles (PMo 12 -based NPs) have been commonly applied in nanomedicine. However, upon contact with biofluids, proteins are quickly adsorbed onto the NPs surface to form a protein corona, which induces the opsonization and facilitates the rapid clearance of the NPs by macrophage uptake. Herein, we introduce a family of structurally homologous PMo 12 -based NPs (CDS-PMo 12 @PVP x (x = 0 ~ 1) NPs) capping diverse content of zwitterionic polymer poly ( N -vinylpyrrolidone) (PVP) to regulate the protein corona formation on PMo 12 -based NPs. The fluorescence quenching data indicate that the introduction of PVP effectively reduces the number of binding sites of proteins on PMo 12 -based NPs. Molecular docking simulations results show that the contact surface area and binding energy of proteins to CDS-PMo 12 @PVP 1 NPs are smaller than the CDS-PMo 12 @PVP 0 NPs. The liquid chromatography-tandem mass spectrometry (LC–MS/MS) is further applied to analyze and quantify the compositions of the human plasma corona formation on CDS-PMo 12 @PVP x (x = 0 ~ 1) NPs. The number of plasma protein groups adsorption on CDS-PMo 12 @PVP 1 NPs, compared to CDS-PMo 12 @PVP 0 NPs, decreases from 372 to 271. In addition, 76 differentially adsorption proteins are identified between CDS-PMo 12 @PVP 0 and CDS-PMo 12 @PVP 1 NPs, in which apolipoprotein is up-regulated in CDS-PMo 12 @PVP 1 NPs. The apolipoprotein adsorption onto the NPs is proposed to have dysoponic activity and enhance the circulation time of NPs. Our findings demonstrate that PVP grafting on PMo 12 -based NPs is a promising strategy to improve the anti-biofouling property for PMo 12 -based nanodrug design. Graphical Abstract