State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.
J Nanobiotechnology. 2021 Dec 23;19(1):445. doi: 10.1186/s12951-021-01140-8.
Phosphomolybdate-based nanoparticles (PMo-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-based NPs (CDS-PMo@PVP(x = 0 ~ 1) NPs) capping diverse content of zwitterionic polymer poly (N-vinylpyrrolidone) (PVP) to regulate the protein corona formation on PMo-based NPs. The fluorescence quenching data indicate that the introduction of PVP effectively reduces the number of binding sites of proteins on PMo-based NPs. Molecular docking simulations results show that the contact surface area and binding energy of proteins to CDS-PMo@PVP NPs are smaller than the CDS-PMo@PVP 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@PVP(x = 0 ~ 1) NPs. The number of plasma protein groups adsorption on CDS-PMo@PVP NPs, compared to CDS-PMo@PVP NPs, decreases from 372 to 271. In addition, 76 differentially adsorption proteins are identified between CDS-PMo@PVP and CDS-PMo@PVP NPs, in which apolipoprotein is up-regulated in CDS-PMo@PVP 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-based NPs is a promising strategy to improve the anti-biofouling property for PMo-based nanodrug design.
基于磷钼酸盐的纳米粒子（PMo 基 NPs）已广泛应用于纳米医学。然而，当与生物流体接触时，蛋白质会迅速吸附在 NPs 表面形成蛋白质冠，从而引发调理作用，并促进巨噬细胞摄取 NPs 迅速清除。在此，我们介绍了一组结构同源的基于磷钼酸盐的 NPs（CDS-PMo@PVP(x=01) NPs），其表面接枝了不同含量的两性离子聚合物聚（N-乙烯基吡咯烷酮）（PVP），以调节基于磷钼酸盐的 NPs 上蛋白质冠的形成。荧光猝灭数据表明，PVP 的引入有效地减少了蛋白质与基于磷钼酸盐的 NPs 结合的位点数量。分子对接模拟结果表明，蛋白质与 CDS-PMo@PVP NPs 的接触表面积和结合能小于 CDS-PMo@PVP NPs。进一步采用液相色谱-串联质谱（LC-MS/MS）分析和定量人血浆冠形成物在 CDS-PMo@PVP(x=01) NPs 上的组成。与 CDS-PMo@PVP NPs 相比，CDS-PMo@PVP NPs 上吸附的血浆蛋白组数量从 372 个减少到 271 个。此外，在 CDS-PMo@PVP 和 CDS-PMo@PVP NPs 之间鉴定出 76 个差异吸附蛋白，其中载脂蛋白在 CDS-PMo@PVP NPs 中上调。提出将载脂蛋白吸附到 NPs 上具有非生理活性，并增强 NPs 的循环时间。我们的研究结果表明，在 PMo 基 NPs 上接枝 PVP 是提高 PMo 基纳米药物设计抗生物污染性能的一种有前途的策略。
