白蛋白纳米粒子（NP）和聚乙二醇化脂质体由于其独特的理化性质而作为治疗药物载体引起了极大的兴趣。这些独特的性质也对生物环境中这些纳米粒子周围形成的蛋白质冠的组成和结构产生显着影响。在此，通过体外和模拟研究同时评估了白蛋白纳米颗粒和脂质体上的蛋白冠形成。两种类型的纳米粒子在被引入胎牛血清后，其尺寸随着带负电荷的界面的增加而增加。通过凝胶电泳和无标记定量蛋白质组学来鉴定硬冠上募集的蛋白质，发现白蛋白纳米粒子中的蛋白质比脂质体中的蛋白质少，这与等温滴定量热法一致。两种纳米颗粒的细胞摄取效率在不同的血清浓度下存在显着差异，通过将抗癌化合物负载到白蛋白纳米颗粒中进一步检查了这一点。与脂质体相比，硬蛋白冠的存在增加了白蛋白纳米颗粒的细胞摄取。在我们的模拟研究中，膜中存在的特定受体被白蛋白-载脂蛋白 E 复合物极大地吸引。总体而言，这项研究不仅评估了白蛋白纳米颗粒上蛋白冠的形成，而且在基于白蛋白和脂质体的治疗系统方面取得了有希望的进展。

Albumin nanoparticles (NPs) and PEGylated liposomes have garnered tremendous interest as therapeutic drug carriers due to their unique physicochemical properties. These unique properties also have significant effects on the composition and structure of the protein corona formed around these NPs in a biological environment. Herein, protein corona formation on albumin NPs and liposomes was simultaneously evaluated through in vitro and simulation studies. The sizes of both types of NPs increased with more negatively charged interfaces upon being introduced into fetal bovine serum. Gel electrophoresis and label-free quantitative proteomics were performed to identify proteins recruited to the hard corona, and fewer proteins were found in albumin NPs than in liposomes, which is in accordance with isothermal titration calorimetry. The cellular uptake efficiency of the two NPs significantly differed in different serum concentrations, which was further scrutinized by loading an anticancer compound into albumin NPs. The presence of the hard protein corona increased the cellular uptake of albumin NPs in comparison with liposomes. In our simulation study, a specific receptor present in the membrane was greatly attracted to the albumin-apolipoprotein E complex. Overall, this study not only evaluated protein corona formation on albumin NPs, but also made promising advancements toward albumin- and liposome-based therapeutic systems.