Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, College of Food Science, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing 400715, China.
ACS Appl Mater Interfaces. 2021 Dec 8;13(48):58238-58251. doi: 10.1021/acsami.1c19824. Epub 2021 Nov 19.
Much has been learned about the protein coronae and their biological implications within the context of nanomedicine and nanotoxicology. However, no data is available about the protein coronae associated with nanoparticles undergoing spontaneous surface-energy minimization, a common phenomenon during the synthesis and shelf life of nanomaterials. Accordingly, here we employed gold nanoparticles (AuNPs) possessing the three initial states of spiky, midspiky, and spherical shapes and determined their acquisition of human plasma protein coronae with label-free mass spectrometry. The AuNPs collected coronal proteins that were different in abundance, physicochemical parameters, and interactive biological network. The size and structure of the coronal proteins matched the morphology of the AuNPs, where small globular proteins and large fibrillar proteins were enriched on spiky AuNPs, while large proteins were abundant on spherical AuNPs. Furthermore, the AuNPs induced endothelial leakiness to different degrees, which was partially negated by their protein coronae as revealed by confocal fluorescence microscopy, and transwell assays, and signaling pathway assays. This study has filled a knowledge void concerning the dynamic protein corona of nanoparticles possessing an evolving morphology and shed light on their implication for future nanomedicine harnessing the paracellular pathway.
在纳米医学和纳米毒理学领域，人们已经对蛋白冠及其生物学意义有了很多了解。然而，对于在纳米材料合成和储存过程中常见的自发表面能最小化过程中与纳米颗粒相关的蛋白冠，目前还没有数据。因此，在这里，我们使用具有刺状、中刺状和球形三种初始状态的金纳米颗粒（AuNPs），并采用无标记质谱法确定了它们与人血浆蛋白冠的结合情况。AuNPs 收集到的冠蛋白在丰度、物理化学参数和相互作用的生物网络方面存在差异。冠蛋白的大小和结构与 AuNPs 的形态相匹配，其中小的球形蛋白和大的纤维状蛋白在刺状 AuNPs 上富集，而大的蛋白在球形 AuNPs 上丰富。此外，AuNPs 以不同程度诱导了内皮通透性增加，而共聚焦荧光显微镜、Transwell 测定和信号通路测定显示，这种通透性增加被它们的蛋白冠部分抵消。本研究填补了有关具有不断演变形态的纳米颗粒的动态蛋白冠的知识空白，并为未来利用细胞旁途径的纳米医学提供了启示。
