Immunological Responses Induced by Blood Protein Coronas on Two-Dimensional MoS2 Nanosheets

作者：Didar Baimanov, Junguang Wu, Runxuan Chu, Rong Cai, Bing Wang, Mingjing Cao, Ye Tao, Jiaming Liu, Mengyu Guo, Jing Wang, Xia Yuan, Chendong Ji, Yuliang Zhao, Weiyue Feng, Liming Wang, Chunying Chen · 发表于：ACS Nano · 年份：2020 · DOI：10.1021/acsnano.9b09744 · 被引用次数：129 · 研究领域：Advanced biosensing and bioanalysis techniques、RNA Interference and Gene Delivery、Extracellular vesicles in disease

Abstract Two-dimensional (2D) nanosheets (NSs) have a large surface area, high surface free energy, and ultrathin structure, which enable them to more easily penetrate biological membranes and promote adsorption of drugs and proteins. NSs are capable of adsorbing a large amount of blood proteins to form NSs–protein corona complexes; however, their inflammatory effects are still unknown. Therefore, we investigated the pro-inflammatory effect of 2D model nanosheet structures, molybdenum disulfide (MoS2), and the MoS2 NSs–protein complexes with four abundant proteins in human blood, i.e., human serum albumin (HSA), transferrin (Tf), fibrinogen (Fg), and immunoglobulin G (IgG). The interactions between the NSs and the proteins were analyzed by quantifying protein adsorption, determining binding affinity, and correlating structural changes in the protein corona with the uptake of NSs by macrophages and the subsequent inflammatory response. Although all of the NSs–protein complexes induced inflammation, IgG-coated and Fg-coated NSs triggered much stronger inflammatory effects by producing and releasing more cytokines. Among the four proteins, IgG possessed the highest proportion of β-sheets and led to fewer secondary structure changes on the MoS2 nanosheets. This can facilitate uptake and produce a stronger pro-inflammatory response in macrophages due to the recognition of an NSs–IgG complex by Fc gamma receptors and the subsequent activation of the NF-κB pathways. Our results demo...