Baimanov Didar, Wu Junguang, Chu Runxuan, Cai Rong, Wang Bing, Cao Mingjing, Tao Ye, Liu Jiaming, Guo Mengyu, Wang Jing, Yuan Xia, Ji Chendong, Zhao Yuliang, Feng Weiyue, Wang Liming, Chen Chunying
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
ACS Nano. 2020 May 26;14(5):5529-5542. doi: 10.1021/acsnano.9b09744. Epub 2020 Apr 29.
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 (MoS), and the MoS NSs-protein complexes with four abundant proteins in human blood, .., 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 MoS 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 demonstrate that the blood protein components contribute to the inflammatory effects of nanosheets and provide important insights for the nanosafety evaluation and the rational design of nanomedicines in the future.
二维（2D）纳米片（NSs）具有大表面积、高表面自由能和超薄结构，这使它们能够更轻松地穿透生物膜并促进药物和蛋白质的吸附。纳米片能够吸附大量血液蛋白质以形成纳米片-蛋白质冠复合物；然而，它们的炎症效应仍不清楚。因此，我们研究了二维模型纳米片结构二硫化钼（MoS₂）以及MoS₂纳米片与人类血液中四种丰富蛋白质（即人血清白蛋白（HSA）、转铁蛋白（Tf）、纤维蛋白原（Fg）和免疫球蛋白G（IgG））形成的MoS₂纳米片-蛋白质复合物的促炎作用。通过定量蛋白质吸附、测定结合亲和力以及将蛋白质冠层的结构变化与巨噬细胞对纳米片的摄取及随后的炎症反应相关联，分析了纳米片与蛋白质之间的相互作用。尽管所有纳米片-蛋白质复合物均诱导炎症，但IgG包被和Fg包被的纳米片通过产生和释放更多细胞因子引发更强的炎症效应。在这四种蛋白质中，IgG具有最高比例的β折叠，并且导致MoS₂纳米片上二级结构变化较少。由于Fcγ受体识别纳米片-IgG复合物并随后激活NF-κB途径，这可促进巨噬细胞摄取并产生更强的促炎反应。我们的结果表明血液蛋白质成分促成了纳米片的炎症效应，并为未来纳米安全性评估和纳米药物的合理设计提供了重要见解。
