Immunological Responses Induced by Blood Protein Coronas on Two-Dimensional MoS2 Nanosheets
- 13 April 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Nano
- Vol. 14 (5), 5529-5542
- https://doi.org/10.1021/acsnano.9b09744
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 in the MoS2 nanosheets. This can facilitate uptake and produce a stronger pro-inflammatory response in macrophages due to the recognition of NSs-IgG complex by Fc gamma receptors (FcγRs) and the subsequent activation of 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.Keywords
Funding Information
- Ministry of Science and Technology of the People's Republic of China (2016YFA0201600, 2016YFA0203200, 2016YFE0133100)
- National Natural Science Foundation of China (11621505, 11775253, 31971322)
- The World Academy of Sciences
- CAS Key Research Program for Frontier Sciences (QYZDJ-SSW-SLH022)
- Bureau of International Co-operation Chinese Academy of Sciences (GJHG1852)
- Users with Excellence Project of Hefei Science Center CAS (2018HSC-UE004)
- Research and Development Project in Key Areas of Guangdong Province (2019B090917011)
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