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

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 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.

Deep exploration of random forest model boosts the interpretability of machine learning studies of complicated immune responses and lung burden of nanoparticles

“…S22, C and D). The SSA of NPs will allow the particles to adsorb proteins and form NP-protein corona complexes, which mediate immune responses ( 35 ). NPs with a large SSA are more likely to be internalized by the cell, thus causing a decrease in the number of molecules released by the cell ( 36 ).…”

Recent Advances in Immunosafety and Nanoinformatics of Two-Dimensional Materials Applied to Nano-imaging

“…As far as it is known, 2D materials have proven their significance and innovation perspective in almost all industrial areas and sectors, making it imperative to assess their environmental health risks and safety aspects (24,(103)(104)(105). However, toxicological studies, including immunotoxicity, are still in their infancy for GBMs and 2D inorganic materials (31). Table 1 is an extensive literature revision reporting major findings of 2D materials and their adverse effects in the immunological system considering in vitro and in vivo models.…”

“…Biocompatibility, biodegradability, and eliciting an adequate biological effect in the organisms are crucial to the applicability of 2D materials (22,24,31). Indeed, the complexity of toxicokinetic and toxicodynamic events of 2D materials under physiological conditions associated with a lack of harmonized protocols for experimental research represents majors challenges for clinical translation and safety regulation involving these emerging materials (32)(33)(34)(35).…”

Spike Protein Targeting “Nano-Glue” that Captures and Promotes SARS-CoV-2 Elimination

“…4j-k). Since β -sheet structures promote protein adsorption on the NS 41 , this may explain the preferential binding of RBD to CIPS. A conformational change in RBD upon CIPS binding was also observed (Fig.…”