Enzymatic Biodegradability of Pristine and Functionalized Transition Metal Dichalcogenide MoS₂ Nanosheets

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2D transition metal dichalcogenide MoS 2 nanosheets are increasingly attracting interests due to their promising applications in materials science and biomedicine. However, their biocompatibility and their biodegradability have not been thoroughly studied yet. Here, the biodegradability of exfoliated pristine and covalently functionalized MoS 2 ( f ‐MoS 2 ) is investigated. First, biodegradability of these nanomaterials is evaluated using plant horseradish peroxidase and human myeloperoxidase. The results reveal that the enzymatic degradability rate of MoS 2 and f ‐MoS 2 is slower than in the case of the simple treatment with H 2 O 2 alone. In parallel, high biocompatibility of both pristine and f ‐MoS 2 nanosheets is found up to 100 µg mL −1 in both cell lines (HeLa and Raw264.7) and primary immune cells. In addition, no immune cell activation and minimal pro‐inflammatory cytokine release are observed in RAW264.7 and human monocyte‐derived macrophages, suggesting a negligible cellular impact of such materials. Furthermore, the effects of degraded MoS 2 and partially degraded f‐ MoS 2 products on cell viability and activation are studied in cancer and immune cells. A certain cytotoxicity is measured at the highest concentrations. Finally, to prove that the cellular impact is due to cell uptake, the internalization of both pristine and functionalized MoS 2 in cancer and primary immune cells is assessed.