Autophagy-targeted therapy for pulmonary inflammation by 2D MX₂ (M = W, Nb; X = S, Se) nanosheets

For biomedical applications, two-dimensional transition metal dichalcogenides (2D TMDCs) are often combined with other elements or functionalized with specific surface ligands, while their intrinsic biological activities are not yet fully understood. This study investigates the anti-inflammatory potential of four unmodified 2D TMDCs, including WS₂, WSe₂, NbS₂, and NbSe₂ nanosheets, in LPS-activated MH-S cells in vitro and in a mouse model of pulmonary inflammation in vivo. Despite their varying compositions, these 2D TMDCs exhibited comparable anti-inflammatory effects in LPS-activated MH-S cells. Notably, the 2D TMDC nanosheets disrupted autophagic signaling pathways by adhering to the cell membrane and/or being internalized by the cells, thereby enhancing cellular autophagy and reducing the LPS-induced pro-inflammatory response by inhibiting NFκB phosphorylation. Their natural affinity for lung tissue makes these 2D TMDCs promising therapeutic agents for pulmonary inflammation, a finding further supported by results from the LPS-induced mouse model. Importantly, these results highlight the critical role of composition in the effects of 2D TMDCs on autophagic signaling, which could significantly advance the development of personalized therapies for pulmonary inflammation. STATEMENT OF SIGNIFICANCE: Autophagy represents a promising target for therapeutic intervention in inflammatory lung diseases. This study explores various pristine two-dimensional transition metal dichalcogenides (2D TMDCs) as regulators of autophagy for targeted therapy in pulmonary inflammation. It emphasizes the crucial role of composition in shaping the effects of 2D TMDCs on autophagic signaling, thereby advancing the development of personalized therapies for pulmonary inflammation.