Vanadium Carbide Quantum Dots Exert Efficient Anti‐Inflammatory Effects in Lipopolysaccharide‐Induced BV2 Microglia and Mice

The regulation of glial cell activation is a critical step for the treatment or prevention of neuroinflammation-based brain diseases. However, the development of therapeutic drugs that pass the blood-brain barrier (BBB) and inhibit the glia cell activation remains a significant challenge. Herein, an ultrasmall 2D vanadium carbide quantum dots (V₂C QDs) that are capable of crossing the BBB are prepared, and the admirable anti-neuroinflammatory effects are presented. The prepared 2D V₂C QDs with an average size of 2.54 nm show good hydrophilicity, physiological stability, and effective BBB-crossing ability. The biological effect of V₂C QDs on inflammatory reactions demonstrates fascinating results in preventing the impairment of learning and memory in BALB/c mice stimulated by lipopolysaccharide. Investigation of molecular mechanism reveals that V₂C QDs not only inhibit the toll-like receptor 4/myeloid differentiation factor 88-mediated nuclear factor kappa B and mitogen-activated protein kinase pathways, but also prevent eukaryotic translation initiation factor 2α/activating transcription factor 4/C/EBP homologous protein-signaling pathway and reduce oxidative stress via activating the NF-E2-related factor-2/heme oxygenase-1-signaling pathway, leading to greatly inhibited activation of microglia and astrocytes and weakened production of inflammatory cytokines. In summary, V₂C QDs exert potent anti-inflammatory effects through multiple pathways, thus offer great potential for the treatment of neurodegenerative diseases.