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 (V 2 C QDs) that are capable of crossing the BBB are prepared, and the admirable anti‐neuroinflammatory effects are presented. The prepared 2D V 2 C QDs with an average size of 2.54 nm show good hydrophilicity, physiological stability, and effective BBB‐crossing ability. The biological effect of V 2 C 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 V 2 C 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, V 2 C QDs exert potent anti‐inflammatory effects through multiple pathways, thus offer great potential for the treatment of neurodegenerative diseases.