Pulmonary effect of 2D MXenes in mice: Immune cell responses and disrupted hematopoiesis

V₂C is a type of two-dimensional transition metal carbide (MXene) with rapidly expanding applications in energy, sensor, electronic information, and biomedicine. However, compared with Ti₃C₂, its health risk assessment remains inconclusive, posing a potential constraint on its further application. In this study, we examined immune and hematopoietic alterations in adult mice following pulmonary exposure to V₂C nanosheets (NSs) on days 1 and 7, using Ti₃C₂ NSs as a reference. Exposure to V₂C NSs induced a sustained elevation of neutrophils in the blood, lung, and bone marrow. This response differed markedly from the transient neutrophil increase followed by monocyte-mediated resolution observed with Ti₃C₂ NSs. Both MXenes upregulated G-csf in lung to activate emergency granulopoiesis, associated with reduced lung granulocyte-monocyte progenitors (GMPs) but expanded bone-marrow GMPs on day 1. By day 7, this effect persisted in V₂C NSs, whereas Ti₃C₂ NSs increased lung GMPs as G-csf returned to baseline and selectively induced Mcp-1 and modulated Il-1β, thereby promoting monocyte recruitment and regulating myelopoiesis. Compared with the in vitro high biocompatibility of Ti₃C₂ NSs, V₂C NSs exhibited pronounced cytotoxicity and elevated reactive oxygen species. Our study implied that V₂C NSs demonstrated higher pulmonary immunotoxicity via persistent, neutrophil-driven inflammation due to the different chemical composition and biological activity from Ti₃C₂ NSs. This emphasized the need for tailored safety evaluations in the development and application of emerging nanomaterials.