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 regulated 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.