Biodistribution, inter-/intra-cellular localization and respiratory dysfunction induced by Ti3C2 nanosheets: Involvement of surfactant protein down-regulation in alveolar epithelial cells

Two-dimensional Ti3C2 nanosheets have been extensively used in biomedical fields and are mostly designed to enter the circulatory system. However, few studies have focused on the in vivo anatomical location and physi-ological function of major organs on exposure to Ti3C2 nanosheets. This study attempts to determine whether and how Ti3C2 nanosheets disrupt the physiological function of the involved organs. Our studies demonstrated that Ti3C2 nanosheets were mainly distributed in the lungs and liver after entering circulation. In the lungs, they were retained in the cytoplasm of alveolar epithelial cells and endothelial cells, and inhibited pulmonary surfactant protein B (SP-B) expression on alveolar epithelial cell, causing increased airway resistance-induced respiratory disorder following a 28-day Ti3C2 nanosheet exposure. Furthermore, our data showed that Ti3C2 nanosheets did not cause abnormal proinflammatory cytokines and histopathological changes. These findings demonstrated that Ti3C2 nanosheets might disturb respiration without inflammatory responses and pathological lesions, suggesting that these effects may occur by decreasing SP-B-mediated airway resistance. This indicates that organ function maintenance differs from biological safety for Ti3C2 nanosheets, an important consideration during potential clinical application and human exposure.