Cellular uptake and distribution of black phosphorus nanosheets in A549 cells: Effects on cellular metabolism and mitochondrial function

Black phosphorus nanosheets (BPNS) show great potential in medical applications; however, their intracellular behavior and toxic effects should not be ignored once they are introduced into the human body. Fluorescence labeling technology was utilized to visualize their uptake and distribution in A549 cells, and the influence of their sizes was also investigated. This study reveals that small-sized BPNS (SBPNS) and large-sized BPNS (LBPNS) enter cells through macropinocytosis and caveolae-dependent endocytosis respectively. Moreover, BPNS were found to localize in lysosomes (4.17 ± 0.69 μg), the Golgi apparatus (7.65 ± 1.20 μg), and mitochondria (37.20 ± 7.10 μg).Next, the transfer of BPNS to mitochondria causes mitochondrial dysfunction and metabolic disorders, as evidenced by decreased Ca²⁺ levels, decreased mitochondrial membrane potential, cell cycle arrest in S and G2/M phases, and increased ROS levels.The above conclusions provide important basic data to promote the application of BPNS in biomedical fields.