Hexagonal boron nitride nanodots inhibit cell proliferation of HUVECs and the underlying mechanism

Boron nitride (BN)-based nanomaterials have immense potential in nano-biomedicine, such as drug carriers and anti-bacterial agents. However, their biocompatibility remains a crucial concern. Here, we investigated the cytotoxicity of hexagonal BN (h-BN) nanodots (BNNDs) on HUVEC cells, assessing their effects on viability, morphology, proliferation, cell cycle, genes, and protein expression. BNNDs had limited impact on HUVECs viability, even at high concentrations (200 μg/mL, 48 h). Yet, they hindered cell proliferation and caused cell cycle arrest in the S phase in a dose−/time-dependent manner. Cytotoxicity primarily resulted from disturbances in cell proliferation and DNA replication-related genes (e.g., GADD45A) and proteins (e.g., GADD45A). BNNDs also induced oxidative stress, enhancing cytotoxic effects. Therefore, cautious evaluation of long-term cytotoxicity is crucial before employing BNNDs in biological systems. Additionally, certain dye-based cytotoxicity assessment methods may not accurately reflect the cytotoxicity of BNNDs. Understanding these new cytotoxic mechanisms can aid in designing safer BN-based nano-medicines/devices.