Biodegradation of Hexagonal Boron Nitride Nanomaterials by Neutrophils

The biodegradation of hexagonal boron nitride (h-BN) nanomaterials by neutrophils was investigated. After incubation for 36 h, h-BN nanosheets are taken up by neutrophils, and their structure is highly disrupted, as observed via high-resolution transmission electron microscopy (HR-TEM) and confocal Raman imaging. Among the three degradation pathways, the release of neutrophil extracellular traps from neutrophils is the dominant, with myeloperoxidase (MPO) playing an important role. Molecular dynamics simulations show that MPO spontaneously attach onto h-BN surface, and leverage the active sites of MPO to form favorable contacts with h-BN to initiate the degradation. Hypochlorite produced by MPO is responsible for h-BN degradation. With the assistance of hypochlorite, B–O and N–O bonds are formed on h-BN, along with B–N bond breakage and the release of ionic boron and nitrogen based on byproduct identification and first-principle calculations. Additionally, h-BN nanosheets are significantly degraded into small pieces, and the particle concentration of h-BN with a size of 0–100 nm increases by 58.7% after degradation. Following degradation, h-BN nanosheets induce significant hemolysis of red blood cells, and exhibit higher cytotoxicity against epithelial cells. Our findings highlight the importance of considering h-BN degradation for its safe application, and demonstrate the actual risk of h-BN in biological and natural environments.