Black phosphorus nanomaterials induce hepatic lipid metabolism disorders by triggering oxidative stress and mitochondrial dysfunction

Black phosphorus is the most stable allotrope of phosphorus and possesses a unique layered structure. Black phosphorus nanosheets and black phosphorus quantum dots are the two main forms of black phosphorus nanomaterials (BPNM). BPNM hold significant application potential across various fields, yet a comprehensive evaluation of their biosafety, particularly the impact on hepatic metabolism, remains insufficient. This study investigates the hepatotoxic effects and mechanisms induced by BPNM, with a focus on lipid metabolic disorders. Following a 28-day daily oral administration of black phosphorus quantum dots or black phosphorus nanosheets at doses of 0.1 and 1 mg/kg, mice exhibited reduced insulin sensitivity, increased inflammatory responses, decreased serum levels of triglycerides and very-low-density lipoprotein (VLDL), and exacerbated hepatic lipid accumulation. RNA-sequencing revealed that oxidative stress is a key contributor to BPNM-induced metabolic disruption, accompanied by severe mitochondrial dysfunction. Similarly, BPNM exposure also elevated intracellular reactive oxygen species (ROS), impaired mitochondrial respiratory function and ATP production, consequently disrupted VLDL assembly and secretion in AML12 hepatocyte line. Moreover, ROS scavenger and ATP supplementation restored mitochondrial function and triglycerides transport in vitro. Findings demonstrate that BPNM promote hepatic lipid accumulation possibly by triggering oxidative stress and impairing mitochondrial function, thereby interfering with lipid transport, and resulting in hepatic lipid accumulation. This study highlights the potential metabolic disruption risks of BPNM and provides critical insights for their biosafety assessment and sustainable application.