Unraveling the stress-induced toxicity of black phosphorus nanosheets and the underlying mechanism

• 1、School of Radiation Medicine and Protection, Soochow University, Suzhou 215123
• 2、School of Chemical Engineering and Technology, Tiangong University, Tianjin 300387, China

Abstract：The unique physicochemical properties of black phosphorus (BP) nanomaterials make them extremely versatile, and growing concern has emerged regarding their biocompatibility. However, the toxicity of BP nanomaterials has mostly been studied under normal physiological conditions, while the studies on their toxicity under pathological conditions are rather limited. Purpose: To investigate the toxic profile of BP nanosheets under oxidative stress conditions in both living cells and a simple animal model, Caenorhabditis elegans. Results: Under normal conditions, BP nanosheets do not exert any adverse effects on cells and worms. However, BP nanosheets exhibit significant toxicity when cells and worms are under oxidative stress. Further mechanistic studies indicate that hydroxyl radical overproduction is induced by the reaction between BP nanosheets and hydrogen peroxide, which may disrupt mitochondrial integrity and promote the leakage of cytochrome c from mitochondria into cytoplasm. Meanwhile, BP nanosheets were degraded under oxidative stress conditions, providing opportunities for BP nanosheets to interact with cytochrome c, thereby disrupting the cellular antioxidant defense system, ultimately producing toxicity. Conclusion: This researchuncovers the potential mechanism of BP nanosheets with oxidative stress-induced toxicity both in vitro and in vivo, providingimportant safety evidence for the application of BP nanomaterials in biomedical field.

Keywords： Biomedical engineering Black phosphorus nanomaterials Oxidative stress Caenorhabditis elegans Hydroxyl radical Cytochrome c