Although nanomaterials have shown promising biomedical application potential, incomplete understanding of their molecular interactions with biological systems prevents their inclusion into mainstream clinical applications. Here we show that black phosphorus (BP) nanomaterials directly affect the cell cycle’s centrosome machinery. BP destabilizes mitotic centrosomes by attenuating the cohesion of pericentriolar material and consequently leads to centrosome fragmentation within mitosis. As a result, BP-treated cells exhibit multipolar spindles and mitotic delay, and ultimately undergo apoptosis. Mechanistically, BP compromises centrosome integrity by deactivating the centrosome kinase polo-like kinase 1 (PLK1). BP directly binds to PLK1, inducing its aggregation, decreasing its cytosolic mobility and eventually restricting its recruitment to centrosomes for activation. With this mechanism, BP nanomaterials show great anticancer potential in tumour xenografted mice. Together, our study reveals a molecular mechanism for the tumoricidal properties of BP and proposes a direction for biomedical application of nanomaterials by exploring their intrinsic bioactivities.

尽管纳米材料已显示出有希望的生物医学应用潜力，但对其与生物系统的分子相互作用的不完全了解阻碍了其纳入主流临床应用。在这里，我们证明黑磷（BP）纳米材料直接影响细胞周期的中心体机制。 BP 通过减弱中心粒周围物质的内聚力来破坏有丝分裂中心体的稳定性，从而导致有丝分裂内的中心体破碎。结果，BP处理的细胞表现出多极纺锤体和有丝分裂延迟，并最终发生细胞凋亡。从机制上讲，BP 通过使中心体激酶 polo 样激酶 1 (PLK1) 失活来损害中心体完整性。 BP 直接与 PLK1 结合，诱导其聚集，降低其胞质流动性，并最终限制其招募到中心体进行激活。通过这种机制，BP纳米材料在肿瘤异种移植小鼠中显示出巨大的抗癌潜力。总之，我们的研究揭示了 BP 杀肿瘤特性的分子机制，并通过探索纳米材料的内在生物活性，为纳米材料的生物医学应用提出了方向。