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Intrinsic bioactivity of black phosphorus nanomaterials on mitotic centrosome destabilization through suppression of PLK1 kinase

Shao Ximing,Ding Zhihao,Zhou Wenhua,Li Yanyan,Li Zhibin,Cui Haodong,Lin Xian,Cao Guoli,Cheng Binghua,Sun Haiyan,Li Meiqing,Liu Ke,Lu Danyi,Geng Shengyong,Shi Wenli,Zhang Guofang,Song Qingle,Chen Liang,Wang Guocheng,Su Wu,Cai Lintao,Fang Lijing,Leong David Tai,Li Yang,Yu Xue-Feng,Li Hongchang

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.