Intrinsic bioactivity of black phosphorus nanomaterials on mitotic centrosome destabilization through suppression of PLK1 kinase
Intrinsic bioactivity of black phosphorus nanomaterials on mitotic centrosome destabilization through suppression of PLK1 kinase
复制标题
黑磷纳米材料通过抑制 PLK1 激酶对有丝分裂中心体不稳定的内在生物活性
DOI：
10.1038/s41565-021-00952-x
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发表时间：
2021-08-05
影响因子：
38.3
通讯作者：
Li, Hongchang
中科院分区：
文献类型：
--
作者：
Shao, Ximing;Ding, Zhihao;Li, Hongchang
尽管纳米材料显示出有希望的生物医学应用潜力，但对它们与生物系统的分子相互作用的了解不完全，可以阻止它们纳入主流临床应用。在这里，我们表明黑磷（BP）纳米材料直接影响细胞周期的中心体机械。 BP通过减弱丁香元材料的凝聚力来破坏有丝分裂的中心体，从而导致有丝分裂内的中心体碎片。结果，BP处理的细胞表现出多极纺锤体和有丝分裂的延迟，并最终发生凋亡。从机械上讲，BP通过停用中心体激酶类球样激酶1（PLK1）来损害中心体的完整性。 BP直接与PLK1结合，诱导其聚集，降低其胞质迁移率，并最终限制其募集到中心体的激活。通过这种机制，BP纳米材料在肿瘤异种移植小鼠中显示出很大的抗癌潜力。总之，我们的研究揭示了BP的肿瘤特性的分子机制，并通过探索纳米材料的生物医学应用方向，通过探索其固有的生物活性。理解纳米生物生物材料的基本纳米生物材料相互作用，用于生物医学使用的纳米材料相互作用可能会释放潜在的替代应用。在这里，作者揭示了黑磷纳米材料的肿瘤机制，这些纳米材料通过抑制类细性激酶1来直接影响有丝分裂的中心体机械，这表明纳米材料可以用其固有的纳米生物性能应用于靶向癌症治疗中。
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.