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

  • Nat Nanotechnol. 2021 Oct;16(10):1150-1160. doi: 10.1038/s41565-021-00952-x.
Ximing Shao   #  1  2 ,  Zhihao Ding   #  1  2 ,  Wenhua Zhou  1 ,  Yanyan Li  1  3 ,  Zhibin Li  1 ,  Haodong Cui  1 ,  Xian Lin  1 ,  Guoli Cao  1 ,  Binghua Cheng  1  3 ,  Haiyan Sun  1 ,  Meiqing Li  1  3 ,  Ke Liu  1  2 ,  Danyi Lu  1 ,  Shengyong Geng  1 ,  Wenli Shi  1  4 ,  Guofang Zhang  1 ,  Qingle Song  1 ,  Liang Chen  1 ,  Guocheng Wang  1 ,  Wu Su  1 ,  Lintao Cai  1  2 ,  Lijing Fang  1 ,  David Tai Leong  5 ,  Yang Li  6 ,  Xue-Feng Yu  7 ,  Hongchang Li  8  9  10
Affiliations
  • 1. Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • 2. Guangdong Key Laboratory of Nanomedicine, Shenzhen, China.
  • 3. University of Chinese Academy of Sciences, Beijing, China.
  • 4. Hainan University, Haikou, China.
  • 5. Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, Singapore.
  • 6. Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. [email protected].
  • 7. Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. [email protected].
  • 8. Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. [email protected].
  • 9. Guangdong Key Laboratory of Nanomedicine, Shenzhen, China. [email protected].
  • 10. Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen, China. [email protected].
  • # Contributed equally.
PMID: 34354264 DOI: 10.1038/s41565-021-00952-x
Abstract

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.

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