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


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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Fig. 1: BPNS treatment causes mitotic delay and aberrant spindle formation.
Fig. 2: Centrosome defects in BPNS-treated cells.
Fig. 3: Lysosome-mediated centrosome towards trafficking of BPNS during cell cycle.
Fig. 4: BPNS treatment suppresses the mitotic activation of PLK1 kinase at centrosomes.
Fig. 5: BPNS directly binds to PLK1 and induces PLK1 aggregation.
Fig. 6: The anticancer activity of BPNS nanomaterial by inhibiting mitotic progression.

Data availability

The data supporting the findings of this study are available within the paper and its Supplementary Information, and in the Zenodo repository with the identifier Source data are provided with this paper.


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We thank X. Liu (University of Kentucky, USA) for kindly providing Flag/GFP-PLK1 expression plasmids and anti-pS195-Clip-170 antibody. We also thank D. Boraschi (National Research Council of Italy) for critical reading and revision of the manuscript. This work was supported by grants no. 31871366 (to H.L.) and no. 81870174 (to X.S.) from the National Natural Science Foundation of China; grants no. 2021A1515012114 (to X.S.), no. 2018B030308001 (to H.L.) and no. 2016A030312006 (to L. Cai) from the Natural Science Foundation of Guangdong Province; grants no. JCYJ20200109114608075 (to X.S.), no. RCJC20200714114435061 (to X.-F.Y.), no. GJHZ20190821155803877 (to Yang Li) and no. JCYJ20170818153538196 (to W.Su) from Shenzhen Science and Technology Program; and CAS President’s International Fellowship Initiative (PIFI) 2020VBA0028 (to Yang Li).

Author information




H.L., X.-F.Y. and Yang Li conceived the project and supervised the study. X.S. and Z.D. performed most cell biological, biochemical and animal experiments. W.Z., Z.L., H.C., Q.S. and G.W. prepared and characterized the nanomaterials. S.G. prepared the liposomes. B.C. and M.L. assisted with biochemical and animal experiments. Yanyan Li performed the FRAP assay. H.S., X.L. and K.L. performed live-cell imaging. Yanyan Li, X.L., W. Shi, G.C., D.L. and G.Z. participated in cell culture and immunofluorescence staining. X.S., W.Z., L. Chen, W.Su, L.F., L. Cai, D.T.L., Yang Li and X.-F.Y. discussed the data. X.S., W.Z., D.T.L., Yang Li, X.-F.Y. and H.L. wrote the manuscript.

Corresponding authors

Correspondence to Yang Li, Xue-Feng Yu or Hongchang Li.

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The authors declare no competing interests.

Additional information

Peer review information Nature Nanotechnology thanks Matteo Goldoni and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–27, unprocessed gel/blots for supplementary figures, discussion and refs. 1–20.

Reporting Summary

Supplementary Video 1

A representative live-cell movie of control HeLa cells undergoing mitosis.

Supplementary Video 2

A representative live-cell movie of BPNS-treated HeLa cells undergoing mitosis.

Supplementary Video 3

A representative live-cell movie of BPNS-treated HeLa cells undergoing apoptosis after cell division.

Source data

Source Data Fig. 4

Unprocessed western blots.

Source Data Fig. 5

Unprocessed western blots.

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Shao, X., Ding, Z., Zhou, W. et al. Intrinsic bioactivity of black phosphorus nanomaterials on mitotic centrosome destabilization through suppression of PLK1 kinase. Nat. Nanotechnol. 16, 1150–1160 (2021).

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