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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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).
The authors declare no competing interests.
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 Figs. 1–27, unprocessed gel/blots for supplementary figures, discussion and refs. 1–20.
A representative live-cell movie of control HeLa cells undergoing mitosis.
A representative live-cell movie of BPNS-treated HeLa cells undergoing mitosis.
A representative live-cell movie of BPNS-treated HeLa cells undergoing apoptosis after cell division.
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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). https://doi.org/10.1038/s41565-021-00952-x