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

Published on Aug 5, 2021in Nature Nanotechnology31.538
· DOI :10.1038/S41565-021-00952-X
Ximing Shao5
Estimated H-index: 5
(CAS: Chinese Academy of Sciences),
Zhihao Ding5
Estimated H-index: 5
(CAS: Chinese Academy of Sciences)
+ 23 AuthorsHaiyan Sun3
Estimated H-index: 3
(CAS: Chinese Academy of Sciences)
Sources
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.
📖 Papers frequently viewed together
22 Citations
133 Citations
References50
Newest
#1Saara HämälistöH-Index: 4
Last. Marja Jäättelä (UCPH: University of Copenhagen)H-Index: 94
view all 12 authors...
Lysosomes are membrane-surrounded cytoplasmic organelles filled with a powerful cocktail of hydrolases. Besides degrading cellular constituents inside the lysosomal lumen, lysosomal hydrolases promote tissue remodeling when delivered to the extracellular space and cell death when released to the cytosol. Here, we show that spatially and temporally controlled lysosomal leakage contributes to the accurate chromosome segregation in normal mammalian cell division. One or more chromatin-proximal lyso...
24 CitationsSource
#1Jie Kai Tee (NUS: National University of Singapore)H-Index: 8
#2Li Xian Yip (NUS: National University of Singapore)H-Index: 1
Last. David Tai Leong (NUS: National University of Singapore)H-Index: 63
view all 8 authors...
The ever-growing use of inorganic nanoparticles (NPs) in biomedicine provides an exciting approach to develop novel imaging and drug delivery systems, owing to the ease with which these NPs can be functionalized to cater to various applications. In cancer therapeutics, nanomedicine generally relies on the enhanced permeability and retention (EPR) effect observed in tumour vasculature to deliver anti-cancer drugs across the endothelium. However, such a phenomenon is dependent on the tumour microe...
110 CitationsSource
#1Chang Liu (CAS: Chinese Academy of Sciences)H-Index: 1
#2Xingjie Hu (Guangzhou Medical University)H-Index: 7
Last. Haiyun Song (CAS: Chinese Academy of Sciences)H-Index: 21
view all 7 authors...
Nanoparticles (NPs) can interact with a large variety of endogenous proteins upon entering a living system. However, the effects of NP adsorption on protein functions and consequent cellular behaviors are poorly understood. Here, a mass spectrometry analysis is applied to delineate a proteome-scale map of the nanodiamond (ND) interactome network in cancer cells, which identifies the transforming growth factor β (TGFβ) type II receptor (TβRII) as a high affinity binding partner. Further investiga...
7 CitationsSource
#1Fei Peng (NUS: National University of Singapore)H-Index: 24
#2Magdiel Inggrid Setyawati (NUS: National University of Singapore)H-Index: 33
Last. David Tai Leong (NUS: National University of Singapore)H-Index: 63
view all 8 authors...
While most cancer nanomedicine is designed to eliminate cancer, the nanomaterial per se can lead to the formation of micrometre-sized gaps in the blood vessel endothelial walls. Nanomaterials-induced endothelial leakiness (NanoEL) might favour intravasation of surviving cancer cells into the surrounding vasculature and subsequently extravasation, accelerating metastasis. Here, we show that nanoparticles induce endothelial leakiness through disruption of the VE-cadherin–VE-cadherin homophilic int...
204 CitationsSource
#1Vivian P. Vu (UM: University of Montana)H-Index: 5
#2Geoffrey Gifford (UM: University of Montana)H-Index: 2
Last. Dmitri Simberg (UM: University of Montana)H-Index: 30
view all 10 authors...
Deposition of complement factors (opsonization) on nanoparticles may promote clearance from the blood by macrophages and trigger proinflammatory responses, but the mechanisms regulating the efficiency of complement activation are poorly understood. We previously demonstrated that opsonization of superparamagnetic iron oxide (SPIO) nanoworms with the third complement protein (C3) was dependent on the biomolecule corona of the nanoparticles. Here we show that natural antibodies play a critical rol...
103 CitationsSource
#1Wenhua Zhou (CAS: Chinese Academy of Sciences)H-Index: 12
#2Ting Pan (CAS: Chinese Academy of Sciences)H-Index: 4
Last. Xue-Feng Yu (CAS: Chinese Academy of Sciences)H-Index: 53
view all 6 authors...
: Black phosphorus nanosheets (BPs) are demonstrated to be highly bioactive anti-cancer agents because of their inherent and selective chemotherapeutic effects. Fast intracellular biodegradation of BPs and acute elevation of phosphate anions were observed from different types of cancer cells due to the stronger intracellular oxidative stress and accelerated energy metabolism, but normal cells are not affected. Selective biodegradation of BPs induced G2/M phase arrest and subsequent apoptosis- an...
65 CitationsSource
#1Jayanta Kumar Patra (Dongguk University)H-Index: 32
#2Gitishree Das (Dongguk University)H-Index: 17
Last. Han-Seung Shin (Dongguk University)H-Index: 28
view all 12 authors...
Nanomedicine and nano delivery systems are a relatively new but rapidly developing science where materials in the nanoscale range are employed to serve as means of diagnostic tools or to deliver therapeutic agents to specific targeted sites in a controlled manner. Nanotechnology offers multiple benefits in treating chronic human diseases by site-specific, and target-oriented delivery of precise medicines. Recently, there are a number of outstanding applications of the nanomedicine (chemotherapeu...
1,144 CitationsSource
#1Dong-Hoon Kim (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 27
#2Je Min Yoo (SNU: Seoul National University)H-Index: 9
Last. Han Seok KoH-Index: 33
view all 22 authors...
Graphene quantum dots inhibit the formation of alpha-synuclein fibrils and induce their dissociation in vitro, and display neuro-protective properties in in vivo models of Parkinson’s disease, with no appreciable long-term toxicity.
156 CitationsSource
#1Bengt Fadeel (KI: Karolinska Institutet)H-Index: 17
#2Lucian FarcalH-Index: 6
Last. Kai Savolainen (Finnish Institute of Occupational Health)H-Index: 37
view all 10 authors...
Engineered nanomaterials (ENMs) have tremendous potential to produce beneficial technological impact in numerous sectors in society. Safety assessment is, of course, of paramount importance. However, the myriad variations of ENM properties makes the identification of specific features driving toxicity challenging. At the same time, reducing animal tests by introducing alternative and/or predictive in vitro and in silico methods has become a priority. It is important to embrace these new advances...
115 CitationsSource
#1Jianbin Mo (NU: Nanjing University)H-Index: 4
#2Qingyun XieH-Index: 1
Last. Jing Zhao (NU: Nanjing University)H-Index: 56
view all 4 authors...
The increasing number of biological applications for black phosphorus (BP) nanomaterials has precipitated considerable concern about their interactions with physiological systems. Here we demonstrate the adsorption of plasma protein onto BP nanomaterials and the subsequent immune perturbation effect on macrophages. Using liquid chromatography tandem mass spectrometry, 75.8% of the proteins bound to BP quantum dots were immune relevant proteins, while that percentage for BP nanosheet–corona compl...
79 CitationsSource
Cited By1
Newest
Due to their prominent physicochemical properties, 2D materials are broadly applied in biomedicine. Currently, 2D materials have achieved great success in treating many diseases such as cancer and tissue engineering as well as bone therapy. Based on their different characteristics, 2D materials could function in various ways in different bone diseases. Herein, the application of 2D materials in bone tissue engineering, joint lubrication, infection of orthopedic implants, bone tumors, and osteoar...
Source