Arsenene: A Potential Therapeutic Agent for Acute Promyelocytic Leukaemia Cells by Acting on Nuclear Proteins

被引:72
作者
Wang, Xiuxiu [1 ]
Hu, Yi [1 ]
Mo, Jianbin [1 ]
Zhang, Jingyi [1 ]
Wang, Zhenzhen [3 ]
Wei, Wei [2 ]
Li, Huanlin [2 ]
Xu, Yun [2 ]
Ma, Jing [1 ]
Zhao, Jing [1 ]
Jin, Zhong [1 ]
Guo, Zijian [1 ]
机构
[1] Nanjing Univ, State Key Lab Coordinat Chem, Key Lab Mesoscop Chem MOE,Sch Chem & Chem Engn, Jiangsu Key Lab Adv Organ Mat,Chem & Biomed Innov, Nanjing 210023, Peoples R China
[2] Nanjing Univ, Sch Life Sci, Nanjing 210023, Peoples R China
[3] Nanjing Univ, Med Sch, Nanjing 210023, Peoples R China
基金
国家重点研发计划; 中国国家自然科学基金;
关键词
antitumor agents; apoptosis; arsenene; nuclear proteins; proteomics; RAMAN-SCATTERING; BI; NANOSHEETS;
D O I
10.1002/anie.201913675
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Arsenene has recently emerged as a promising new two-dimensional material for biomedical applications because of its excellent optical and electronic properties. Herein, novel 2D arsenene nanosheets were synthesized and shown to be effective against NB4 promyelocytic leukaemia (APL) cells (82 % inhibition) as well as inducing apoptosis while showing no toxicity towards normal cells. The high zeta potential, small size, and the planar structure were crucial to the toxicity of the materials. Label-free proteomic profiling analysis suggested that arsenene affected nuclear DNA replication, nucleotide excision repair, and pyrimidine metabolism pathways by downregulating the DNA polymerases POLE, POLD1, POLD2, and POLD3. Mass spectrometric studies showed that arsenene bound mainly to nuclear nucleotide acid binding proteins in NB4 cells and further cellular fluorescence studies revealed that the arsenene destroyed the nuclei. In vivo toxicity tests in mice also indicated the physiological biosafety of arsenene.
引用
收藏
页码:5151 / 5158
页数:8
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