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Arsenene: A Potential Therapeutic Agent for Acute Promyelocytic Leukaemia Cells by Acting on Nuclear Proteins
Author(s) -
Wang Xiuxiu,
Hu Yi,
Mo Jianbin,
Zhang Jingyi,
Wang Zhenzhen,
Wei Wei,
Li Huanlin,
Xu Yun,
Ma Jing,
Zhao Jing,
Jin Zhong,
Guo Zijian
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201913675
Subject(s) - dna , nucleotide , dna damage , polymerase , dna replication , chemistry , biophysics , microbiology and biotechnology , biology , biochemistry , gene
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.