Bioactive phospho-therapy with black phosphorus for in vivo tumor suppression

Bioactive phospho-therapy with black phosphorus for in vivo tumor suppression
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黑磷生物活性磷疗法用于体内肿瘤抑制

DOI:
10.7150/thno.43092
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发表时间:
2020-01-01
期刊:
影响因子:
12.4
通讯作者:
Yu, Xue-Feng
Yu, Xue-Feng
中科院分区:
医学1区
文献类型:
--
作者:
Geng, Shengyong;Pan, Ting;Yu, Xue-Feng

文献摘要

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背景和目的:虽然无机纳米材料已被广泛用于多模式癌症治疗,但材料的内在贡献尚未得到很好的理解,有时被低估。本论文研究了黑磷纳米片(BPs)生物活性磷酸化治疗体内肿瘤的作用。方法:以原位肝肿瘤和急性髓系白血病分别作为实体瘤和血液肿瘤模型。将BP通过尾静脉注射到小鼠中,并通过IVIS生物发光成像监测肿瘤生长。结果:体外研究表明,高细胞内摄取的BPs可诱导人肝癌细胞凋亡和自噬介导的程序性细胞死亡,但对正常细胞无影响。BP以高浓度被动地积聚在肿瘤部位并抑制肿瘤生长。肿瘤重量远小于从多柔比星(DOX)治疗组观察到的重量。平均存活时间延长至少两个月,120天后存活率为100%。Western blot分析证实BPs通过凋亡和自噬途径抑制肿瘤生长。此外,管理的BPs到患有白血病的小鼠的肿瘤抑制和长期survival.Conclusions的结果:这项研究表明,BPs构成一种类型的生物活性抗癌剂,并提供了深入了解无机纳米材料的癌症治疗的应用。
Background and Purpose: Although inorganic nanomaterials have been widely used in multimodal cancer therapies, the intrinsic contributions of the materials are not well understood and sometimes underestimated. In this work, bioactive phospho-therapy with black phosphorus nanosheets (BPs) for in vivo tumor suppression is studied.Methods: Orthotopic liver tumor and acute myeloid leukemia are chosen as the models for the solid tumor and hematological tumor, respectively. BPs are injected into mice through the tail vein and tumor growth is monitored by IVIS bioluminescence imaging. Tumor tissues and serum samples are collected to determine the suppression effect and biosafety of BPs after treatment.Results: The in vitro studies show that BPs with high intracellular uptake produce apoptosis- and autophagy-mediated programmed cell death of human liver carcinoma cells but do not affect normal cells. BPs passively accumulate in the tumor site at a high concentration and inhibit tumor growth. The tumor weight is much less than that observed from the doxorubicin (DOX)-treated group. The average survival time is extended by at least two months and the survival rate is 100% after 120 days. Western bolt analysis confirms that BPs suppress carcinoma growth via the apoptosis and autophagy pathways. In addition, administration of BPs into mice suffering from leukemia results in tumor suppression and long survival.Conclusions: This study reveals that BPs constitute a type of bioactive anti-cancer agents and provides insights into the application of inorganic nanomaterials to cancer therapy.