具有体外和体内靶向线粒体呼吸的选择性抗白血病活性的金纳米粒子

Gold Nanoparticles with Selective Antileukemic Activity In Vitro and In Vivo Target Mitochondrial Respiration

 

 

 

 

Keywords:mitochondrial membrane potential; oxidative phosphorylation; cytochrome c
关键词:线粒体膜电位;氧化磷酸化;细胞色素c

细胞类型:白血病
作者:Gaiser A, Hafner S, Schmiech M, Büchele B, Schäfer P, Arnim CA, Calzia, E, Feuring‐Buske M, Buske C, Vick B, Jeremias I, Syrovets T, Simmet T
出版期刊:《Advanced Therapeutics》 2019/3/6


Abstract:

This study explores biocompatible amino-functionalized gold nanoparticles (Au-NH2) as nanotherapeutics for the selective eradication of leukemia cells, elucidates the mechanism of cytotoxicity, and it confirms in vivo efficacy of the engineered nanomaterial. Au-NH2 trigger apoptotic cell death of myeloid leukemia cell lines and primary acute myeloid leukemia (AML) cells by i) inhibition of mitochondrial respiration, ii) ATP depletion, iii) loss of mitochondrial membrane potential, and iv) mitochondrial release of cytochrome c. Au-NH2 act selectively on leukemia cells inasmuch as the viability of normal peripheral blood mononuclear cells and macrophages as well as the colony formation of hematopoietic stem cells remain basically unaffected. The selectivity of Au-NH2 for AML cells can be attributed to both the preferential accumulation of AuNH2 in AML cells and the strong dependence of those cells on mitochondrial oxidative phosphorylation for ATP production. Importantly, Au-NH2 applied either as monotherapy or as a cytarabine combination regimen possess antileukemic efficacy in the absence of adverse events in mice xenografted with primary human AML in vivo. The engineered material may pave the way for a novel nanotherapeutic treatment of AML.


文章摘要:

本研究探索了生物相容性氨基功能化金纳米粒子 (Au-NH2) 作为选择性根除白血病细胞的纳米疗法,阐明了细胞毒性机制,并证实了工程纳米材料的体内功效。 Au-NH2 通过以下方式引发髓性白血病细胞系和原发性急性髓性白血病 (AML) 细胞的凋亡性细胞死亡:i) 线粒体呼吸抑制,ii) ATP 耗竭,iii) 线粒体膜电位丧失,以及 iv) 细胞色素 c 的线粒体释放. Au-NH2选择性作用于白血病细胞,正常外周血单个核细胞和巨噬细胞的活力以及造血干细胞的集落形成基本不受影响。 Au-NH2 对 AML 细胞的选择性可归因于 AML 细胞中 AuNH2 的优先积累和这些细胞对线粒体氧化磷酸化产生 ATP 的强烈依赖性。重要的是,在体内异种移植原发性人类 AML 的小鼠中,作为单一疗法或阿糖胞苷联合方案应用的 Au-NH2 在没有不良事件的情况下具有抗白血病功效。这种工程材料可能为 AML 的新型纳米治疗铺平道路。

 


点击链接即可查看和下载文章:https://onlinelibrary.wiley.com/doi/10.1002/adtp.201800149
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