Department of Nanotechnology & Nanomedicine, Hacettepe University, Ankara, Turkey.
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nanomedicine (Lond). 2017 Aug;12(16):1961-1973. doi: 10.2217/nnm-2017-0081. Epub 2017 Jul 26.
In this study, we aimed to therapeutically target eukaryotic elongation factor 2 kinase (eEF-2K) in an in vivo triple-negative breast cancer (TNBC) tumor model.
MATERIALS & METHODS: We synthesized a highly monodisperse nanoformulation using polyethylenimine-modified gold nanoparticles (AuNP-PEI) as siRNA delivery vehicle and evaluated gene downregulation.
We found that AuNP-PEI/eEF-2K nanoformulation was highly effective for in vitro and in vivo gene downregulation and showed remarkable antitumor efficacy that was associated with eEF-2K knockdown, inhibition of Src and MAPK-ERK signaling pathways in a TNBC orthotopic tumor model.
Our study suggests that eEF-2K plays an important role in TNBC tumorigenesis and its inhibition by AuNP-PEI/eEF-2K siRNA-based nanotherapeutics may be a potential therapeutic strategy for TNBC.
本研究旨在体内三阴性乳腺癌(TNBC)肿瘤模型中靶向真核延伸因子 2 激酶(eEF-2K)进行治疗。
我们使用聚乙二醇化修饰的金纳米颗粒(AuNP-PEI)作为 siRNA 递送载体合成了一种高单分散纳米制剂,并评估了基因下调。
我们发现 AuNP-PEI/eEF-2K 纳米制剂在体外和体内均具有高效的基因下调作用,并显示出显著的抗肿瘤疗效,这与 eEF-2K 敲低、Src 和 MAPK-ERK 信号通路抑制有关在 TNBC 原位肿瘤模型中。
我们的研究表明,eEF-2K 在 TNBC 肿瘤发生中起重要作用,其通过 AuNP-PEI/eEF-2K siRNA 纳米疗法的抑制可能是 TNBC 的一种潜在治疗策略。