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首页> 外文期刊>Journal of drug delivery science and technology >Enhancement mitochondrial apoptosis in breast cancer cells by paclitaxel-triphenylphosphonium conjugate in DNA aptamer modified nanoparticles
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Enhancement mitochondrial apoptosis in breast cancer cells by paclitaxel-triphenylphosphonium conjugate in DNA aptamer modified nanoparticles

机译：紫杉醇三苯基膦酸亚膦酸酯在DNA适体改性纳米粒子中的增强线粒体细胞凋亡

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Mitochondria is a major regulator of inducing tumor apoptosis and it is as a prime target for chemotherapy. Anticancers need to access specific tumor cells and also pass through different barriers such as outer and inner membranes of mitochondria. Targeted accumulation of paclitaxel (PTX) within the mitochondria was achieved by direct conjugation of PTX with triphenylphosphonium (TPP) as a mitochondrial membrane-permeable cation. PTX-TPP prodrug was synthesized by pH-sensitive ester bond between the hydroxyl function of PTX and the carboxylic function of TPP. This ester bond is only cleaved by the mitochondrial aldehyde dehydrogenase. Prodrug was loaded in the albumin nanoparticles by nab-technology. The surface aptamer modification of nanoparticles was done by MUC1 DNA aptamer in order to targeting of tumor cells overexpressing MUC1. The yield of PTX-TPP conjugation was 81% and the particle size of final nanoparticles was 139 nm. The aptamer-modified nanoparticles significantly increased the cellular uptake to 99.9%, and demonstrated good mitochondrial uptake in the confocal fluorescence images leading to apoptosis of MCF-7 breast cancer cells. Early apoptosis and late apoptotic/necrotic phase of cells after 24 h were 26.4% and 25.3%, respectively, compared to 5.27% and 4.74% for free PTX. The targeted nanoparticles exhibited the superior in vitro anticancer efficacy of up to 17.8 fold higher than free PTX after 72 h. This multi-targeting strategy induced the mitochondrial apoptosis to killing tumor cells.
机译：线粒体是诱导肿瘤细胞凋亡的主要调节因子，它是化疗的主要目标。抗癌需要进入特异性肿瘤细胞，并且还通过不同的屏障，例如线粒体的外膜和内膜。通过用三苯基鏻（TPP）直接缀合PTX作为线粒体膜渗透阳离子，通过直接缀合PAClitaxel（PTX）的靶向积累。通过PTX的羟基函数与TPP的羧功能之间的pH-敏感酯键合成PTX-TPP前药。该酯键仅被线粒体醛脱氢酶切割。通过Nab技术在白蛋白纳米粒子中装入前药。纳米颗粒的表面适体改性通过MUC1 DNA适体进行，以靶向过表达MUC1的肿瘤细胞。 PTX-TPP缀合的产率为81％，最终纳米颗粒的粒度为139nm。适体改性的纳米颗粒显着增加了细胞摄取至99.9％，并在共聚焦荧光图像中显示出良好的线粒体摄取，导致MCF-7乳腺癌细胞凋亡。 24小时后细胞早期的细胞凋亡和细胞晚凋亡/坏死阶段分别为26.4％和25.3％，而游离PTX的5.27％和4.74％。靶向纳米颗粒在72小时后表现出比游离PTX高达17.8倍的优异体外抗癌效果。这种多目标战略诱导了对杀死肿瘤细胞的线粒体细胞凋亡。

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