Han Chao, Xu Xiao, Zhang Can, Yan Dan, Liao Shanting, Zhang Chao, Kong Lingyi
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
State Key Laboratory of Natural Medicines, Center of Drug Discovery and Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
Biosens Bioelectron. 2021 Feb 1;173:112791. doi: 10.1016/j.bios.2020.112791. Epub 2020 Nov 5.
Targeting mitochondria-mediated apoptosis has emerged as a promising strategy for tumor therapy. However, technologies used to treat tumors that enable the direct visualization of mitochondria-mediated apoptosis in living cells have not been developed to date. Cytochrome c (Cyt c) translocation from mitochondria is a central mediating event in cell apoptosis. In this study, we developed a multifunctional nanosensor that can monitor the real-time translocation of Cyt c from mitochondria in living cells to evaluate the antitumor effect of dihydroartemisinin (DHA). A fluorophore-tagged DNA aptamer is loaded on a graphene oxide (GO)-based nanovehicle, and the cytosolic release of Cyt c causes the dissociation of the aptamer from the GO nanovehicle and triggers the emission of a red fluorescence signal. Furthermore, DHA linked with a coumarin derivative is loaded on GO as a mitochondria-targeting ligand to improve its antitumor activity. This DHA prodrug also emits a green fluorescence signal when delivered to mitochondria. This nanosensor provides a convenient mechanism to monitor mitochondrial targeting by drugs and mitochondria-induced therapeutic efficacy, which may be possible to diagnose the drug efficacy to optimize the treatment for patients with cancer.
靶向线粒体介导的细胞凋亡已成为一种很有前景的肿瘤治疗策略。然而，迄今为止，尚未开发出能够直接可视化活细胞中线粒体介导的细胞凋亡的肿瘤治疗技术。细胞色素c（Cyt c）从线粒体的转位是细胞凋亡中的一个核心介导事件。在本研究中，我们开发了一种多功能纳米传感器，它可以监测活细胞中Cyt c从线粒体的实时转位，以评估双氢青蒿素（DHA）的抗肿瘤效果。一种荧光团标记的DNA适体被负载在基于氧化石墨烯（GO）的纳米载体上，Cyt c的胞质释放导致适体从GO纳米载体上解离，并触发红色荧光信号的发射。此外，与香豆素衍生物连接的DHA作为线粒体靶向配体负载在GO上，以提高其抗肿瘤活性。这种DHA前药在递送至线粒体时也会发出绿色荧光信号。这种纳米传感器提供了一种方便的机制来监测药物的线粒体靶向作用和线粒体诱导的治疗效果，这可能有助于诊断药物疗效，从而优化癌症患者的治疗方案。
