研究动态
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通过铜掺杂碳点阻断金属硫蛋白-2 表达可诱导细胞抗氧化系统崩溃,用于抗肿瘤治疗。

Blocking Metallothionein-2 Expression by Copper-Doped Carbon Dots Induces Cellular Antioxidant System Collapse for Antitumor Therapy.

发表日期:2024 Aug 14
作者: Kexuan Liu, Xinchen Liu, Linlin Wen, Wenhao Zhai, Rongrong Ye, Boya Zhang, Wangni Xie, Xue Zhang, Wenbing Zhang, Haiqiu Li, Jiaqi Xu, Lei Huang, Huan Wang, Daowei Li, Hongchen Sun
来源: ANTIOXIDANTS & REDOX SIGNALING

摘要:

肿瘤细胞中抗氧化剂储备不足在活性氧(ROS)介导的治疗中发挥着关键作用。金属硫蛋白-2 (MT-2) 是一种富含半胱氨酸的细胞内蛋白质,以其有效的抗氧化特性而闻名,与肿瘤的发展密切相关,并与不良预后相关。因此,MT-2 成为肿瘤治疗的一个有前景的靶标。在此,我们展示了铜掺杂碳点 (Cu-CD) 的开发,以靶向 MT-2,以损害肿瘤细胞中脆弱的抗氧化剂储备。这些Cu-CDs具有较高的肿瘤积累性和较长的体内滞留时间,可以通过诱导氧化应激来有效抑制肿瘤的生长。转录组测序揭示了体内肿瘤样本中 MT-2 表达的显着下降。进一步的力学研究表明,Cu-CD 的抗肿瘤作用与载脂蛋白 E (ApoE) 介导的 MT-2 表达下调和抗氧化系统崩溃密切相关。 Cu-CD 强大的抗肿瘤功效为开发用于癌症治疗的 MT-2 靶向纳米药物提供了宝贵的见解。
The insufficient antioxidant reserves in tumor cells play a critical role in reactive oxygen species (ROS)-mediated therapeutics. Metallothionein-2 (MT-2), an intracellular cysteine-rich protein renowned for its potent antioxidant properties, is intricately involved in tumor development and correlates with a poor prognosis. Consequently, MT-2 emerges as a promising target for tumor therapy. Herein, we present the development of copper-doped carbon dots (Cu-CDs) to target MT-2 to compromise the delicate antioxidant reserves in tumor cells. These Cu-CDs with high tumor accumulation and prolonged body retention can effectively suppress tumor growth by inducing oxidative stress. Transcriptome sequencing unveils a significant decrease in MT-2 expression within the in vivo tumor samples. Further mechanical investigations demonstrate that the antitumor effect of Cu-CDs is intricately linked to apolipoprotein E (ApoE)-mediated downregulation of MT-2 expression and the collapse of the antioxidant system. The robust antitumor efficacy of Cu-CDs provides invaluable insights into developing MT-2-targeted nanomedicine for cancer therapies.