纳米医学
卵巢癌
癌症研究
医学
转移
细胞凋亡
癌症
药理学
癌细胞
化学
内科学
纳米技术
材料科学
生物化学
纳米颗粒
作者
Xiuyu Huang,Miaojuan Qiu,Tianqi Wang,Binbin Li,Shiqiang Zhang,Tianzhi Zhang,Peng Liu,Qiang Wang,Zhi Rong Qian,Chengming Zhu,Meiying Wu,Jing Zhao
标识
DOI:10.1186/s12951-022-01300-4
摘要
Ovarian cancer is the most lethal gynecological cancer which is characterized by extensive peritoneal implantation metastasis and malignant ascites. Despite advances in diagnosis and treatment in recent years, the five-year survival rate is only 25-30%. Therefore, developing multifunctional nanomedicine with abilities of promoting apoptosis and inhibiting migration on tumor cells would be a promising strategy to improve the antitumor effect.In this study, we developed a novel ACaT nanomedicine composed of alendronate, calcium ions and cyclin-dependent kinase 7 (CDK7) inhibitor THZ1. With the average size of 164 nm and zeta potential of 12.4 mV, the spherical ACaT nanoparticles were selectively internalized by tumor cells and effectively accumulated in the tumor site. Results of RNA-sequencing and in vitro experiments showed that ACaT promoted tumor cell apoptosis and inhibited tumor cell migration by arresting the cell cycle, increasing ROS and affecting calcium homeostasis. Weekly intraperitoneally administered of ACaT for 8 cycles significantly inhibited the growth of tumor and prolonged the survival of intraperitoneal xenograft mice.In summary, this study presents a new self-assembly nanomedicine with favorable tumor targeting, antitumor activity and good biocompatibility, providing a novel therapeutic strategy for advanced ovarian cancer.
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