The Seventh Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, 518107, Guangdong, People's Republic of China.
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen, 518107, Guangdong, People's Republic of China.
J Nanobiotechnology. 2022 Feb 22;20(1):93. doi: 10.1186/s12951-022-01300-4.
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.
卵巢癌是最致命的妇科癌症，其特征是广泛的腹膜种植转移和恶性腹水。尽管近年来在诊断和治疗方面取得了进展，但五年生存率仅为 25-30%。因此，开发具有促进肿瘤细胞凋亡和抑制迁移能力的多功能纳米医学是提高抗肿瘤效果的有前途的策略。
在这项研究中，我们开发了一种由阿仑膦酸钠、钙离子和细胞周期蛋白依赖性激酶 7 (CDK7) 抑制剂 THZ1 组成的新型 ACaT 纳米医学。ACaT 纳米球的平均粒径为 164nm，zeta 电位为 12.4mV，具有球形结构，可被肿瘤细胞选择性内化，并有效积聚在肿瘤部位。RNA 测序和体外实验结果表明，ACaT 通过细胞周期阻滞、增加 ROS 和影响钙稳态来促进肿瘤细胞凋亡和抑制肿瘤细胞迁移。每周腹腔内给予 ACaT 治疗 8 个周期，显著抑制肿瘤生长，延长腹腔异种移植小鼠的生存时间。
综上所述，本研究提出了一种具有良好肿瘤靶向性、抗肿瘤活性和良好生物相容性的新型自组装纳米医学，为晚期卵巢癌提供了一种新的治疗策略。
