Triple negative breast cancer therapy with CDK1 siRNA delivered by cationic lipid assisted PEG-PLA nanoparticles

被引:88
|
作者
Liu, Yang [1 ,2 ]
Zhu, Yan-Hua [1 ,2 ]
Mao, Cheng-Qiong [1 ,2 ]
Dou, Shuang [1 ,2 ,3 ]
Shen, Song [1 ,2 ]
Tan, Zi-Bin [1 ,2 ]
Wang, Jun [1 ,2 ,3 ,4 ]
机构
[1] Univ Sci & Technol China, Sch Life Sci, CAS Key Lab Innate Immun & Chron Dis, Hefei 230027, Anhui, Peoples R China
[2] Univ Sci & Technol China, Med Ctr, Hefei 230027, Anhui, Peoples R China
[3] Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China
[4] Univ Sci & Technol China, CAS, High Field Magnet Lab, Hefei 230026, Anhui, Peoples R China
基金
国家高技术研究发展计划(863计划); 中国国家自然科学基金;
关键词
Triple-negative breast cancer; Synthetic lethality; siRNA delivery; Cationic lipid assisted nanoparticle; Cyclin-dependent kinase 1; SYNTHETIC LETHAL INTERACTION; C-MYC; INHIBITION; ACTIVATION; COMPLEX; POLY(ADP-RIBOSE); PROGRESSION; PATHWAYS; PROTEIN; TUMORS;
D O I
10.1016/j.jconrel.2014.07.001
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
There is no effective clinical therapy yet for triple-negative breast cancer (TNBC) without particular human epidermal growth factor receptor-2, estrogen and progesterone receptor expression. In this study, we report a molecularly targeted and synthetic lethality-based siRNA therapy for TNBC treatment, using cationic lipid assisted poly(ethylene glycol)-b-poly(D, L-lactide) (PEG-PLA) nanoparticles as the siRNA carrier. It is demonstrated that only in c-Myc overexpressed TNBC cells, while not in normal mammary epithelial cells, delivery of siRNA targeting cyclin-dependent kinase 1 (CDK1) with the nanoparticle carrier (NPsiCDK1) induces cell viability decreasing and cell apoptosis through RNAi-mediated CDK1 expression inhibition, indicating the synthetic lethality between c-Myc with CDK1 in TNBC cells. Moreover, systemic delivery of NPsiCDK1 is able to suppress tumor growth in mice bearing SUM149 and BT549 xenograft and cause no systemic toxicity or activate the innate immune response, suggesting the therapeutic promise with such nanoparticles carrying siCDK1 for c-Myc overexpressed triple negative breast cancer. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:114 / 121
页数:8
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