pH-Sensitive Nano-Complexes Overcome Drug Resistance and Inhibit Metastasis of Breast Cancer by Silencing Akt Expression
文献类型：期刊论文
| 作者 | Yin, Jieying1,2,3; Lang, Tianqun1,2,4; Cun, Dongmei3; Zheng, Zhong1,2; Huang, Yan1,2,3; Yin, Qi1,2 ; Yu, Haijun1,2; Li, Yaping1,2
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| 刊名 | THERANOSTICS
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| 出版日期 | 2017 |
| 卷号 | 7期号:17页码:4204-4216 |
| ISSN号 | 1838-7640 |
| DOI | 10.7150/thno.21516 |
| 文献子类 | Article |
| 英文摘要 | The therapy of breast cancer is encumbered by drug resistance and metastasis, which can be due to a defective PI3K/AKT/mTOR signaling pathway. This study was aimed at improving the anti-cancer effect of the chemotherapeutic agent paclitaxel (PTX) on the drug resistant and metastatic breast cancer by co-delivering PTX and a siRNA, siAkt, directed at silencing the Akt expression. Methods: The pH-sensitive amphiphilic polymer, poly [(1,4-butanediol)-diacrylate-beta-N, N-diisopropylethylenediamine]-polyethyleneimine (BDP) was synthesized. The PTX-loaded BDP micelle/siAkt nano-complex (PMA) was prepared and characterized. The cellular uptake, cytotoxicity, RNA interference efficiency, biodistribution, pharmacokinetics, pharmacodynamics, and biocompatibility of PMA in the murine metastatic breast cancer 4T1 cells and the 4T1 tumor-bearing mice were evaluated. Results: PMA was stable at the neutral as well as tumor extracellular pH and released the drugs in the intra-endo/lysosome acidic environment. In 4T1 cells, the RNA interference against the Akt gene down-regulated the expression of Akt and P-glycoprotein and up-regulated the expression of Caspase-3. The down-regulated P-gp inhibits the efflux of PTX thereby increasing its intracellular concentration, improving the cytotoxicity, and inhibiting the migration and invasion of 4T1 cells. In the 4T1 tumor-bearing mice, co-delivery of PTX and siAkt by PMA achieved a tumor inhibiting rate of 94.1% and suppressed 96.8% lung metastases. PMA did not cause pathological lesions in normal organs. Conclusion: PMA, by virtue of overcoming drug resistance and simultaneously restraining lung metastasis, might be an efficient drug delivery system for the therapy of breast cancer. |
| WOS关键词 | SIRNA DELIVERY ; TUMOR-METASTASIS ; THERAPY ; HETEROGENEITY ; THERAPEUTICS ; DESIGN |
| 资助项目 | National Basic Research Program of China[2014CB931900] ; National Natural Science Foundation of China[81690265] ; National Natural Science Foundation of China[81521005] ; Youth Innovation Promotion Association of CAS[2015226] |
| WOS研究方向 | Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:000412296800010 |
| 出版者 | IVYSPRING INT PUBL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275697]  |
| 专题 | 药物制剂研究中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Yin, Qi; Li, Yaping |
| 作者单位 | 1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Ctr Pharmaceut, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Liaoning, Peoples R China; 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yin, Jieying,Lang, Tianqun,Cun, Dongmei,et al. pH-Sensitive Nano-Complexes Overcome Drug Resistance and Inhibit Metastasis of Breast Cancer by Silencing Akt Expression[J]. THERANOSTICS,2017,7(17):4204-4216. |
| APA | Yin, Jieying.,Lang, Tianqun.,Cun, Dongmei.,Zheng, Zhong.,Huang, Yan.,...&Li, Yaping.(2017).pH-Sensitive Nano-Complexes Overcome Drug Resistance and Inhibit Metastasis of Breast Cancer by Silencing Akt Expression.THERANOSTICS,7(17),4204-4216. |
| MLA | Yin, Jieying,et al."pH-Sensitive Nano-Complexes Overcome Drug Resistance and Inhibit Metastasis of Breast Cancer by Silencing Akt Expression".THERANOSTICS 7.17(2017):4204-4216. |
入库方式： OAI收割
来源：上海药物研究所
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