Triple-Layered pH-Responsive Micelleplexes Loaded with siRNA and Cisplatin Prodrug for NF-Kappa B Targeted Treatment of Metastatic Breast Cancer
文献类型：期刊论文
| 作者 | Yu, Haijun1,2 ; Guo, Chengyue1,2,3; Feng, Bing1,2; Liu, Jianping1,2; Chen, Xianzhi1,2; Wang, Dangge1,2; Teng, Lesheng3; Li, Youxin3; Yin, Qi1,2; Zhang, Zhiwen1,2
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| 刊名 | THERANOSTICS
 |
| 出版日期 | 2016 |
| 卷号 | 6期号:1页码:14-27 |
| 关键词 | Cancer Metastasis Micelleplexes pH-Responsive RNAi Chemotherapy |
| ISSN号 | 1838-7640 |
| DOI | 10.7150/thno.13515 |
| 文献子类 | Article |
| 英文摘要 | The combination of chemotherapy and RNA interference is a promising approach for efficient cancer therapy. However, the success of such a strategy is hampered by the lack of suitable vectors to coordinate small interfering RNA (siRNA) and chemotherapeutic drug into one single platform. We herein report a novel triple-layered pH-responsive micelleplex loading siRNA and alkylated cisplatin prodrug for NF-Kappa B targeted treatment of metastatic breast cancer. The micelles were self-assembled from poly(ethylene glycol)-block-poly(aminolated glycidyl methacrylate)-block-poly(2-(diisopropyl amino) ethyl methacrylate) (PEG-b-PAGA-b-PDPA) triblock copolymers. At pH 7.4, the cisplatin prodrug was encapsulated in the hydrophobic PDPA core and siRNA was loaded on the positively charged PAGA interlayer to form the micelleplexes. The PEG corona can prevent protein absorption during blood circulation, minimize non-specific interaction with the reticuloendothelial system, and prolong the systemic circulation of the micelleplexes. The positively charged PAGA interlayer can facilitate deep tumor penetration of the micelleplexes, which, upon cellular uptake, are dissociated in the early endosomes to release anticancer drug payload due to protonation of the PDPA core. Using a 4T1 breast cancer model, we demonstrate that this novel micelleplex co-loaded with cisplatin prodrug and siRNA-p65 is able to simultaneously inhibit tumor growth and suppress distant metastasis of the cancer cells by downregulating NF-kappa B expression. The results reported in this study suggest that siRNA and anticancer drug co-delivery using pH-responsive micelleplexes is a promising strategy for efficient treatment of metastatic cancer. |
| WOS关键词 | EPITHELIAL-MESENCHYMAL TRANSITION ; CO-DELIVERY ; TUMOR-METASTASIS ; DRUG-DELIVERY ; DOXORUBICIN RESISTANCE ; POLYMERIC MICELLES ; ANTICANCER DRUGS ; NANOPARTICLES ; PENETRATION ; PACLITAXEL |
| 资助项目 | National Basic Research Program of China[2013CB932704] ; National Natural Science Foundation of China[81373359] ; National Natural Science Foundation of China[81270047] ; Youth Innovation Promotion Association CAS[00000000] |
| WOS研究方向 | Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:000363678500002 |
| 出版者 | IVYSPRING INT PUBL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276279]  |
| 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 | Yu, Haijun |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China; 3.Jilin Univ, Coll Life Sci, Changchun 130012, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yu, Haijun,Guo, Chengyue,Feng, Bing,et al. Triple-Layered pH-Responsive Micelleplexes Loaded with siRNA and Cisplatin Prodrug for NF-Kappa B Targeted Treatment of Metastatic Breast Cancer[J]. THERANOSTICS,2016,6(1):14-27. |
| APA | Yu, Haijun.,Guo, Chengyue.,Feng, Bing.,Liu, Jianping.,Chen, Xianzhi.,...&Li, Yaping.(2016).Triple-Layered pH-Responsive Micelleplexes Loaded with siRNA and Cisplatin Prodrug for NF-Kappa B Targeted Treatment of Metastatic Breast Cancer.THERANOSTICS,6(1),14-27. |
| MLA | Yu, Haijun,et al."Triple-Layered pH-Responsive Micelleplexes Loaded with siRNA and Cisplatin Prodrug for NF-Kappa B Targeted Treatment of Metastatic Breast Cancer".THERANOSTICS 6.1(2016):14-27. |
入库方式： OAI收割
来源：上海药物研究所
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