Targeted Nanoassembly Loaded with Docetaxel Improves Intracellular Drug Delivery and Efficacy in Murine Breast Cancer Model
文献类型：期刊论文
| 作者 | Gao, Yu; Chen, Lingli ; Gu, Wangwen; Xi, Yong; Lin, Liping; Li, Yaping
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| 刊名 | MOLECULAR PHARMACEUTICS
 |
| 出版日期 | 2008-11 |
| 卷号 | 5期号:6页码:1044-1054 |
| 关键词 | Breast cancer docetaxel nanoassembly epidermal growth factor |
| ISSN号 | 1543-8384 |
| DOI | 10.1021/mp800072e |
| 文献子类 | Article |
| 英文摘要 | Docetaxel is one of the most promising chemotherapeutic agents for the treatment of metastatic breast cancer, but it shows tearful side effects. We hypothesized that a novel targeted nanoassembly (TNA) could provide efficient intracellular drug delivery in breast tumor cells overexpressing epidermal growth factor (EGF) receptor and thus improve the efficacy and reduce the side effects of docetaxel. We prepared the novel docetaxel loaded TNAs formed by polyethylene glycol-distearoylphosphatidylethanolamine (PEG-DSPE) and modified with EGF. Compared with nontargeted nanoassemblies (NNAs), TNAs showed obvious improvement of cell-specific uptake and internalization, and revealed more cytotoxicity against MDA-MB-468 cells by inducing more late apoptosis and subG1 cells at low drug concentration, or more G2/M arrest at high drug concentration than NNAs or Taxotere. In BALB/c mice bearing breast tumor xenografts, TNAs showed stronger inhibition of tumor growth compared with NNAs (relative tumor volume in mice treated with 5 mg/kg TNAs = 0.99 and 10 mg/kg NNAs = 1.71, p < 0.05) or Taxotere (relative tumor volume in mice treated with 5 mg/kg TNAs = 0.99 and 10 mg/kg Taxotere = 4.20, p < 0.01). In particular, tumor disappeared completely in the TNA group at a dose of 10 mg/kg. The maximum tolerated dose (MTD) of TNAs was about four times higher than that of Taxotere. TNAs also demonstrated a much longer circulation time in vivo and more drug accumulation in tumor in a murine breast cancer model than Taxotere. TNA treatment also prolonged survival of mice. These results suggested that TNAs could have more potential as a delivery system for breast cancer chemotherapy. |
| WOS关键词 | POORLY SOLUBLE DRUGS ; IN-VITRO ; DIACYLLIPID MICELLES ; POLYMERIC MICELLES ; ANTICANCER DRUGS ; TUMOR-CELLS ; CARRIERS ; THERAPY ; NANOPARTICLES ; AGENTS |
| 资助项目 | National Basic Research Program of China[2007CB935804] ; National Basic Research Program of China[2006CB933304] ; National Natural Science Foundation of China[30572259] ; Important Direction Program of CAS[KJCX2.YW.M02] |
| WOS研究方向 | Research & Experimental Medicine ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000261320800014 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272768]  |
| 专题 | 药物制剂研究中心 上海中药现代化研究中心 |
| 通讯作者 | Li, Yaping |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gao, Yu,Chen, Lingli,Gu, Wangwen,et al. Targeted Nanoassembly Loaded with Docetaxel Improves Intracellular Drug Delivery and Efficacy in Murine Breast Cancer Model[J]. MOLECULAR PHARMACEUTICS,2008,5(6):1044-1054. |
| APA | Gao, Yu,Chen, Lingli,Gu, Wangwen,Xi, Yong,Lin, Liping,&Li, Yaping.(2008).Targeted Nanoassembly Loaded with Docetaxel Improves Intracellular Drug Delivery and Efficacy in Murine Breast Cancer Model.MOLECULAR PHARMACEUTICS,5(6),1044-1054. |
| MLA | Gao, Yu,et al."Targeted Nanoassembly Loaded with Docetaxel Improves Intracellular Drug Delivery and Efficacy in Murine Breast Cancer Model".MOLECULAR PHARMACEUTICS 5.6(2008):1044-1054. |
入库方式： OAI收割
来源：上海药物研究所
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