Improving penetration in tumors with nanoassemblies of phospholipids and doxorubicin
文献类型：期刊论文
| 作者 | Tang, Ning; Du, Gangjun; Wang, Nan; Liu, Chunchun; Hang, Haiying; Liang, Wei |
| 刊名 | JOURNAL OF THE NATIONAL CANCER INSTITUTE
 |
| 出版日期 | 2007-07-04 |
| 卷号 | 99期号:13页码:1004-1015 |
| ISSN号 | 0027-8874 |
| DOI | 10.1093/jnci/djm027 |
| 文献子类 | Article |
| 英文摘要 | Background Drug delivery and penetration into neoplastic cells distant from tumor vessels is critical for the effectiveness of solid tumor chemotherapy. We hypothesized that 10- to 20-nm nanoassemblies of phospholipids containing doxorubicin would improve the drug's penetration, accumulation, and antitumor activity. Methods Doxorubicin was incorporated into polyethylene glycol-phosphatidylethanolamine (PEG-PE) block copolymer micelles by a self-assembly procedure to form nanoassemblies of doxorubicin and PEG-PE. In vitro cytotoxicity of micelle-encapsulated doxorubicin (M-Dox) against A549 human non-small-cell lung carcinoma cells was examined using the methylthiazoletetrazolium assay, and confocal microscopy, total internal reflection fluorescence microscopy, and flow cytometry were used to examine intracellular distribution and the cellular uptake mechanism. C57B1/6 mice (n = 10-40 per group) bearing subcutaneous or pulmonary Lewis lung carcinoma (LLC) tumors were treated with M-Dox or free doxorubicin, and tumor growth, doxorubicin pharmacokinetics, and mortality were compared. Toxicity was analyzed in tumor-free mice. All statistical tests were two-sided. Results Encapsulation of doxorubicin in PEG-PE micelles increased its internalization by A549 cells into lysosomes and enhanced cytotoxicity. Drug-encapsulated doxorubicin was more effective in inhibiting tumor growth in the subcutaneous LLC tumor model (mean tumor volumes in mice treated with 5 mg/kg M-Dox = 1126 mm(3) and in control mice = 3693 mm(3), difference = 2567 mm(3), 95% confidence interval [CI] = 2190 to 2943 mm(3), P <.001) than free doxorubicin (mean tumor volumes in doxorubicin-treated mice = 3021 mm(3) and in control mice = 3693 mm(3), difference = 672 mm(3), 95% Cl = 296 to 1049 mm(3), P = .0332, Wilcoxon signed rank test). M-Dox treatment prolonged survival in both mouse models and reduced metastases in the pulmonary model; it also reduced toxicity. Conclusions We have developed a novel PEG-PE-based nanocarrier of doxorubicin that increased cytotoxicity in vitro and enhanced antitumor activity in vivo with low systemic toxicity. This drug packaging technology may provide a new strategy for design of cancer therapies. |
| WOS关键词 | SOLID TUMORS ; PHASE-I ; LIPOSOMAL DOXORUBICIN ; VASCULAR-PERMEABILITY ; ANTITUMOR-ACTIVITY ; DRUG PENETRATION ; BREAST-CANCER ; BLOOD-VESSELS ; CARRIERS ; CELLS |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000248118900008 |
| 出版者 | OXFORD UNIV PRESS INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273204]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Liang, Wei |
| 作者单位 | 1.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Protein & Peptide Pharmaceut Lab, Beijing 100101, Peoples R China 2.Chinese Acad Sci, Inst Biophys, Ctr Infect & Immun, Beijing 100101, Peoples R China 3.Chinese Acad Sci, Inst Mat Med, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Tang, Ning,Du, Gangjun,Wang, Nan,et al. Improving penetration in tumors with nanoassemblies of phospholipids and doxorubicin[J]. JOURNAL OF THE NATIONAL CANCER INSTITUTE,2007,99(13):1004-1015. |
| APA | Tang, Ning,Du, Gangjun,Wang, Nan,Liu, Chunchun,Hang, Haiying,&Liang, Wei.(2007).Improving penetration in tumors with nanoassemblies of phospholipids and doxorubicin.JOURNAL OF THE NATIONAL CANCER INSTITUTE,99(13),1004-1015. |
| MLA | Tang, Ning,et al."Improving penetration in tumors with nanoassemblies of phospholipids and doxorubicin".JOURNAL OF THE NATIONAL CANCER INSTITUTE 99.13(2007):1004-1015. |
入库方式： OAI收割
来源：上海药物研究所
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