Doxorubicin and Lapatinib Combination Nanomedicine for Treating Resistant Breast Cancer
文献类型：期刊论文
| 作者 | Wang, Huiyuan1 ; Li, Feng2; Du, Chengan2; Wang, Huixin1; Mahato, Ram I.3; Huang, Yongzhuo1
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| 刊名 | MOLECULAR PHARMACEUTICS
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| 出版日期 | 2014-08 |
| 卷号 | 11期号:8页码:2600-2611 |
| 关键词 | polymeric micelles breast cancer multidrug resistance combination therapy lapatinib doxorubicin nanomedicine |
| ISSN号 | 1543-8384 |
| DOI | 10.1021/mp400687w |
| 文献子类 | Article |
| 英文摘要 | Our objective was to design a polymeric micelle-based doxorubicin and lapatinib combination therapy for treating multidrug resistant (MDR) breast cancers. Poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonylpropylene carbonate) (PEG-PBC) polymers were synthesized for preparing doxorubicin and lapatinib loaded micelles using a film dispersion method. Micelles were characterized by determining critical micelle concentration (CMC), particle size distribution, and drug loading. The anticancer effects were determined in vitro with MTT assays as well as with lactate dehydrogenase (LDH) release studies. In addition, the cellular uptake of drug-loaded micelles was determined with fluorescence microscopy and flow cytometry. Finally, in vivo anticancer activity and tolerance of developed formulations were evaluated in resistant breast tumor bearing mice. PEG(5K)-PBC7K polymer synthesized in this study had a low CMC value (1.5 mg/L) indicating an excellent dynamic stability. PEG-PBC micelles could efficiently load both doxorubicin and lapatinib drugs with a loading density of 2196 and 8.4%, respectively. The mean particle size of these micelles was 100 nm and was not affected by drug loading. The use of lapatinib as an adjuvant sensitized drug resistant MCF-7/ADR cells to doxorubicin treatment. Cellular uptake studies showed enhanced doxorubicin accumulation in MCF-7/ADR cells in the presence of lapatinib. The doxorubicin and lapatinib combination therapy showed a significant decrease in tumor growth compared to doxorubicin monotherapy. In conclusion, we have developed PEG-PBC micelle formulations for the delivery of doxorubicin and lapatinib. The combination therapy of doxorubicin plus lapatinib has a great potential for treating MDR breast cancer. |
| WOS关键词 | REVERSES MULTIDRUG-RESISTANCE ; HYBRID NANOPARTICLE SYSTEM ; BLOCK-COPOLYMER MICELLES ; DRUG-DELIVERY ; P-GLYCOPROTEIN ; CELLS ; EFFLUX ; TRANSPORTERS ; ATP ; CHEMOTHERAPY |
| 资助项目 | National Basic Research Program of China (973 Program)[2013CB932503] ; National Basic Research Program of China (973 Program)[2014CB931900] ; NSFC, China[81172996] ; NSFC, China[81373357] ; Hampton University Faculty Research Award[00000000] ; Chinese Postdoctoral Science Foundation[2012M510097] ; Chinese Postdoctoral Science Foundation[2013T60478] ; Shanghai Pu-jiang Scholar Program[11PJ1411800] |
| WOS研究方向 | Research & Experimental Medicine ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000339982900010 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276968]  |
| 专题 | 药物制剂研究中心 |
| 通讯作者 | Li, Feng |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Hampton Univ, Sch Pharm, Dept Pharmaceut Sci, Hampton, VA 23668 USA; 3.Univ Nebraska Med Ctr, Dept Pharmaceut Sci, Omaha, NE 68198 USA |
| 推荐引用方式 GB/T 7714 | Wang, Huiyuan,Li, Feng,Du, Chengan,et al. Doxorubicin and Lapatinib Combination Nanomedicine for Treating Resistant Breast Cancer[J]. MOLECULAR PHARMACEUTICS,2014,11(8):2600-2611. |
| APA | Wang, Huiyuan,Li, Feng,Du, Chengan,Wang, Huixin,Mahato, Ram I.,&Huang, Yongzhuo.(2014).Doxorubicin and Lapatinib Combination Nanomedicine for Treating Resistant Breast Cancer.MOLECULAR PHARMACEUTICS,11(8),2600-2611. |
| MLA | Wang, Huiyuan,et al."Doxorubicin and Lapatinib Combination Nanomedicine for Treating Resistant Breast Cancer".MOLECULAR PHARMACEUTICS 11.8(2014):2600-2611. |
入库方式： OAI收割
来源：上海药物研究所
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