Codelivery of dihydroartemisinin and doxorubicin in mannosylated liposomes for drug-resistant colon cancer therapy
文献类型：期刊论文
| 作者 | Kang, Xue-jia1,2; Wang, Hui-yuan2 ; Peng, Hui-ge2; Chen, Bin-fan2; Zhang, Wen-yuan2; Wu, Ai-hua1,2; Xu, Qin1; Huang, Yong-zhuo2
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2017-06 |
| 卷号 | 38期号:6页码:885-896 |
| 关键词 | human colon cancer multidrug resistance doxorubicin dihydroartemisinin combination therapy tumor-targeted delivery mannosylated liposome mannose receptor |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2017.10 |
| 文献子类 | Article |
| 英文摘要 | Multidrug resistance (MDR) is a major hurdle in cancer chemotherapy and makes the treatment benefits unsustainable. Combination therapy is a commonly used method for overcoming MDR. In this study we investigated the anti-MDR effect of dihydroartemisinin (DHA), a derivative of artemisinin, in combination with doxorubicin (Dox) in drug-resistant human colon tumor HCT8/ADR cells. We developed a tumor-targeting codelivery system, in which the two drugs were co-encapsulated into the mannosylated liposomes (Manliposomes). The Man-liposomes had a mean diameter of 158.8 nm and zeta potential of -15.8 mV. In the HCT8/ADR cells that overexpress the mannose receptors, the Man-liposomes altered the intracellular distribution of Dox, resulting in a high accumulation of Dox in the nuclei and thus displaying the highest cytotoxicity (IC50=0.073 mu g/mL) among all the groups. In a subcutaneous HCT8/ADR tumor xenograft model, administration of the Man-liposomes resulted in a tumor inhibition rate of 88.59%, compared to that of 47.46% or 70.54%, respectively, for the treatment with free Dox or free Dox+ DHA. The mechanisms underlying the anti-MDR effect of the Manliposomes involved preferential nuclear accumulation of the therapeutic agents, enhanced cancer cell apoptosis, downregulation of Bcl-xl, and the induction of autophagy. |
| WOS关键词 | BREAST-CANCER ; CELLS ; AUTOPHAGY ; APOPTOSIS ; MECHANISMS ; STRATEGIES ; MORTALITY |
| 资助项目 | 973 Program, China[2014CB931900] ; 973 Program, China[2013CB932503] ; National Natural Science Foundation of China[81373357] ; National Natural Science Foundation of China[81422048] ; National Natural Science Foundation of China[81402883] ; National Natural Science Foundation of China[81521005] ; National Natural Science Foundation of China[81673382] ; Scientific Research and Equipment Development Project, Chinese Academy of Sciences[YZ201437] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:5998008 |
| WOS记录号 | WOS:000402526900013 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272646]  |
| 专题 | 药物制剂研究中心 |
| 通讯作者 | Xu, Qin; Huang, Yong-zhuo |
| 作者单位 | 1.Guangzhou Univ Chinese Med, Inst Trop Med, Guangzhou 510405, Guangdong, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Kang, Xue-jia,Wang, Hui-yuan,Peng, Hui-ge,et al. Codelivery of dihydroartemisinin and doxorubicin in mannosylated liposomes for drug-resistant colon cancer therapy[J]. ACTA PHARMACOLOGICA SINICA,2017,38(6):885-896. |
| APA | Kang, Xue-jia.,Wang, Hui-yuan.,Peng, Hui-ge.,Chen, Bin-fan.,Zhang, Wen-yuan.,...&Huang, Yong-zhuo.(2017).Codelivery of dihydroartemisinin and doxorubicin in mannosylated liposomes for drug-resistant colon cancer therapy.ACTA PHARMACOLOGICA SINICA,38(6),885-896. |
| MLA | Kang, Xue-jia,et al."Codelivery of dihydroartemisinin and doxorubicin in mannosylated liposomes for drug-resistant colon cancer therapy".ACTA PHARMACOLOGICA SINICA 38.6(2017):885-896. |
入库方式： OAI收割
来源：上海药物研究所
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