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Smart pH-Sensitive and Temporal-Controlled Polymeric Micelles for Effective Combination Therapy of Doxorubicin and Disulfiram
文献类型：期刊论文
| 作者 | Duan, Xiaopin1,2; Xiao, Jisheng1; Yin, Qi1 ; Zhang, Zhiwen1; Yu, Haijun1; Mao, Shirui2; Li, Yaping1
|
| 刊名 | ACS NANO
 |
| 出版日期 | 2013-07 |
| 卷号 | 7期号:7页码:5858-5869 |
| 关键词 | combination therapy multidrug resistance pH-sensitive polymeric micelles doxorubicin disulfiram temporal release |
| ISSN号 | 1936-0851 |
| DOI | 10.1021/nn4010796 |
| 文献子类 | Article |
| 英文摘要 | The combination of a chemotherapeutic drug with a multidrug resistance (MDR) modulator has emerged as a promising strategy for treating MDR cancer. To ensure two drugs could be simultaneously delivered to tumor region at the optimum ratio, and the MDR modulator could be released earlier and faster than the chemotherapeutic drug to inactivate P-glycoprotein (Pip) and subsequently inhibit the pumping out of the chemotherapeutic drug, a smart pH-sensitive polymeric micelles system with high drug loading and precise drug ratio was designed and prepared by conjugating doxorubicin (DOX) to poly(styrene-co-maleic anhydride) (SMA) derivative with adipic dihydrazide (ADH) through a add-cleavable hydrazone bond, and then encapsulating disulfiram (DSF), a P-gp inhibitor as well as an apoptosis inducer, into the micelles formed by the self-assembly of SMA-ADH-DOX (SAD) conjugate. The pH-sensitive polymeric micelles system enabled a temporal release of two drugs: encapsulated DSF was released fast to inhibit the activity of P-gp and restore cell apoptotic signaling pathways, while conjugated DOX was released in a sustained and pH-dependent manner and highly accumulated in drug resistant cells to exert therapeutic effect, due to the inactivation of Pip by DSF. The smart co-delivery system was very effective in enhancing the cytotoxicity by increasing the intracellular accumulation of DOX and promoting the apoptotic response, and showed the most effective inhibitory effect on the growth of drug-resistant breast cancer xenografts as compared to other combinations of both drugs. In a word, this smart co-delivery system has significant promise for the clinical therapy of MDR cancer. |
| WOS关键词 | CANCER CELL-LINES ; KAPPA-B ACTIVITY ; BREAST-CANCER ; DRUG-RESISTANCE ; FLIP-FLOP ; MULTIDRUG-RESISTANCE ; ANTIALCOHOLISM DRUG ; PROTEASOME ACTIVITY ; NANOPARTICLES ; INHIBITION |
| 资助项目 | National Basic Research Program of China[2010CB934000] ; National Basic Research Program of China[2013CB932704] ; National Basic Research Program of China[2013CB932503] ; National Natural Science Foundation of China[30925041] ; National Natural Science Foundation of China[81230029] ; Shanghai Program[11 nm0505900] |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000322417400026 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277549]  |
| 专题 | 药物制剂研究中心 |
| 通讯作者 | Li, Yaping |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China; 2.Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Peoples R China |
| 推荐引用方式 GB/T 7714 | Duan, Xiaopin,Xiao, Jisheng,Yin, Qi,et al. Smart pH-Sensitive and Temporal-Controlled Polymeric Micelles for Effective Combination Therapy of Doxorubicin and Disulfiram[J]. ACS NANO,2013,7(7):5858-5869. |
| APA | Duan, Xiaopin.,Xiao, Jisheng.,Yin, Qi.,Zhang, Zhiwen.,Yu, Haijun.,...&Li, Yaping.(2013).Smart pH-Sensitive and Temporal-Controlled Polymeric Micelles for Effective Combination Therapy of Doxorubicin and Disulfiram.ACS NANO,7(7),5858-5869. |
| MLA | Duan, Xiaopin,et al."Smart pH-Sensitive and Temporal-Controlled Polymeric Micelles for Effective Combination Therapy of Doxorubicin and Disulfiram".ACS NANO 7.7(2013):5858-5869. |
入库方式： OAI收割
来源：上海药物研究所
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