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学科主题: 药学
题名:
The co-delivery of a low-dose P-glycoprotein inhibitor with doxorubicin sterically stabilized liposomes against breast cancer with low P-glycoprotein expression
作者: Gao, Wei1; Lin, Zhiqiang1; Chen, Meiwan2; Yang, Xiucong1; Cui, Zheng1; Zhang, Xiaofei1; Yuan, Lan3; Zhang, Qiang1
关键词: liposomes ; low-P-gp-expressing tumor ; antitumor activity ; cyclosporine A ; targeted delivery
刊名: INTERNATIONAL JOURNAL OF NANOMEDICINE
发表日期: 2014
DOI: 10.2147/IJN.S56070
卷: 9, 页:3425-3437
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Nanoscience & Nanotechnology ; Pharmacology & Pharmacy
研究领域[WOS]: Science & Technology - Other Topics ; Pharmacology & Pharmacy
关键词[WOS]: MULTIDRUG-RESISTANCE GENE ; CYCLOSPORINE-A ; MCF-7/ADR CELLS ; DRUG-DELIVERY ; TUMOR-CELLS ; SDZ PSC-833 ; IN-VITRO ; ENCAPSULATION ; MODULATION ; EFFICIENT
英文摘要:

Introduction: P-glycoprotein (P-gp) inhibitors are usually used to treat tumors that overexpress P-gps. However, most common types of breast cancers, such as Luminal A, are low-P-gp expressing, at least during the initial phases of treatment. Therefore, it would be interesting to know if P-gp inhibitors are still useful in treating low-P-gp-expressing tumors.

Methods: In the study reported here, the human breast-cancer cell line MCF-7, chosen as a model of Luminal A, was found to be low-P-gp expressing. We designed a novel doxorubicin (DOX) sterically stabilized liposome system co-loaded with the low-dose P-gp inhibitor cyclosporine A (CsA) (DOX/CsA/SSL).

Results: The co-delivery system showed good size uniformity, high encapsulation efficiency, and a desirable release profile. The cell-uptake and cytotoxicity studies demonstrated that CsA could significantly enhance the intracellular accumulation and toxicity of free DOX and the liposomal DOX in MCF-7 cells. The confocal microscopy and in vivo imaging study confirmed the intracellular and in vivo targeting effect of DOX/CsA/SSL, respectively. Finally, the in vivo study proved that DOX/CsA/SSL could achieve significantly better antitumor effect against MCF-7 tumor than controls, without inducing obvious systemic toxicity.

Conclusion: This study demonstrated that the co-delivery of a low-dose P-gp inhibitor and liposomal DOX could improve the therapy of low-P-gp-expressing cancer, which is of significance in clinical tumor therapy.

语种: 英语
所属项目编号: 81130059 ; 2009CB930300 ; BMU20110263
项目资助者: National Science Foundation of China ; National Research Fund for Fundamental Key Project ; Innovation Team of the Ministry of Education
WOS记录号: WOS:000339818100001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64718
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macao, Peoples R China
3.Peking Univ, Med & Hlth Analyt Ctr, Beijing 100191, Peoples R China

Recommended Citation:
Gao, Wei,Lin, Zhiqiang,Chen, Meiwan,et al. The co-delivery of a low-dose P-glycoprotein inhibitor with doxorubicin sterically stabilized liposomes against breast cancer with low P-glycoprotein expression[J]. INTERNATIONAL JOURNAL OF NANOMEDICINE,2014,9:3425-3437.
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