|The co-delivery of a low-dose P-glycoprotein inhibitor with doxorubicin sterically stabilized liposomes against breast cancer with low P-glycoprotein expression|
|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|
|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|
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.
|项目编号||81130059 ; 2009CB930300 ; BMU20110263|
|资助机构||National Science Foundation of China ; National Research Fund for Fundamental Key Project ; Innovation Team of the Ministry of Education|
|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
|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.|
|APA||Gao, Wei.,Lin, Zhiqiang.,Chen, Meiwan.,Yang, Xiucong.,Cui, Zheng.,...&Zhang, Qiang.(2014).The co-delivery of a low-dose P-glycoprotein inhibitor with doxorubicin sterically stabilized liposomes against breast cancer with low P-glycoprotein expression.INTERNATIONAL JOURNAL OF NANOMEDICINE,9,3425-3437.|
|MLA||Gao, Wei,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".INTERNATIONAL JOURNAL OF NANOMEDICINE 9(2014):3425-3437.|