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The co-delivery of a low-dose P-glycoprotein inhibitor with doxorubicin sterically stabilized liposomes against breast cancer with low P-glycoprotein expression
Gao W.1; Lin Z.1; Chen M.2; Yang X.1; Cui Z.1; Zhang X.1; Yuan L.1; Zhang Q.1
2014-07-21
Source PublicationInternational Journal of Nanomedicine
ISSN11782013 11769114
Volume9Issue:1Pages:3425-3437
AbstractIntroduction: 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. © 2014 Gao et al.
KeywordAntitumor activity Cyclosporine A Liposomes Low-P-gp-expressing tumor Targeted delivery
DOI10.2147/IJN.S56070
URLView the original
Language英語
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Cited Times [WOS]:8   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Peking University
2.Universidade de Macau
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GB/T 7714
Gao W.,Lin Z.,Chen M.,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(1):3425-3437.
APA Gao W..,Lin Z..,Chen M..,Yang X..,Cui Z..,...&Zhang Q..(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(1),3425-3437.
MLA Gao W.,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 9.1(2014):3425-3437.
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