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Enhanced activity of doxorubicin in drug resistant A549 tumor cells by encapsulation of P‑glycoprotein inhibitor in PLGA‑based nanovectors

  • Authors:
    • Liang Xu
    • Hua Li
    • Yubin Wang
    • Fang Dong
    • Huangbing Wang
    • Shutong Zhang

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  • Published online on: November 27, 2013     https://doi.org/10.3892/ol.2013.1711
  • Pages: 387-392
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Abstract

Effective chemotherapy remains an important issue in the treatment of drug resistant cancer. The aim of the present study was to establish novel polymeric nanoparticles composed of the antitumor drug, doxorubicin (DOX), and an inhibitor of the drug efflux pump‑associated protein, P‑glycoprotein (P‑gp), in order to overcome drug resistance in tumor cells. Poly(D,L‑lactide‑co‑glycolide) (PLGA), DOX‑loaded PLGA (PLGA‑DOX), P‑gp inhibitor (cyclosporin A; CsA)‑coated PLGA (PLGA‑CsA) and DOX and CsA co‑loaded PLGA (PLGA‑DOX‑CsA) nanoparticles were prepared using solvent evaporation. The size distribution, ζ potential and electron microscopy observations of the nanoparticles were characterized. Accumulation and efflux assays were performed using confocal and fluorescence‑activated cell sorting (FACS), and the pump activity of P‑gp was detected through FACS. The uptake of the nanoparticles and the viability of Taxol‑resistant A549 cells treated with various nanoparticles were analyzed via FACS in vitro. Furthermore, the tumor growth and survival rates of A549‑Taxol‑bearing mice were monitored in vivo. Prepared particles were nanosized and the efflux rates of PLGA‑DOX and PLGA‑DOX‑CsA were significantly decreased compared with the free DOX. Drug efflux pump activity was effectively inhibited by the PLGA‑CsA and PLGA‑DOX‑CsA groups compared with the PLGA, PLGA‑DOX and free DOX groups. Cell viability results demonstrated that PLGA‑DOX and PLGA‑DOX‑CsA induced the increased death of A549‑Taxol cells. In vivo tumor models demonstrated that PLGA‑DOX and PLGA‑DOX‑CsA markedly inhibited the tumor growth and improved the survival rate of A549‑Taxol‑bearing mice. Antitumor drug and drug efflux pump inhibitor co‑loaded nanoparticles offer advantages to overcome the drug resistance of tumors and highlight new therapeutic strategies to control drug resistant tumors.
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2014-February
Volume 7 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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  • Impact Factor: 2.5
  • Ranked Oncology
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  • CiteScore: 5.7
  • CiteScore Rank: Q2: #139/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.574
  • SCImago Journal Rank (SJR): 0.644
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Spandidos Publications style
Xu L, Li H, Wang Y, Dong F, Wang H and Zhang S: Enhanced activity of doxorubicin in drug resistant A549 tumor cells by encapsulation of P‑glycoprotein inhibitor in PLGA‑based nanovectors. Oncol Lett 7: 387-392, 2014.
APA
Xu, L., Li, H., Wang, Y., Dong, F., Wang, H., & Zhang, S. (2014). Enhanced activity of doxorubicin in drug resistant A549 tumor cells by encapsulation of P‑glycoprotein inhibitor in PLGA‑based nanovectors. Oncology Letters, 7, 387-392. https://doi.org/10.3892/ol.2013.1711
MLA
Xu, L., Li, H., Wang, Y., Dong, F., Wang, H., Zhang, S."Enhanced activity of doxorubicin in drug resistant A549 tumor cells by encapsulation of P‑glycoprotein inhibitor in PLGA‑based nanovectors". Oncology Letters 7.2 (2014): 387-392.
Chicago
Xu, L., Li, H., Wang, Y., Dong, F., Wang, H., Zhang, S."Enhanced activity of doxorubicin in drug resistant A549 tumor cells by encapsulation of P‑glycoprotein inhibitor in PLGA‑based nanovectors". Oncology Letters 7, no. 2 (2014): 387-392. https://doi.org/10.3892/ol.2013.1711