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Molecules 2016, 21(6), 720; doi:10.3390/molecules21060720

Poly (l-γ-glutamylglutamine) Polymer Enhances Doxorubicin Accumulation in Multidrug Resistant Breast Cancer Cells

1
Institute of Biomedical Engineering and Technology, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China
2
Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Didier Astruc
Received: 28 February 2016 / Revised: 22 May 2016 / Accepted: 27 May 2016 / Published: 2 June 2016
(This article belongs to the Collection Nanomedicine)
View Full-Text   |   Download PDF [2699 KB, uploaded 2 June 2016]   |  

Abstract

Background: Drug resistance is one of the bottlenecks of cancer chemotherapy in the clinic. Polymeric nanomedicine is one of the most promising strategies for overcoming poor chemotherapy responses due to the multidrug resistance (MDR). Methods: In this study, a new polymer-based drug delivery system, poly (l-γ-glutamylglutamine)-doxorubicin (PGG-Dox) conjugate, was studied in both drug-induced resistant human breast cancer MDA-MB-231/MDR cells and their parent human breast cancer MDA-MB-231 cells. The effect of PGG on facilitating the growth inhibition of Dox against multidrug resistant cells were investigated by evaluating the cytotoxicity of PGG-Dox conjugate, PGG/Dox unconjugated complex and free Dox on both cells. The underlying mechanisms in resistant cells were further studied via the intracellular traffic studies. Results: Both conjugated and unconjugated PGG significantly increased Dox uptake, prolonged Dox retention and reduced Dox efflux in the MDA-MB-231/MDR cells. The PGG-Dox conjugate is taken up by tumor cells mainly by pinocytosis pathway, in which PGG-Dox conjugate-containing vesicles are formed and enter the cells. Conclusions: This study indicated that both polymer-drug conjugate and unconjugated complex are promising strategies of overcoming resistance of anti-tumor drugs. View Full-Text
Keywords: multidrug resistance; PGG; doxorubicin; conjugate; polymer nanomedicines multidrug resistance; PGG; doxorubicin; conjugate; polymer nanomedicines
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Peng, T.; Liu, K.; Gao, L.; Gao, L.; Chen, J.; Wang, J.; Liu, Y.; Wang, Y.; Yan, Z.; Yu, L. Poly (l-γ-glutamylglutamine) Polymer Enhances Doxorubicin Accumulation in Multidrug Resistant Breast Cancer Cells. Molecules 2016, 21, 720.

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