Issue 41, 2016

Overcoming ABCG2-mediated multidrug resistance by a mineralized hyaluronan–drug nanocomplex

Abstract

Multidrug resistance (MDR), caused by the overexpression of ATP-binding cassette (ABC) transporters on the cell membrane, is a major obstacle in the chemotherapy of cancers. Among various transporters, ATP-binding cassette subfamily G member 2 (ABCG2) has garnered increasing attention as it has been proven to play a critical role in various cancer cells and even in many cancer stem cells. In this study, we developed a novel multicomponent nanocomplex by using a simple hyaluronan-based biomimetic mineralization reaction to simultaneously encapsulate a tyrosine kinase inhibitor (afatinib) as a non-traditional ABCG2 inhibitor and an anticancer drug (doxorubicin) as an apoptosis inducer. The resulting nanocomplex can achieve a highly synergistic effect to overcome ABCG2-mediated MDR by synchronously enhancing drug uptake and inhibiting drug efflux. It follows that a spatial–temporal synchronization of multiple components via a targeted biomimetic pathway would hold great promise for chemotherapy of ABCG2-mediated resistant cancers.

Graphical abstract: Overcoming ABCG2-mediated multidrug resistance by a mineralized hyaluronan–drug nanocomplex

Supplementary files

Article information

Article type
Paper
Submitted
22 Qas 2016
Accepted
17 Way 2016
First published
19 Way 2016

J. Mater. Chem. B, 2016,4, 6652-6661

Overcoming ABCG2-mediated multidrug resistance by a mineralized hyaluronan–drug nanocomplex

W. Chen, F. Wang, X. Zhang, J. Hu, X. Wang, K. Yang, L. Huang, M. Xu, Q. Li and L. Fu, J. Mater. Chem. B, 2016, 4, 6652 DOI: 10.1039/C6TB01545J

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