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Dual Drug-Loaded Reversible Core-Crosslinked nanocarrier with pH-Modulated Targeting and Redox-Controlled Drug Release for Overcoming Drug Resistance

Abstract

Herein, a pH and redox dual-sensitive core-crosslinked targeting nanocarrier was prepared and used for co-delivery of doxorubicin (DOX) and tariquidar (TQR). The nanocarrier not only owned an excellent stability but also prevented the leakage of drug in normal physiological environment efficiently. Meanwhile, the targeting function of nanocarriers could also be suppressed in normal physiological environment, protecting the nanocarriers from being captured by RAW264.7 cells. Under the mild acidic condition, the targeting function was regained, leading to an effective tumor cell uptake of the nanocarrier. Furthermore, reduction-responsive drug release would occur in cytoplasm due to the collapse of reduction-sensitive crosslinked structure in the nanocarrier. By means of the ligand-receptor mediated endocytosis and TQR-mediated P-glycoprotein (P-gp) inhibition, the IC50 value of DOX to MCF-7/ADR cells reduced from more than 100 μg/mL to 8.55 μg/mL, exhibiting a great potential in overcoming drug resistance.

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Publication details

The article was received on 05 Jun 2017, accepted on 29 Sep 2017 and first published on 02 Oct 2017


Article type: Paper
DOI: 10.1039/C7TB01504F
Citation: J. Mater. Chem. B, 2017, Accepted Manuscript
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    Dual Drug-Loaded Reversible Core-Crosslinked nanocarrier with pH-Modulated Targeting and Redox-Controlled Drug Release for Overcoming Drug Resistance

    D. zhao, S. Ma, X. Yi, S. Cheng, R. Zhuo and F. Li, J. Mater. Chem. B, 2017, Accepted Manuscript , DOI: 10.1039/C7TB01504F

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