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Nanomaterials 2015, 5(4), 1571-1587; doi:10.3390/nano5041571

Preparation of GST Inhibitor Nanoparticle Drug Delivery System and Its Reversal Effect on the Multidrug Resistance in Oral Carcinoma

1
School of Pharmaceutical Sciences, Jilin University, No.1266 Fujin Road, Changchun 130012, China
2
Changchun Women and Children Health Hospital, No. 962 Xinfa Road, Changchun 130061, China
3
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, No.103 Wenhua Road, Shenyang 110016, China
4
China Japan Union Hospital, Jilin University, No. 126 Xiantai Street, Changchun 130033, China
*
Author to whom correspondence should be addressed.
Academic Editor: Luigi Pasqua
Received: 25 August 2015 / Revised: 23 September 2015 / Accepted: 24 September 2015 / Published: 29 September 2015
(This article belongs to the Special Issue Nanomaterials for Cancer Therapies)
View Full-Text   |   Download PDF [1928 KB, uploaded 29 September 2015]   |  

Abstract

During the chemotherapy of cancer, drug resistance is the first issue that chemotherapeutic drugs cannot be effectively used for the treatment of cancers repeatedly for a long term, and the main reason for this is that tumor cell detoxification is mediated by GSH (glutathione) catalyzed by GST (glutathione-S-transferase). In this study, a GST inhibitor, ethacrynic acid (ECA), was designed to be coupled with methoxy poly(ethylene glycol)-poly(lactide) (MPEG–PLA) by disulfide bonds to prepare methoxy poly(ethylene glycol)-poly(lactide)-disulphide bond-mthacrynic acid (MPEG–PLA–SS–ECA) as a carrier material of the nanoparticles. Nanoparticles of pingyangmycin (PYM) and carboplatin (CBP) were prepared, respectively, and their physicochemical properties were investigated. The ECA at the disulfide could be released in the presence of GSH, the pingyangmycin, carboplatin and ECA were all uniformly released, and the nanoparticles could release all the drugs completely within 10 days. The half maximal inhibitory concentration (IC50) of the prepared MPEG–PLA–SS–ECA/CBP and MPEG–PLA–SS–ECA/PYM nanoparticles in drug-resistant oral squamous cell carcinoma cell lines SCC15/CBP and SCC15/PYM cells was 12.68 μg·mL1 and 12.76 μg·mL1, respectively; the resistant factor RF of them in the drug-resistant cells were 1.51 and 1.24, respectively, indicating that MPEG–PLA–SS–ECA nanoparticles can reverse the drug resistance of these two drug-resistant cells. View Full-Text
Keywords: nanoparticle; GST inhibitor; redox-sensitive; self-assembly nanoparticle; GST inhibitor; redox-sensitive; self-assembly
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Han, B.; Wang, Y.; Wang, L.; Shang, Z.; Wang, S.; Pei, J. Preparation of GST Inhibitor Nanoparticle Drug Delivery System and Its Reversal Effect on the Multidrug Resistance in Oral Carcinoma. Nanomaterials 2015, 5, 1571-1587.

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