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Preparation of GST Inhibitor Nanoparticle Drug Delivery System and Its Reversal Effect on the Multidrug Resistance in Oral Carcinoma
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 (glut...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5304786/ https://www.ncbi.nlm.nih.gov/pubmed/28347082 http://dx.doi.org/10.3390/nano5041571 |
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author | Han, Bing Wang, Yanli Wang, Lan Shang, Zuhui Wang, Shuang Pei, Jin |
author_facet | Han, Bing Wang, Yanli Wang, Lan Shang, Zuhui Wang, Shuang Pei, Jin |
author_sort | Han, Bing |
collection | PubMed |
description | 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 (IC(50)) 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·mL(−1) and 12.76 μg·mL(−1), 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. |
format | Online Article Text |
id | pubmed-5304786 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-53047862017-03-21 Preparation of GST Inhibitor Nanoparticle Drug Delivery System and Its Reversal Effect on the Multidrug Resistance in Oral Carcinoma Han, Bing Wang, Yanli Wang, Lan Shang, Zuhui Wang, Shuang Pei, Jin Nanomaterials (Basel) Article 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 (IC(50)) 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·mL(−1) and 12.76 μg·mL(−1), 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. MDPI 2015-09-29 /pmc/articles/PMC5304786/ /pubmed/28347082 http://dx.doi.org/10.3390/nano5041571 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Han, Bing Wang, Yanli Wang, Lan Shang, Zuhui Wang, Shuang Pei, Jin Preparation of GST Inhibitor Nanoparticle Drug Delivery System and Its Reversal Effect on the Multidrug Resistance in Oral Carcinoma |
title | Preparation of GST Inhibitor Nanoparticle Drug Delivery System and Its Reversal Effect on the Multidrug Resistance in Oral Carcinoma |
title_full | Preparation of GST Inhibitor Nanoparticle Drug Delivery System and Its Reversal Effect on the Multidrug Resistance in Oral Carcinoma |
title_fullStr | Preparation of GST Inhibitor Nanoparticle Drug Delivery System and Its Reversal Effect on the Multidrug Resistance in Oral Carcinoma |
title_full_unstemmed | Preparation of GST Inhibitor Nanoparticle Drug Delivery System and Its Reversal Effect on the Multidrug Resistance in Oral Carcinoma |
title_short | Preparation of GST Inhibitor Nanoparticle Drug Delivery System and Its Reversal Effect on the Multidrug Resistance in Oral Carcinoma |
title_sort | preparation of gst inhibitor nanoparticle drug delivery system and its reversal effect on the multidrug resistance in oral carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5304786/ https://www.ncbi.nlm.nih.gov/pubmed/28347082 http://dx.doi.org/10.3390/nano5041571 |
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