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Novel pH-sensitive nanoformulated docetaxel as a potential therapeutic strategy for the treatment of cholangiocarcinoma
BACKGROUND: Cholangiocarcinoma (CC) is one of the fatal malignant neoplasms with poor prognosis. The traditional chemotherapy has been resistant to CC and does not improve the quality of life. The aim of the present study is to investigate the potential of chondroitin sulphate (CS)-histamine (HS) bl...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350976/ https://www.ncbi.nlm.nih.gov/pubmed/25889600 http://dx.doi.org/10.1186/s12951-015-0066-8 |
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author | Du, Nan Song, Lin-Ping Li, Xiao-Song Wang, Lei Wan, Ling Ma, Hong-Ying Zhao, Hui |
author_facet | Du, Nan Song, Lin-Ping Li, Xiao-Song Wang, Lei Wan, Ling Ma, Hong-Ying Zhao, Hui |
author_sort | Du, Nan |
collection | PubMed |
description | BACKGROUND: Cholangiocarcinoma (CC) is one of the fatal malignant neoplasms with poor prognosis. The traditional chemotherapy has been resistant to CC and does not improve the quality of life. The aim of the present study is to investigate the potential of chondroitin sulphate (CS)-histamine (HS) block copolymer micelles to improve the chemotherapeutic efficacy of docetaxel (DTX). RESULTS: pH-responsive property of CS-HS micelles was utilized to achieve maximum therapeutic efficacy in CC. In the present study, docetaxel-loaded CS-HS micelles (CSH-DTX) controlled the release of drug in the basic pH while rapidly released its cargo in the tumor pH (pH 5 and 6.8) possibly due to the breakdown of polymeric micelles. A nanosize of <150 nm will allow its accumulation in the tumor interstitial spaces via EPR effect. CSH-DTX effectively killed the cancer kills in a time- and concentration-dependent manner and showed pronounced therapeutic action than that of free drug at all-time points. CSH-DTX resulted in higher apoptosis of cancer cells with ~30% and ~50 of cells in early apoptosis quadrant when treated with 100 and 1000 ng/ml of equivalent drug. The micellar formulations showed remarkable effect in controlling the tumor growth and reduced the overall tumor volume to 1/5(th) to that of control and half to that of free drug treated group with no sign of drug-related adverse effects. Immunohistochemical analysis of tumor sections showed that fewer number of Ki-67 cells were present in CSH-DTX treated group comparing to that of free DTX treated group. CONCLUSION: Our data suggests that nanoformulation of DTX could potentially improve the chemotherapy treatment in cholangiocarcinoma as well as in other malignancies. |
format | Online Article Text |
id | pubmed-4350976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-43509762015-03-06 Novel pH-sensitive nanoformulated docetaxel as a potential therapeutic strategy for the treatment of cholangiocarcinoma Du, Nan Song, Lin-Ping Li, Xiao-Song Wang, Lei Wan, Ling Ma, Hong-Ying Zhao, Hui J Nanobiotechnology Research BACKGROUND: Cholangiocarcinoma (CC) is one of the fatal malignant neoplasms with poor prognosis. The traditional chemotherapy has been resistant to CC and does not improve the quality of life. The aim of the present study is to investigate the potential of chondroitin sulphate (CS)-histamine (HS) block copolymer micelles to improve the chemotherapeutic efficacy of docetaxel (DTX). RESULTS: pH-responsive property of CS-HS micelles was utilized to achieve maximum therapeutic efficacy in CC. In the present study, docetaxel-loaded CS-HS micelles (CSH-DTX) controlled the release of drug in the basic pH while rapidly released its cargo in the tumor pH (pH 5 and 6.8) possibly due to the breakdown of polymeric micelles. A nanosize of <150 nm will allow its accumulation in the tumor interstitial spaces via EPR effect. CSH-DTX effectively killed the cancer kills in a time- and concentration-dependent manner and showed pronounced therapeutic action than that of free drug at all-time points. CSH-DTX resulted in higher apoptosis of cancer cells with ~30% and ~50 of cells in early apoptosis quadrant when treated with 100 and 1000 ng/ml of equivalent drug. The micellar formulations showed remarkable effect in controlling the tumor growth and reduced the overall tumor volume to 1/5(th) to that of control and half to that of free drug treated group with no sign of drug-related adverse effects. Immunohistochemical analysis of tumor sections showed that fewer number of Ki-67 cells were present in CSH-DTX treated group comparing to that of free DTX treated group. CONCLUSION: Our data suggests that nanoformulation of DTX could potentially improve the chemotherapy treatment in cholangiocarcinoma as well as in other malignancies. BioMed Central 2015-02-27 /pmc/articles/PMC4350976/ /pubmed/25889600 http://dx.doi.org/10.1186/s12951-015-0066-8 Text en © Du et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Du, Nan Song, Lin-Ping Li, Xiao-Song Wang, Lei Wan, Ling Ma, Hong-Ying Zhao, Hui Novel pH-sensitive nanoformulated docetaxel as a potential therapeutic strategy for the treatment of cholangiocarcinoma |
title | Novel pH-sensitive nanoformulated docetaxel as a potential therapeutic strategy for the treatment of cholangiocarcinoma |
title_full | Novel pH-sensitive nanoformulated docetaxel as a potential therapeutic strategy for the treatment of cholangiocarcinoma |
title_fullStr | Novel pH-sensitive nanoformulated docetaxel as a potential therapeutic strategy for the treatment of cholangiocarcinoma |
title_full_unstemmed | Novel pH-sensitive nanoformulated docetaxel as a potential therapeutic strategy for the treatment of cholangiocarcinoma |
title_short | Novel pH-sensitive nanoformulated docetaxel as a potential therapeutic strategy for the treatment of cholangiocarcinoma |
title_sort | novel ph-sensitive nanoformulated docetaxel as a potential therapeutic strategy for the treatment of cholangiocarcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350976/ https://www.ncbi.nlm.nih.gov/pubmed/25889600 http://dx.doi.org/10.1186/s12951-015-0066-8 |
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