Oxaliplatin-incorporated micelles eliminate both cancer stem-like and bulk cell populations in colorectal cancer

Ke Wang1,*, Lina Liu2,*, Tao Zhang1, Yong-liang Zhu3, Fuming Qiu4, Xian-guo Wu1, Xiao-lei Wang1, Fu-qiang Hu5, Jian Huang1,41Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education; Provincial Key Laboratory of Molecular Biology in Medical Sciences), Th...

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Autores principales:	Wang K, Liu L, Zhang T, Zhu YL, Qiu F, Wu XG, Wang XL, Hu FQ, Huang J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b7b956faa24e4532b23514fbfa5e1f48
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spelling	oai:doaj.org-article:b7b956faa24e4532b23514fbfa5e1f482021-12-02T02:46:49ZOxaliplatin-incorporated micelles eliminate both cancer stem-like and bulk cell populations in colorectal cancer1176-91141178-2013https://doaj.org/article/b7b956faa24e4532b23514fbfa5e1f482011-12-01T00:00:00Zhttp://www.dovepress.com/oxaliplatin-incorporated-micelles-eliminate-both-cancer-stem-like-and--a8800https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Ke Wang1,, Lina Liu2,, Tao Zhang1, Yong-liang Zhu3, Fuming Qiu4, Xian-guo Wu1, Xiao-lei Wang1, Fu-qiang Hu5, Jian Huang1,41Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education; Provincial Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine; 2Department of Pharmacy, Second Affiliated Hospital (Binjiang Branch), Zhejiang University School of Medicine; 3Department of Gastroenterology; 4Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine; 5College of Pharmaceutical Science, Zhejiang University, Hangzhou, China, , *These authors contributed equally to this workPurpose: The failure of cancer treatments is partly due to the enrichment of cancer stem-like cells (CSLCs) that are resistant to conventional chemotherapy. A novel micelle formulation of oxaliplatin (OXA) encapsulated in chitosan vesicle was developed. The authors postulate that micelle encapsulation of OXA would eliminate both CSLCs and bulk cancer cells in colorectal cancer (CRC).Experimental design: In this study, using stearic acid-g-chitosan oligosaccharide (CSO-SA) polymeric micelles as a drug-delivery system, OXA-loaded CSO-SA micelles (CSO-SA/OXA) were prepared. Intracellular uptake of CSO-SA/OXA micelles was assessed by confocal microscope. The effects of free OXA, the empty carrier, and CSO-SA/OXA micelles were tested using human CRC cell lines in vitro and in vivo.Results: The micelles showed excellent internalization ability that increased OXA accumulation both in CRC cells and tissues. Furthermore, CSO-SA/OXA micelles could either increase the cytotoxicity of OXA against the bulk cancer cells or reverse chemoresistance of CSLC subpopulations in vitro. Intravenous administration of CSO-SA/OXA micelles effectively suppressed the tumor growth and reduced CD133+/CD24+ cell (putative CRC CSLC markers) compared with free OXA treatment, which caused CSLC enrichment in xenograft tumors (P&nbsp;&lt; 0.05).Conclusion: The results of this study indicate that CSO-SA micelle as a drug-delivery carrier is effective for eradicating CSLCs and may act as a new option for CRC therapy.Keywords: polymeric micelle, chemotherapy resistance, tumorWang KLiu LZhang TZhu YLQiu FWu XGWang XLHu FQHuang JDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 3207-3218 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Wang K Liu L Zhang T Zhu YL Qiu F Wu XG Wang XL Hu FQ Huang J Oxaliplatin-incorporated micelles eliminate both cancer stem-like and bulk cell populations in colorectal cancer
description	Ke Wang1,, Lina Liu2,, Tao Zhang1, Yong-liang Zhu3, Fuming Qiu4, Xian-guo Wu1, Xiao-lei Wang1, Fu-qiang Hu5, Jian Huang1,41Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education; Provincial Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine; 2Department of Pharmacy, Second Affiliated Hospital (Binjiang Branch), Zhejiang University School of Medicine; 3Department of Gastroenterology; 4Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine; 5College of Pharmaceutical Science, Zhejiang University, Hangzhou, China, , *These authors contributed equally to this workPurpose: The failure of cancer treatments is partly due to the enrichment of cancer stem-like cells (CSLCs) that are resistant to conventional chemotherapy. A novel micelle formulation of oxaliplatin (OXA) encapsulated in chitosan vesicle was developed. The authors postulate that micelle encapsulation of OXA would eliminate both CSLCs and bulk cancer cells in colorectal cancer (CRC).Experimental design: In this study, using stearic acid-g-chitosan oligosaccharide (CSO-SA) polymeric micelles as a drug-delivery system, OXA-loaded CSO-SA micelles (CSO-SA/OXA) were prepared. Intracellular uptake of CSO-SA/OXA micelles was assessed by confocal microscope. The effects of free OXA, the empty carrier, and CSO-SA/OXA micelles were tested using human CRC cell lines in vitro and in vivo.Results: The micelles showed excellent internalization ability that increased OXA accumulation both in CRC cells and tissues. Furthermore, CSO-SA/OXA micelles could either increase the cytotoxicity of OXA against the bulk cancer cells or reverse chemoresistance of CSLC subpopulations in vitro. Intravenous administration of CSO-SA/OXA micelles effectively suppressed the tumor growth and reduced CD133+/CD24+ cell (putative CRC CSLC markers) compared with free OXA treatment, which caused CSLC enrichment in xenograft tumors (P&nbsp;&lt; 0.05).Conclusion: The results of this study indicate that CSO-SA micelle as a drug-delivery carrier is effective for eradicating CSLCs and may act as a new option for CRC therapy.Keywords: polymeric micelle, chemotherapy resistance, tumor
format	article
author	Wang K Liu L Zhang T Zhu YL Qiu F Wu XG Wang XL Hu FQ Huang J
author_facet	Wang K Liu L Zhang T Zhu YL Qiu F Wu XG Wang XL Hu FQ Huang J
author_sort	Wang K
title	Oxaliplatin-incorporated micelles eliminate both cancer stem-like and bulk cell populations in colorectal cancer
title_short	Oxaliplatin-incorporated micelles eliminate both cancer stem-like and bulk cell populations in colorectal cancer
title_full	Oxaliplatin-incorporated micelles eliminate both cancer stem-like and bulk cell populations in colorectal cancer
title_fullStr	Oxaliplatin-incorporated micelles eliminate both cancer stem-like and bulk cell populations in colorectal cancer
title_full_unstemmed	Oxaliplatin-incorporated micelles eliminate both cancer stem-like and bulk cell populations in colorectal cancer
title_sort	oxaliplatin-incorporated micelles eliminate both cancer stem-like and bulk cell populations in colorectal cancer
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/b7b956faa24e4532b23514fbfa5e1f48
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Oxaliplatin-incorporated micelles eliminate both cancer stem-like and bulk cell populations in colorectal cancer

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