Hyaluronan-conjugated liposomes encapsulating gemcitabine for breast cancer stem cells

Na-Kyung Han,1,* Dae Hwan Shin,1,* Jung Seok Kim,1 Kwon Yeon Weon,2 Chang-Young Jang,1 Jin-Seok Kim1 1Research Center for Cell Fate Control (RCCFC) and College of Pharmacy, Sookmyung Women’s University, Seoul, 2College of Pharmacy, Catholic University of Daegu, Gyeongbuk, Korea *These au...

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Autores principales:	Han NK, Shin DH, Kim JS, Weon KY, Jang CY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	gemcitabine liposome breast cancer stem cells hyaluronan targeting Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6e6218a78ad041b3b1be2f7de486a75a
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spelling	oai:doaj.org-article:6e6218a78ad041b3b1be2f7de486a75a2021-12-02T03:58:39ZHyaluronan-conjugated liposomes encapsulating gemcitabine for breast cancer stem cells1178-2013https://doaj.org/article/6e6218a78ad041b3b1be2f7de486a75a2016-04-01T00:00:00Zhttps://www.dovepress.com/hyaluronan-conjugated-liposomes-encapsulating-gemcitabine-for-breast-c-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Na-Kyung Han,1,* Dae Hwan Shin,1,* Jung Seok Kim,1 Kwon Yeon Weon,2 Chang-Young Jang,1 Jin-Seok Kim1 1Research Center for Cell Fate Control (RCCFC) and College of Pharmacy, Sookmyung Women’s University, Seoul, 2College of Pharmacy, Catholic University of Daegu, Gyeongbuk, Korea *These authors contributed equally to this work Abstract: Investigation of potential therapeutics for targeting breast cancer stem cells (BCSCs) is important because these cells are regarded as culprit of breast cancer relapse. Accomplishing this kind of strategy requires a specific drug-delivery system using the distinct features of liposomes. Studies on targeted liposomal delivery systems have indicated the conjugation of hyaluronan (HA), a primary ligand for CD44 surface markers, as an appropriate method for targeting BCSCs. For this study, enriched BCSCs were obtained by culturing MCF-7 breast cancer cells in nonadherent conditions. The enriched BCSCs were challenged with HA-conjugated liposomes encapsulating gemcitabine (2, 2-difluoro-2-deoxycytidine, GEM). In vitro study showed that the HA-conjugated liposomes significantly enhanced the cytotoxicity, anti-migration, and anti-colony formation abilities of GEM through targeting of CD44 expressed on BCSCs. In pharmacokinetic study, area under the drug concentration vs time curve (AUC) of the immunoliposomal GEM was 3.5 times higher than that of free GEM, indicating that the HA-conjugated liposomes enhanced the stability of GEM in the bloodstream and therefore prolonged its half-life time. The antitumor effect of the immunoliposomal GEM was 3.3 times higher than that of free GEM in a xenograft mouse model, probably reflecting the unique targeting of the CD44 receptor by HA and the increased cytotoxicity and stability through the liposomal formulation. Furthermore, marginal change in body weight demonstrated that the use of liposomes considerably reduced the systemic toxicity of GEM on normal healthy cells. Taken together, this study demonstrates that HA-conjugated liposomes encapsulating GEM show promise for the therapy of breast cancer in vitro and in a xenograft model by targeting the BCSCs. Keywords: breast cancer stem cells, targeting, CD44 surface marker, EPR effect, drug delivery systemHan NKShin DHKim JSWeon KYJang CYKim JSDove Medical Pressarticlegemcitabineliposomebreast cancer stem cellshyaluronantargetingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 1413-1425 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	gemcitabine liposome breast cancer stem cells hyaluronan targeting Medicine (General) R5-920
spellingShingle	gemcitabine liposome breast cancer stem cells hyaluronan targeting Medicine (General) R5-920 Han NK Shin DH Kim JS Weon KY Jang CY Kim JS Hyaluronan-conjugated liposomes encapsulating gemcitabine for breast cancer stem cells
description	Na-Kyung Han,1,* Dae Hwan Shin,1,* Jung Seok Kim,1 Kwon Yeon Weon,2 Chang-Young Jang,1 Jin-Seok Kim1 1Research Center for Cell Fate Control (RCCFC) and College of Pharmacy, Sookmyung Women’s University, Seoul, 2College of Pharmacy, Catholic University of Daegu, Gyeongbuk, Korea *These authors contributed equally to this work Abstract: Investigation of potential therapeutics for targeting breast cancer stem cells (BCSCs) is important because these cells are regarded as culprit of breast cancer relapse. Accomplishing this kind of strategy requires a specific drug-delivery system using the distinct features of liposomes. Studies on targeted liposomal delivery systems have indicated the conjugation of hyaluronan (HA), a primary ligand for CD44 surface markers, as an appropriate method for targeting BCSCs. For this study, enriched BCSCs were obtained by culturing MCF-7 breast cancer cells in nonadherent conditions. The enriched BCSCs were challenged with HA-conjugated liposomes encapsulating gemcitabine (2, 2-difluoro-2-deoxycytidine, GEM). In vitro study showed that the HA-conjugated liposomes significantly enhanced the cytotoxicity, anti-migration, and anti-colony formation abilities of GEM through targeting of CD44 expressed on BCSCs. In pharmacokinetic study, area under the drug concentration vs time curve (AUC) of the immunoliposomal GEM was 3.5 times higher than that of free GEM, indicating that the HA-conjugated liposomes enhanced the stability of GEM in the bloodstream and therefore prolonged its half-life time. The antitumor effect of the immunoliposomal GEM was 3.3 times higher than that of free GEM in a xenograft mouse model, probably reflecting the unique targeting of the CD44 receptor by HA and the increased cytotoxicity and stability through the liposomal formulation. Furthermore, marginal change in body weight demonstrated that the use of liposomes considerably reduced the systemic toxicity of GEM on normal healthy cells. Taken together, this study demonstrates that HA-conjugated liposomes encapsulating GEM show promise for the therapy of breast cancer in vitro and in a xenograft model by targeting the BCSCs. Keywords: breast cancer stem cells, targeting, CD44 surface marker, EPR effect, drug delivery system
format	article
author	Han NK Shin DH Kim JS Weon KY Jang CY Kim JS
author_facet	Han NK Shin DH Kim JS Weon KY Jang CY Kim JS
author_sort	Han NK
title	Hyaluronan-conjugated liposomes encapsulating gemcitabine for breast cancer stem cells
title_short	Hyaluronan-conjugated liposomes encapsulating gemcitabine for breast cancer stem cells
title_full	Hyaluronan-conjugated liposomes encapsulating gemcitabine for breast cancer stem cells
title_fullStr	Hyaluronan-conjugated liposomes encapsulating gemcitabine for breast cancer stem cells
title_full_unstemmed	Hyaluronan-conjugated liposomes encapsulating gemcitabine for breast cancer stem cells
title_sort	hyaluronan-conjugated liposomes encapsulating gemcitabine for breast cancer stem cells
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/6e6218a78ad041b3b1be2f7de486a75a
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Hyaluronan-conjugated liposomes encapsulating gemcitabine for breast cancer stem cells

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