Doxorubicin-mediated radiosensitivity in multicellular spheroids from a lung cancer cell line is enhanced by composite micelle encapsulation

Wen-Hong Xu,1 Min Han,2 Qi Dong,3 Zhi-Xuan Fu,3 Yuan-Yuan Diao,2 Hai Liu,3 Jing Xu,3 Hong-Liang Jiang,4 Su-Zhan Zhang,3 Shu Zheng,3 Jian-Qing Gao,2 Qi-Chun Wei11Department of Radiation Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, 2Institute of Pharmaceutics, Col...

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Autores principales:	Xu WH, Han M, Dong Q, Fu ZX, Diao YY, Liu H, Xu J, Jiang HL, Zhang SZ, Zheng S, Gao JQ, Wei QC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/68b55e5183df4bc097b1eb2a3cb82052
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spelling	oai:doaj.org-article:68b55e5183df4bc097b1eb2a3cb820522021-12-02T02:39:46ZDoxorubicin-mediated radiosensitivity in multicellular spheroids from a lung cancer cell line is enhanced by composite micelle encapsulation1176-91141178-2013https://doaj.org/article/68b55e5183df4bc097b1eb2a3cb820522012-05-01T00:00:00Zhttp://www.dovepress.com/doxorubicin-mediated-radiosensitivity-in-multicellular-spheroids-from--a9996https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Wen-Hong Xu,1 Min Han,2 Qi Dong,3 Zhi-Xuan Fu,3 Yuan-Yuan Diao,2 Hai Liu,3 Jing Xu,3 Hong-Liang Jiang,4 Su-Zhan Zhang,3 Shu Zheng,3 Jian-Qing Gao,2 Qi-Chun Wei11Department of Radiation Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, 2Institute of Pharmaceutics, College of Pharmaceutical Sciences, 3Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, 4Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, ChinaBackground: The purpose of this study is to evaluate the efficacy of composite doxorubicin-loaded micelles for enhancing doxorubicin radiosensitivity in multicellular spheroids from a non-small cell lung cancer cell line.Methods: A novel composite doxorubicin-loaded micelle consisting of polyethylene glycol-polycaprolactone/Pluronic P105 was developed, and carrier-mediated doxorubicin accumulation and release from multicellular spheroids was evaluated. We used confocal laser scanning microscopy and flow cytometry to study the accumulation and efflux of doxorubicin from A549 multicellular spheroids. Doxorubicin radiosensitization and the combined effects of irradiation and doxorubicin on cell migration and proliferation were compared for the different doxorubicin delivery systems.Results: Confocal laser scanning microscopy and quantitative flow cytometry studies both verified that, for equivalent doxorubicin concentrations, composite doxorubicin-loaded micelles significantly enhanced cellular doxorubicin accumulation and inhibited doxorubicin release. Colony-forming assays demonstrated that composite doxorubicin-loaded micelles are radiosensitive, as shown by significantly reduced survival of cells treated by radiation + composite micelles compared with those treated with radiation + free doxorubicin or radiation alone. The multicellular spheroid migration area and growth ability verified higher radiosensitivity for the composite micelles loaded with doxorubicin than for free doxorubicin.Conclusion: Our composite doxorubicin-loaded micelle was demonstrated to have radiosensitization. Doxorubicin loading in the composite micelles significantly increased its cellular uptake, improved drug retention, and enhanced its antitumor effect relative to free doxorubicin, thereby providing a novel approach for treatment of cancer.Keywords: doxorubicin, lung cancer, micelles, radiosensitivity, spheroidsXu WHHan MDong QFu ZXDiao YYLiu HXu JJiang HLZhang SZZheng SGao JQWei QCDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 2661-2671 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Xu WH Han M Dong Q Fu ZX Diao YY Liu H Xu J Jiang HL Zhang SZ Zheng S Gao JQ Wei QC Doxorubicin-mediated radiosensitivity in multicellular spheroids from a lung cancer cell line is enhanced by composite micelle encapsulation
description	Wen-Hong Xu,1 Min Han,2 Qi Dong,3 Zhi-Xuan Fu,3 Yuan-Yuan Diao,2 Hai Liu,3 Jing Xu,3 Hong-Liang Jiang,4 Su-Zhan Zhang,3 Shu Zheng,3 Jian-Qing Gao,2 Qi-Chun Wei11Department of Radiation Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, 2Institute of Pharmaceutics, College of Pharmaceutical Sciences, 3Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, 4Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, ChinaBackground: The purpose of this study is to evaluate the efficacy of composite doxorubicin-loaded micelles for enhancing doxorubicin radiosensitivity in multicellular spheroids from a non-small cell lung cancer cell line.Methods: A novel composite doxorubicin-loaded micelle consisting of polyethylene glycol-polycaprolactone/Pluronic P105 was developed, and carrier-mediated doxorubicin accumulation and release from multicellular spheroids was evaluated. We used confocal laser scanning microscopy and flow cytometry to study the accumulation and efflux of doxorubicin from A549 multicellular spheroids. Doxorubicin radiosensitization and the combined effects of irradiation and doxorubicin on cell migration and proliferation were compared for the different doxorubicin delivery systems.Results: Confocal laser scanning microscopy and quantitative flow cytometry studies both verified that, for equivalent doxorubicin concentrations, composite doxorubicin-loaded micelles significantly enhanced cellular doxorubicin accumulation and inhibited doxorubicin release. Colony-forming assays demonstrated that composite doxorubicin-loaded micelles are radiosensitive, as shown by significantly reduced survival of cells treated by radiation + composite micelles compared with those treated with radiation + free doxorubicin or radiation alone. The multicellular spheroid migration area and growth ability verified higher radiosensitivity for the composite micelles loaded with doxorubicin than for free doxorubicin.Conclusion: Our composite doxorubicin-loaded micelle was demonstrated to have radiosensitization. Doxorubicin loading in the composite micelles significantly increased its cellular uptake, improved drug retention, and enhanced its antitumor effect relative to free doxorubicin, thereby providing a novel approach for treatment of cancer.Keywords: doxorubicin, lung cancer, micelles, radiosensitivity, spheroids
format	article
author	Xu WH Han M Dong Q Fu ZX Diao YY Liu H Xu J Jiang HL Zhang SZ Zheng S Gao JQ Wei QC
author_facet	Xu WH Han M Dong Q Fu ZX Diao YY Liu H Xu J Jiang HL Zhang SZ Zheng S Gao JQ Wei QC
author_sort	Xu WH
title	Doxorubicin-mediated radiosensitivity in multicellular spheroids from a lung cancer cell line is enhanced by composite micelle encapsulation
title_short	Doxorubicin-mediated radiosensitivity in multicellular spheroids from a lung cancer cell line is enhanced by composite micelle encapsulation
title_full	Doxorubicin-mediated radiosensitivity in multicellular spheroids from a lung cancer cell line is enhanced by composite micelle encapsulation
title_fullStr	Doxorubicin-mediated radiosensitivity in multicellular spheroids from a lung cancer cell line is enhanced by composite micelle encapsulation
title_full_unstemmed	Doxorubicin-mediated radiosensitivity in multicellular spheroids from a lung cancer cell line is enhanced by composite micelle encapsulation
title_sort	doxorubicin-mediated radiosensitivity in multicellular spheroids from a lung cancer cell line is enhanced by composite micelle encapsulation
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/68b55e5183df4bc097b1eb2a3cb82052
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Doxorubicin-mediated radiosensitivity in multicellular spheroids from a lung cancer cell line is enhanced by composite micelle encapsulation

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