Back to Journals » International Journal of Nanomedicine » Volume 7

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

Authors Xu W, Han M, Dong Q, Fu Z, Diao, Liu H, Xu J, Jiang H, Zhang S, Zheng S, Gao J, Wei Q

Received 1 February 2012

Accepted for publication 17 April 2012

Published 29 May 2012 Volume 2012:7 Pages 2661—2671


Review by Single-blind

Peer reviewer comments 3

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 Wei1
1Department 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, China

Background: 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

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]


Readers of this article also read:

Comparison of the clinical features and outcomes in two age-groups of elderly patients with atrial fibrillation

Shao XH, Yang YM, Zhu J, Zhang H, Liu Y, Gao X, Yu LT, Liu LS, Zhao L, Yu PF, Zhang H, He Q, Gu XD

Clinical Interventions in Aging 2014, 9:1335-1342

Published Date: 12 August 2014

Chemotherapeutic potential of curcumin-bearing microcells against hepatocellular carcinoma in model animals

Farazuddin M, Dua B, Zia Q, Khan AA, Joshi B, Owais M

International Journal of Nanomedicine 2014, 9:1139-1152

Published Date: 3 March 2014

Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4

Shiozaki Y, Kitajima T, Mazaki T, Yoshida A, Tanaka M, Umezawa A, Nakamura M, Yoshida Y, Ito Y, Ozaki T, Matsukawa A

International Journal of Nanomedicine 2013, 8:1349-1360

Published Date: 9 April 2013


Cárdenas WH, Mamani JB, Sibov TT, Caous CA, Amaro E Jr, Gamarra LF

International Journal of Nanomedicine 2012, 7:5107-5108

Published Date: 21 September 2012

Gene-carried hepatoma targeting complex induced high gene transfection efficiency with low toxicity and significant antitumor activity

Zhao QQ, Hu YL, Zhou Y, Li N, Han M, Tang GP, Qiu F, Tabata Y, Gao JQ

International Journal of Nanomedicine 2012, 7:3191-3202

Published Date: 27 June 2012

Cell type-dependent uptake, localization, and cytotoxicity of 1.9 nm gold nanoparticles

Coulter JA, Jain S, Butterworth KT, Taggart LE, Dickson GR, McMahon SJ, Hyland WB, Muir MF, Trainor C, Hounsell AR, O'Sullivan JM, Schettino G, Currell FJ, Hirst DG, Prise KM

International Journal of Nanomedicine 2012, 7:2673-2685

Published Date: 1 June 2012

Erratum - Intracellular heavy metal nanoparticle storage

Iannitti T, Capone S, Gatti A, et al

International Journal of Nanomedicine 2011, 6:239-240

Published Date: 26 January 2011

In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection

Torben Gjetting, Nicolai Skovbjerg Arildsen, Camilla Laulund, et al

International Journal of Nanomedicine 2010, 5:371-383

Published Date: 25 May 2010