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

Xu WH, Han M, Dong Q, Fu ZX, Diao YY, Liu H, Xu J, Jiang HL, Zhang SZ, Zheng S, Gao JQ, Wei QC - Int J Nanomedicine (2012)

Bottom Line: Doxorubicin radiosensitization and the combined effects of irradiation and doxorubicin on cell migration and proliferation were compared for the different doxorubicin delivery systems.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

ABSTRACT

Background: The purpose of this study is to evaluate the efficacy of composite doxorubicinloaded 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 glycolpolycaprolactone/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.

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Tumor cell migration from spheroids following irradiation and combination treatment (radiation alone + blank composite micelles, radiation alone + doxorubicin, radiation alone + MIX). Mean area of tumor cell migration (mm2).Notes: Each treatment group (sham, irradiation alone, blank composite micelle + irradiation, free doxorubicin + irradiation, composite doxorubicin-loaded micelle + irradiation) consists of 30 A549 spheroids in five independent experiments. Changes at day 4 were significant (P < 0.05).Abbreviations: DOX, free doxorubicin; MIX, composite doxorubicin-loaded micelles; RT, radiation alone.
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f7-ijn-7-2661: Tumor cell migration from spheroids following irradiation and combination treatment (radiation alone + blank composite micelles, radiation alone + doxorubicin, radiation alone + MIX). Mean area of tumor cell migration (mm2).Notes: Each treatment group (sham, irradiation alone, blank composite micelle + irradiation, free doxorubicin + irradiation, composite doxorubicin-loaded micelle + irradiation) consists of 30 A549 spheroids in five independent experiments. Changes at day 4 were significant (P < 0.05).Abbreviations: DOX, free doxorubicin; MIX, composite doxorubicin-loaded micelles; RT, radiation alone.

Mentions: Cell migration was determined for both treated and untreated spheroids. A significant growth reduction of 30% and 28%, respectively, was seen in the irradiation only group and the blank composite micelles + irradiation group after 4 days. There was no statistically significant difference between the irradiation only group and the blank composite micelles + irradiation group. However, combined treatment with equivalent concentrations of free doxorubicin or composite doxorubicin-loaded micelles had a significant additive effect on growth reduction of 46% and 61%, respectively (Figure 7).


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

Xu WH, Han M, Dong Q, Fu ZX, Diao YY, Liu H, Xu J, Jiang HL, Zhang SZ, Zheng S, Gao JQ, Wei QC - Int J Nanomedicine (2012)

Tumor cell migration from spheroids following irradiation and combination treatment (radiation alone + blank composite micelles, radiation alone + doxorubicin, radiation alone + MIX). Mean area of tumor cell migration (mm2).Notes: Each treatment group (sham, irradiation alone, blank composite micelle + irradiation, free doxorubicin + irradiation, composite doxorubicin-loaded micelle + irradiation) consists of 30 A549 spheroids in five independent experiments. Changes at day 4 were significant (P < 0.05).Abbreviations: DOX, free doxorubicin; MIX, composite doxorubicin-loaded micelles; RT, radiation alone.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3368509&req=5

f7-ijn-7-2661: Tumor cell migration from spheroids following irradiation and combination treatment (radiation alone + blank composite micelles, radiation alone + doxorubicin, radiation alone + MIX). Mean area of tumor cell migration (mm2).Notes: Each treatment group (sham, irradiation alone, blank composite micelle + irradiation, free doxorubicin + irradiation, composite doxorubicin-loaded micelle + irradiation) consists of 30 A549 spheroids in five independent experiments. Changes at day 4 were significant (P < 0.05).Abbreviations: DOX, free doxorubicin; MIX, composite doxorubicin-loaded micelles; RT, radiation alone.
Mentions: Cell migration was determined for both treated and untreated spheroids. A significant growth reduction of 30% and 28%, respectively, was seen in the irradiation only group and the blank composite micelles + irradiation group after 4 days. There was no statistically significant difference between the irradiation only group and the blank composite micelles + irradiation group. However, combined treatment with equivalent concentrations of free doxorubicin or composite doxorubicin-loaded micelles had a significant additive effect on growth reduction of 46% and 61%, respectively (Figure 7).

Bottom Line: Doxorubicin radiosensitization and the combined effects of irradiation and doxorubicin on cell migration and proliferation were compared for the different doxorubicin delivery systems.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

ABSTRACT

Background: The purpose of this study is to evaluate the efficacy of composite doxorubicinloaded 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 glycolpolycaprolactone/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.

Show MeSH
Related in: MedlinePlus