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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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Intracellular doxorubicin in A549 cells.Notes: Doxorubicin uptake into A549 tumor cells after incubation with composite doxorubicin-loaded micelles or free doxorubicin for 4 hours, then compounds removed for one hour and 2.5 hours. Accumulation 4 hours: A549 cells incubated in composite doxorubicin-loaded micelles or free doxorubicin for 4 hours; release one hour. A549 cells incubated in composite doxorubicin-loaded micelles or free DOX for 4 hours, then compounds removed for one hour; release 2.5 hours, A549 cells incubated in composite doxorubicin-loaded micelles or free doxorubicin for 4 hours, then compounds removed for 2.5 hours.Abbreviations: DOX, free doxorubicin; MIX, composite doxorubicin-loaded micelles.
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f2-ijn-7-2661: Intracellular doxorubicin in A549 cells.Notes: Doxorubicin uptake into A549 tumor cells after incubation with composite doxorubicin-loaded micelles or free doxorubicin for 4 hours, then compounds removed for one hour and 2.5 hours. Accumulation 4 hours: A549 cells incubated in composite doxorubicin-loaded micelles or free doxorubicin for 4 hours; release one hour. A549 cells incubated in composite doxorubicin-loaded micelles or free DOX for 4 hours, then compounds removed for one hour; release 2.5 hours, A549 cells incubated in composite doxorubicin-loaded micelles or free doxorubicin for 4 hours, then compounds removed for 2.5 hours.Abbreviations: DOX, free doxorubicin; MIX, composite doxorubicin-loaded micelles.

Mentions: Internalization of composite doxorubicin-loaded micelles and free doxorubicin in the A549 tumor cells was examined by fluorescent high-pressure liquid chromatography. As shown in Figure 2, after 4 hours of incubation, envelopment of doxorubicin in the composite micelles significantly increased cellular accumulation of the drug. After treatment with composite doxorubicin-loaded micelles or free doxorubicin for 4 hours, followed by one-hour recovery and 2.5-hour recovery periods, envelopment of doxorubicin in the composite micelles produced significantly sustained cellular release of the drug.


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)

Intracellular doxorubicin in A549 cells.Notes: Doxorubicin uptake into A549 tumor cells after incubation with composite doxorubicin-loaded micelles or free doxorubicin for 4 hours, then compounds removed for one hour and 2.5 hours. Accumulation 4 hours: A549 cells incubated in composite doxorubicin-loaded micelles or free doxorubicin for 4 hours; release one hour. A549 cells incubated in composite doxorubicin-loaded micelles or free DOX for 4 hours, then compounds removed for one hour; release 2.5 hours, A549 cells incubated in composite doxorubicin-loaded micelles or free doxorubicin for 4 hours, then compounds removed for 2.5 hours.Abbreviations: DOX, free doxorubicin; MIX, composite doxorubicin-loaded micelles.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3368509&req=5

f2-ijn-7-2661: Intracellular doxorubicin in A549 cells.Notes: Doxorubicin uptake into A549 tumor cells after incubation with composite doxorubicin-loaded micelles or free doxorubicin for 4 hours, then compounds removed for one hour and 2.5 hours. Accumulation 4 hours: A549 cells incubated in composite doxorubicin-loaded micelles or free doxorubicin for 4 hours; release one hour. A549 cells incubated in composite doxorubicin-loaded micelles or free DOX for 4 hours, then compounds removed for one hour; release 2.5 hours, A549 cells incubated in composite doxorubicin-loaded micelles or free doxorubicin for 4 hours, then compounds removed for 2.5 hours.Abbreviations: DOX, free doxorubicin; MIX, composite doxorubicin-loaded micelles.
Mentions: Internalization of composite doxorubicin-loaded micelles and free doxorubicin in the A549 tumor cells was examined by fluorescent high-pressure liquid chromatography. As shown in Figure 2, after 4 hours of incubation, envelopment of doxorubicin in the composite micelles significantly increased cellular accumulation of the drug. After treatment with composite doxorubicin-loaded micelles or free doxorubicin for 4 hours, followed by one-hour recovery and 2.5-hour recovery periods, envelopment of doxorubicin in the composite micelles produced significantly sustained cellular release of the drug.

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