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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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Related in: MedlinePlus

Spheroid proliferation following single mode and combinational treatment.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. Illustration of mean volume growth of spheroids following irradiation and irradiation alone + blank composite micelles, irradiation alone + doxorubicin, irradiation alone + MIX (composite doxorubicin-loaded micelles). A significant reduction in spheroid volume was observed following irradiation alone + MIX on day 9 (P < 0.05).Abbreviations: DOX, free doxorubicin; MIX, composite doxorubicin-loaded micelles; RT, radiation alone.
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f8-ijn-7-2661: Spheroid proliferation following single mode and combinational treatment.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. Illustration of mean volume growth of spheroids following irradiation and irradiation alone + blank composite micelles, irradiation alone + doxorubicin, irradiation alone + MIX (composite doxorubicin-loaded micelles). A significant reduction in spheroid volume was observed following irradiation alone + MIX on day 9 (P < 0.05).Abbreviations: DOX, free doxorubicin; MIX, composite doxorubicin-loaded micelles; RT, radiation alone.

Mentions: The proliferation capacity of spheroids treated with equivalent concentrations of doxorubicin or MIX was determined. Following irradiation alone and blank composite micelles + irradiation, the spheroids showed significant growth reduction of 44% and 47%, respectively, after 9 days. There was no difference between the irradiation only group and the blank composite micelles + irradiation group. However, following combined treatment, the spheroids showed significantly increased growth reduction of 58% (for radiation + free doxorubicin) and 77% (for radiation + MIX) after nine days (Figure 8).


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)

Spheroid proliferation following single mode and combinational treatment.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. Illustration of mean volume growth of spheroids following irradiation and irradiation alone + blank composite micelles, irradiation alone + doxorubicin, irradiation alone + MIX (composite doxorubicin-loaded micelles). A significant reduction in spheroid volume was observed following irradiation alone + MIX on day 9 (P < 0.05).Abbreviations: DOX, free doxorubicin; MIX, composite doxorubicin-loaded micelles; RT, radiation alone.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368509&req=5

f8-ijn-7-2661: Spheroid proliferation following single mode and combinational treatment.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. Illustration of mean volume growth of spheroids following irradiation and irradiation alone + blank composite micelles, irradiation alone + doxorubicin, irradiation alone + MIX (composite doxorubicin-loaded micelles). A significant reduction in spheroid volume was observed following irradiation alone + MIX on day 9 (P < 0.05).Abbreviations: DOX, free doxorubicin; MIX, composite doxorubicin-loaded micelles; RT, radiation alone.
Mentions: The proliferation capacity of spheroids treated with equivalent concentrations of doxorubicin or MIX was determined. Following irradiation alone and blank composite micelles + irradiation, the spheroids showed significant growth reduction of 44% and 47%, respectively, after 9 days. There was no difference between the irradiation only group and the blank composite micelles + irradiation group. However, following combined treatment, the spheroids showed significantly increased growth reduction of 58% (for radiation + free doxorubicin) and 77% (for radiation + MIX) after nine days (Figure 8).

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