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

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.

Synthesis and Characterization of Folate-Targeted Dextran/Retinoic Acid Micelles for Doxorubicin Delivery in Acute Leukemia

“…DOX loading in the composite micelles significantly increased its cellular uptake, improved drug retention, and enhanced its antitumor effect relative to free DOX, thereby providing a novel approach for treatment of cancer [5]. …”

Therapeutic Apheresis, Circulating PLD, and Mucocutaneous Toxicity: Our Clinical Experience through Four Years

“…The combination of both treatments seems particularly advantageous against tumors sensitive to both radiotherapy and anthracyclines, such as breast carcinomas or sarcomas. In addition to radiotherapy, it may be possible to combine the therapeutic removal of excess circulating drugs with other modalities, such as hyperthermia [ 50 , 51 , 52 ], that can increase the effectiveness of chemotherapy through thermolabile liposomes, e.g., hyperthermia increases both PLD extravasation and doxorubicin release from liposomes in animal models [ 53 , 54 ]. While the advances made in clinical radiotherapy have driven many technological innovations, continuous improvement relies on the rational combination of different therapeutic strategies.…”

Octopod PtCu Nanoframe for Dual-Modal Imaging-Guided Synergistic Photothermal Radiotherapy

“…A colony formation assay of HepG2 cells irradiated by X-ray with different doses (0, 2, 4, 6, 8 and 10 Gy) was performed in presence or absence of OPCNs-PEG-FA. The results were fitted with a multitarget- single-hitting model using the following Equation 50 :…”