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Thermal modulation of intracellular drug distribution using thermoresponsive polymeric micelles
Intracellular distribution of free doxorubicin (DOX) or DOX-loaded in polymeric micelles with thermoresponsive outer shells of poly( N-isopropylacrylamide) or its copolymers in cultured human breast cancer cells (MCF-7) were investigated by fluorescence and confocal laser scanning microscopy. Free D...
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Published in: | Reactive & functional polymers 2007-11, Vol.67 (11), p.1398-1407 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Intracellular distribution of free doxorubicin (DOX) or DOX-loaded in polymeric micelles with thermoresponsive outer shells of poly(
N-isopropylacrylamide) or its copolymers in cultured human breast cancer cells (MCF-7) were investigated by fluorescence and confocal laser scanning microscopy. Free DOX accumulated rapidly and selectively in cell nuclei, independent of temperature changes. In contrast to free drugs, the intracellular distribution of DOX-loaded in the thermoresponsive polymeric micelles was significantly affected by temperature changes across lower critical solution temperature (LCST) of the micelles. Above the micelle LCST, DOX delivered by the micelles was localized uniformly inside of MCF-7 cells. By contrast, the amount of DOX delivered to MCF-7 cells drastically decreased below the micelle LCST due to minimal interaction of the micelles with cell membrane surfaces. These results clearly showed that the mechanism of the intracellular drug localization was different between free drugs and DOX-loaded in the micelles. The thermoresponsive micelles aggressively interacted with the cells and carried DOX into the cells
via triggered phase transition of the outer shells. In addition, much lower accumulation of free DOX was observed in the resistant cells compared to its parent sensitive MCF-7 due to the resistant mechanism. Of interest, DOX accumulation in the resistant cells was almost in the same level as with MCF-7 (sensitive) cells for the micelle system above the LCST. |
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ISSN: | 1381-5148 |
DOI: | 10.1016/j.reactfunctpolym.2007.07.056 |