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Polymers 2014, 6(3), 634-650; doi:10.3390/polym6030634

Endocytosis Pathways of the Folate Tethered Star-Shaped PEG-PCL Micelles in Cancer Cell Lines

1
Department of Biomedical Engineering, Chung Yuan Christian University, No. 200, Chung-Pei Rd., Chung Li 32023, Taiwan
2
Center for Nanotechnology, Chung Yuan Christian University, 200, Chung-Pei Rd., Chung Li 32023, Taiwan
3
Center of Biomedical Technology, Chung Yuan Christian University, 200, Chung-Pei Rd., Chung Li 32023, Taiwan
4
Department of Chemical Engineering, Industrial University of Ho Chi Minh City, 12 Nguyen Van Bao Road, GoVap Dist., Ho Cho Minh City 7000, Vietnam
*
Author to whom correspondence should be addressed.
Received: 17 December 2013 / Revised: 20 February 2014 / Accepted: 24 February 2014 / Published: 6 March 2014
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Abstract

This study reports on the cellular uptake of folate tethered micelles using a branched skeleton of poly(ethylene glycol) and poly(ε-caprolactone). The chemical structures of the copolymers were characterized by proton nuclear magnetic resonance spectroscopy, and Fourier transform infrared spectroscopy. Doxorubicin (DOX) was utilized as an anticancer drug. The highest drug loading efficiencies of DOX in the folate decorated micelle (DMCF) and folate-free micelle (DMC) were found to be 88.5% and 88.2%, respectively, depending on the segment length of the poly(ε-caprolactone) in the copolymers. A comparison of fluorescent microscopic images of the endocytosis pathway in two cell lines, human breast cancer cells (MCF-7) and human oral cavity carcinoma cells (KB), revealed that the micelles were engulfed by KB and MCF-7 cells following in vitro incubation for one hour. Flow cytometric analysis revealed that free folic acid can inhibit the uptake of DOX by 48%–57% and 26%–39% in KB cells and MCF-7 cells, respectively. These results prove that KB cells are relatively sensitive to folate-tethered micelles. Upon administering methyl-β-cyclodextrin, an inhibitor of the caveolae-mediated endocytosis pathway, the uptake of DOX by KB cells was reduced by 69% and that by MCF-7 cells was reduced by 56%. This finding suggests that DMCF enters cells via multiple pathways, thus implying that the folate receptor is not the only target of tumor therapeutics.
Keywords: copolymer; drug delivery targeting; endocytosis pathway; folate receptor copolymer; drug delivery targeting; endocytosis pathway; folate receptor
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Li, Y.-L.; Van Cuong, N.; Hsieh, M.-F. Endocytosis Pathways of the Folate Tethered Star-Shaped PEG-PCL Micelles in Cancer Cell Lines. Polymers 2014, 6, 634-650.

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