Endocytosis Pathways of the Folate Tethered Star-Shaped PEG-PCL Micelles in Cancer Cell Lines
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 spectrosco...
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| Format: | Article |
| Language: | English |
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MDPI AG
2014-03-01
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| Series: | Polymers |
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| Online Access: | http://www.mdpi.com/2073-4360/6/3/634 |
| _version_ | 1811230425696174080 |
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| author | Yu-Lun Li Nguyen Van Cuong Ming-Fa Hsieh |
| author_facet | Yu-Lun Li Nguyen Van Cuong Ming-Fa Hsieh |
| author_sort | Yu-Lun Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T10:29:06Z |
| format | Article |
| id | doaj.art-380f70cd8b7341ecace57dbb06c9a58f |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-04-12T10:29:06Z |
| publishDate | 2014-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Polymers |
| spelling | doaj.art-380f70cd8b7341ecace57dbb06c9a58f2022-12-22T03:36:54ZengMDPI AGPolymers2073-43602014-03-016363465010.3390/polym6030634polym6030634Endocytosis Pathways of the Folate Tethered Star-Shaped PEG-PCL Micelles in Cancer Cell LinesYu-Lun Li0Nguyen Van Cuong1Ming-Fa Hsieh2Department of Biomedical Engineering, Chung Yuan Christian University, No. 200, Chung-Pei Rd., Chung Li 32023, TaiwanDepartment of Biomedical Engineering, Chung Yuan Christian University, No. 200, Chung-Pei Rd., Chung Li 32023, TaiwanDepartment of Biomedical Engineering, Chung Yuan Christian University, No. 200, Chung-Pei Rd., Chung Li 32023, TaiwanThis 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.http://www.mdpi.com/2073-4360/6/3/634copolymerdrug delivery targetingendocytosis pathwayfolate receptor |
| spellingShingle | Yu-Lun Li Nguyen Van Cuong Ming-Fa Hsieh Endocytosis Pathways of the Folate Tethered Star-Shaped PEG-PCL Micelles in Cancer Cell Lines Polymers copolymer drug delivery targeting endocytosis pathway folate receptor |
| title | Endocytosis Pathways of the Folate Tethered Star-Shaped PEG-PCL Micelles in Cancer Cell Lines |
| title_full | Endocytosis Pathways of the Folate Tethered Star-Shaped PEG-PCL Micelles in Cancer Cell Lines |
| title_fullStr | Endocytosis Pathways of the Folate Tethered Star-Shaped PEG-PCL Micelles in Cancer Cell Lines |
| title_full_unstemmed | Endocytosis Pathways of the Folate Tethered Star-Shaped PEG-PCL Micelles in Cancer Cell Lines |
| title_short | Endocytosis Pathways of the Folate Tethered Star-Shaped PEG-PCL Micelles in Cancer Cell Lines |
| title_sort | endocytosis pathways of the folate tethered star shaped peg pcl micelles in cancer cell lines |
| topic | copolymer drug delivery targeting endocytosis pathway folate receptor |
| url | http://www.mdpi.com/2073-4360/6/3/634 |
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