Tumor Cell Targeting and Endocytosis Pathways of Doxorubicin Loaded Folate-Conjugated Polymeric Micelles
碩士 === 中原大學 === 生物醫學工程研究所 === 100 === The specificity between normal cells and cancer cells in conventional chemotherapy is in-sufficient. The plasma surface of cancer cells is expressed various receptors depending on the physiological functions of the cells. Folate receptor (FR) is overexpressed in...
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ndltd-TW-100CYCU51140072015-10-13T21:32:34Z http://ndltd.ncl.edu.tw/handle/49896646013671045460 Tumor Cell Targeting and Endocytosis Pathways of Doxorubicin Loaded Folate-Conjugated Polymeric Micelles 搭載艾黴素之葉酸接枝高分子微胞對腫瘤細胞的標靶性及細胞吞噬路徑探討 Yu-Lun Li 李毓倫 碩士 中原大學 生物醫學工程研究所 100 The specificity between normal cells and cancer cells in conventional chemotherapy is in-sufficient. The plasma surface of cancer cells is expressed various receptors depending on the physiological functions of the cells. Folate receptor (FR) is overexpressed in the apical membrane surface of certain cancer cells making a potential target of tumor therapeutics. Hence, in this study, folate-decorated micelles based on the star-shaped PCL-PEG copolymer were prepared for targeting to the folate receptor overexpressing in human oral cavity carcinoma cells (KB) and human breast cancer cells (MCF-7). The structure and molecular weight of micelle materials was characterized by FT-IR and 1H NMR. The of 4SPCL50-PEG-Folate、4SPCL100-PEG-Folate and 4SPCL150-PEG-Folate are 17168、23361 and 28680 g/mol, respectively. The doxorubicin-loaded micelles were prepared using dialysis method (DMC50F、DMC100F、DMC150F). The particle size of the DOX-loaded micelle was 126.2、128.7 and 123.1 nm, respectively. The drug loading efficiency were 76、88.5 and 33.5 %, respectively. The total release of DOX in a period of 60 h at pH 7.4 and 5.4 account for 29 % and 84 % of total DOX concentration loaded; respectively. The IC50 of DMC100 and DMC100F are 9.144 and 6.701 μg/mL in MCF-7, 8.306 and 7.501 μg/mL in KB cell. The fluorescent images revealed that micelles were uptake into KB cells and MCF-7 cells after one hour. Furthermore, flow cytometric analysis was used to assay the different uptake mechanisms and trafficking pathways. The result showed that the 48-57 % DMC100F was in KB cells and 26-39 % in MCF-7 cells inhibited by folic acid, the interaction with expressed folate receptors on the surface of cancer cells. In addition, we found the cellular uptake was 69 % in KB cells and 56 % in MCF-7 reduced by methyl-β-cyclodextrin, an inhibitor of the caveolae-mediated endocytosis pathway. These finding suggest that DMC100F enter cells via multiple pathways and might be a potential carrier for cancer treatment. Ming-Fa Hsieh 謝明發 2012 學位論文 ; thesis 110 zh-TW |
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碩士 === 中原大學 === 生物醫學工程研究所 === 100 === The specificity between normal cells and cancer cells in conventional chemotherapy is in-sufficient. The plasma surface of cancer cells is expressed various receptors depending on the physiological functions of the cells. Folate receptor (FR) is overexpressed in the apical membrane surface of certain cancer cells making a potential target of tumor therapeutics. Hence, in this study, folate-decorated micelles based on the star-shaped PCL-PEG copolymer were prepared for targeting to the folate receptor overexpressing in human oral cavity carcinoma cells (KB) and human breast cancer cells (MCF-7). The structure and molecular weight of micelle materials was characterized by FT-IR and 1H NMR. The of 4SPCL50-PEG-Folate、4SPCL100-PEG-Folate and 4SPCL150-PEG-Folate are 17168、23361 and 28680 g/mol, respectively. The doxorubicin-loaded micelles were prepared using dialysis method (DMC50F、DMC100F、DMC150F). The particle size of the DOX-loaded micelle was 126.2、128.7 and 123.1 nm, respectively. The drug loading efficiency were 76、88.5 and 33.5 %, respectively. The total release of DOX in a period of 60 h at pH 7.4 and 5.4 account for 29 % and 84 % of total DOX concentration loaded; respectively. The IC50 of DMC100 and DMC100F are 9.144 and 6.701 μg/mL in MCF-7, 8.306 and 7.501 μg/mL in KB cell. The fluorescent images revealed that micelles were uptake into KB cells and MCF-7 cells after one hour. Furthermore, flow cytometric analysis was used to assay the different uptake mechanisms and trafficking pathways. The result showed that the 48-57 % DMC100F was in KB cells and 26-39 % in MCF-7 cells inhibited by folic acid, the interaction with expressed folate receptors on the surface of cancer cells. In addition, we found the cellular uptake was 69 % in KB cells and 56 % in MCF-7 reduced by methyl-β-cyclodextrin, an inhibitor of the caveolae-mediated endocytosis pathway. These finding suggest that DMC100F enter cells via multiple pathways and might be a potential carrier for cancer treatment.
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author2 |
Ming-Fa Hsieh |
author_facet |
Ming-Fa Hsieh Yu-Lun Li 李毓倫 |
author |
Yu-Lun Li 李毓倫 |
spellingShingle |
Yu-Lun Li 李毓倫 Tumor Cell Targeting and Endocytosis Pathways of Doxorubicin Loaded Folate-Conjugated Polymeric Micelles |
author_sort |
Yu-Lun Li |
title |
Tumor Cell Targeting and Endocytosis Pathways of Doxorubicin Loaded Folate-Conjugated Polymeric Micelles |
title_short |
Tumor Cell Targeting and Endocytosis Pathways of Doxorubicin Loaded Folate-Conjugated Polymeric Micelles |
title_full |
Tumor Cell Targeting and Endocytosis Pathways of Doxorubicin Loaded Folate-Conjugated Polymeric Micelles |
title_fullStr |
Tumor Cell Targeting and Endocytosis Pathways of Doxorubicin Loaded Folate-Conjugated Polymeric Micelles |
title_full_unstemmed |
Tumor Cell Targeting and Endocytosis Pathways of Doxorubicin Loaded Folate-Conjugated Polymeric Micelles |
title_sort |
tumor cell targeting and endocytosis pathways of doxorubicin loaded folate-conjugated polymeric micelles |
publishDate |
2012 |
url |
http://ndltd.ncl.edu.tw/handle/49896646013671045460 |
work_keys_str_mv |
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