Rational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant MCF-7 human breast cancer cells
Wei Hong,1 Hong Shi,2 Mingxi Qiao,3 Xiang Gao,1 Jie Yang,1 Chunlian Tian,1 Dexian Zhang,1 Shengli Niu,1 Mingchun Liu11Key Laboratory of Zoonosis of Liaoning, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenhe, Shenyang, Liaoning, 2Department of Pharmaceutics,...
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2017
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/745b1242217d41d8b13ef42109dfbfc9 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:745b1242217d41d8b13ef42109dfbfc9 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:745b1242217d41d8b13ef42109dfbfc92021-12-02T07:46:15ZRational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant MCF-7 human breast cancer cells1178-2013https://doaj.org/article/745b1242217d41d8b13ef42109dfbfc92017-02-01T00:00:00Zhttps://www.dovepress.com/rational-design-of-multifunctional-micelles-against-doxorubicin-sensit-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Wei Hong,1 Hong Shi,2 Mingxi Qiao,3 Xiang Gao,1 Jie Yang,1 Chunlian Tian,1 Dexian Zhang,1 Shengli Niu,1 Mingchun Liu11Key Laboratory of Zoonosis of Liaoning, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenhe, Shenyang, Liaoning, 2Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Jiangning, Nanjing, 3Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, People’s Republic of China Abstract: Even though a tremendous number of multifunctional nanocarriers have been developed to tackle heterogeneous cancer cells, little attention has been paid to elucidate how to rationally design a multifunctional nanocarrier. In this study, three individual functions (active targeting, stimuli-triggered release and endo-lysosomal escape) were evaluated in doxorubicin (DOX)-sensitive MCF-7 cells and DOX-resistant MCF-7/ADR cells by constructing four kinds of micelles with active-targeting (AT-M), passive targeting, pH-triggered release (pHT-M) and endo-lysosomal escape (endoE-M) function, respectively. AT-M demonstrated the strongest cytotoxicity against MCF-7 cells and the highest cellular uptake of DOX due to the folate-mediated endocytosis. However, AT-M failed to exhibit the best efficacy against MCF-7/ADR cells, while endoE-M exhibited the strongest cytotoxicity against MCF-7/ADR cells and the highest cellular uptake of DOX due to the lowest elimination of DOX from the cells. This was attributed to the carrier-facilitated endo-lysosomal escape of DOX, which avoided exocytosis by lysosome secretion, resulting in an effective accumulation of DOX in the cytoplasm. The enhanced elimination of DOX from the MCF-7/ADR cells also accounted for the remarkable decrease in cytotoxicity against the cells of AT-M. Three micelles were further evaluated with MCF-7 cells and MCF-7/ADR-resistant cells xenografted mice model. In accordance with the in vitro results, AT-M and endoE-M demonstrated the strongest inhibition on the MCF-7 and MCF-7/ADR xenografted tumor, respectively. Active targeting and active targeting in combination with endo-lysosomal escape have been demonstrated to be the primary function for a nanocarrier against doxorubicin-sensitive and doxorubicin-resistant MCF-7 cells, respectively. These results indicate that the rational design of multifunctional nanocarriers for cancer therapy needs to consider the heterogeneous cancer cells and the primary function needs to be integrated to achieve effective payload delivery.Keywords: rational design, multidrug resistance, active targeting, pH-triggered release, endo-lysosomal escape Hong WShi HQiao MGao XYang JTian CZhang DNiu SLiu MDove Medical Pressarticlemultifunctional micellesmultidrug resistanceactive targetingpH-triggered releaseendo-lysosomal escape.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 989-1007 (2017) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
multifunctional micelles multidrug resistance active targeting pH-triggered release endo-lysosomal escape. Medicine (General) R5-920 |
| spellingShingle |
multifunctional micelles multidrug resistance active targeting pH-triggered release endo-lysosomal escape. Medicine (General) R5-920 Hong W Shi H Qiao M Gao X Yang J Tian C Zhang D Niu S Liu M Rational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant MCF-7 human breast cancer cells |
| description |
Wei Hong,1 Hong Shi,2 Mingxi Qiao,3 Xiang Gao,1 Jie Yang,1 Chunlian Tian,1 Dexian Zhang,1 Shengli Niu,1 Mingchun Liu11Key Laboratory of Zoonosis of Liaoning, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenhe, Shenyang, Liaoning, 2Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Jiangning, Nanjing, 3Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, People’s Republic of China Abstract: Even though a tremendous number of multifunctional nanocarriers have been developed to tackle heterogeneous cancer cells, little attention has been paid to elucidate how to rationally design a multifunctional nanocarrier. In this study, three individual functions (active targeting, stimuli-triggered release and endo-lysosomal escape) were evaluated in doxorubicin (DOX)-sensitive MCF-7 cells and DOX-resistant MCF-7/ADR cells by constructing four kinds of micelles with active-targeting (AT-M), passive targeting, pH-triggered release (pHT-M) and endo-lysosomal escape (endoE-M) function, respectively. AT-M demonstrated the strongest cytotoxicity against MCF-7 cells and the highest cellular uptake of DOX due to the folate-mediated endocytosis. However, AT-M failed to exhibit the best efficacy against MCF-7/ADR cells, while endoE-M exhibited the strongest cytotoxicity against MCF-7/ADR cells and the highest cellular uptake of DOX due to the lowest elimination of DOX from the cells. This was attributed to the carrier-facilitated endo-lysosomal escape of DOX, which avoided exocytosis by lysosome secretion, resulting in an effective accumulation of DOX in the cytoplasm. The enhanced elimination of DOX from the MCF-7/ADR cells also accounted for the remarkable decrease in cytotoxicity against the cells of AT-M. Three micelles were further evaluated with MCF-7 cells and MCF-7/ADR-resistant cells xenografted mice model. In accordance with the in vitro results, AT-M and endoE-M demonstrated the strongest inhibition on the MCF-7 and MCF-7/ADR xenografted tumor, respectively. Active targeting and active targeting in combination with endo-lysosomal escape have been demonstrated to be the primary function for a nanocarrier against doxorubicin-sensitive and doxorubicin-resistant MCF-7 cells, respectively. These results indicate that the rational design of multifunctional nanocarriers for cancer therapy needs to consider the heterogeneous cancer cells and the primary function needs to be integrated to achieve effective payload delivery.Keywords: rational design, multidrug resistance, active targeting, pH-triggered release, endo-lysosomal escape |
| format |
article |
| author |
Hong W Shi H Qiao M Gao X Yang J Tian C Zhang D Niu S Liu M |
| author_facet |
Hong W Shi H Qiao M Gao X Yang J Tian C Zhang D Niu S Liu M |
| author_sort |
Hong W |
| title |
Rational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant MCF-7 human breast cancer cells |
| title_short |
Rational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant MCF-7 human breast cancer cells |
| title_full |
Rational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant MCF-7 human breast cancer cells |
| title_fullStr |
Rational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant MCF-7 human breast cancer cells |
| title_full_unstemmed |
Rational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant MCF-7 human breast cancer cells |
| title_sort |
rational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant mcf-7 human breast cancer cells |
| publisher |
Dove Medical Press |
| publishDate |
2017 |
| url |
https://doaj.org/article/745b1242217d41d8b13ef42109dfbfc9 |
| work_keys_str_mv |
AT hongw rationaldesignofmultifunctionalmicellesagainstdoxorubicinsensitiveanddoxorubicinresistantmcf7humanbreastcancercells AT shih rationaldesignofmultifunctionalmicellesagainstdoxorubicinsensitiveanddoxorubicinresistantmcf7humanbreastcancercells AT qiaom rationaldesignofmultifunctionalmicellesagainstdoxorubicinsensitiveanddoxorubicinresistantmcf7humanbreastcancercells AT gaox rationaldesignofmultifunctionalmicellesagainstdoxorubicinsensitiveanddoxorubicinresistantmcf7humanbreastcancercells AT yangj rationaldesignofmultifunctionalmicellesagainstdoxorubicinsensitiveanddoxorubicinresistantmcf7humanbreastcancercells AT tianc rationaldesignofmultifunctionalmicellesagainstdoxorubicinsensitiveanddoxorubicinresistantmcf7humanbreastcancercells AT zhangd rationaldesignofmultifunctionalmicellesagainstdoxorubicinsensitiveanddoxorubicinresistantmcf7humanbreastcancercells AT nius rationaldesignofmultifunctionalmicellesagainstdoxorubicinsensitiveanddoxorubicinresistantmcf7humanbreastcancercells AT lium rationaldesignofmultifunctionalmicellesagainstdoxorubicinsensitiveanddoxorubicinresistantmcf7humanbreastcancercells |
| _version_ |
1718399163182350336 |