Triphenylphosphonium-modified mitochondria-targeted paclitaxel nanocrystals for overcoming multidrug resistance
Mitochondria are currently known as novel targets for treating cancer, especially for tumors displaying multidrug resistance (MDR). This present study aimed to develop a mitochondria-targeted delivery system by using triphenylphosphonium cation (TPP+)-conjugated Brij 98 as the functional stabilizer...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-09-01
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| Series: | Asian Journal of Pharmaceutical Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1818087618303982 |
| _version_ | 1828542903131045888 |
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| author | Xue Han Ruijuan Su Xiuqing Huang Yingli Wang Xiao Kuang Shuang Zhou Hongzhuo Liu |
| author_facet | Xue Han Ruijuan Su Xiuqing Huang Yingli Wang Xiao Kuang Shuang Zhou Hongzhuo Liu |
| author_sort | Xue Han |
| collection | DOAJ |
| description | Mitochondria are currently known as novel targets for treating cancer, especially for tumors displaying multidrug resistance (MDR). This present study aimed to develop a mitochondria-targeted delivery system by using triphenylphosphonium cation (TPP+)-conjugated Brij 98 as the functional stabilizer to modify paclitaxel (PTX) nanocrystals (NCs) against drug-resistant cancer cells. Evaluations were performed on 2D monolayer and 3D multicellular spheroids (MCs) of MCF-7 cells and MCF-7/ADR cells. In comparison with free PTX and the non-targeted PTX NCs, the targeted PTX NCs showed the strongest cytotoxicity against both 2D MCF-7 and MCF-7/ADR cells, which was correlated with decreased mitochondrial membrane potential. The targeted PTX NCs exhibited deeper penetration on MCF-7 MCs and more significant growth inhibition on both MCF-7 and MCF-7/ADR MCs. The proposed strategy indicated that the TPP+-modified NCs represent a potentially viable approach for targeted chemotherapeutic molecules to mitochondria. This strategy might provide promising therapeutic outcomes to overcome MDR. Keywords: Paclitaxel, Nanocrystals, Brij 98, Triphenylphosphonium, Multidrug resistance, Mitochondria |
| first_indexed | 2024-12-12T02:04:27Z |
| format | Article |
| id | doaj.art-d4997d950d744fc68a6cd153ed5081d8 |
| institution | Directory Open Access Journal |
| issn | 1818-0876 |
| language | English |
| last_indexed | 2024-12-12T02:04:27Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Asian Journal of Pharmaceutical Sciences |
| spelling | doaj.art-d4997d950d744fc68a6cd153ed5081d82022-12-22T00:42:05ZengElsevierAsian Journal of Pharmaceutical Sciences1818-08762019-09-01145569580Triphenylphosphonium-modified mitochondria-targeted paclitaxel nanocrystals for overcoming multidrug resistanceXue Han0Ruijuan Su1Xiuqing Huang2Yingli Wang3Xiao Kuang4Shuang Zhou5Hongzhuo Liu6Shenyang Pharmaceutical University, Shenyang 110016, ChinaShenyang Pharmaceutical University, Shenyang 110016, ChinaShenyang Pharmaceutical University, Shenyang 110016, ChinaShenyang Pharmaceutical University, Shenyang 110016, ChinaShenyang Pharmaceutical University, Shenyang 110016, ChinaShenyang Pharmaceutical University, Shenyang 110016, ChinaCorresponding author at: Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China. Tel.: +86 24 43520586.; Shenyang Pharmaceutical University, Shenyang 110016, ChinaMitochondria are currently known as novel targets for treating cancer, especially for tumors displaying multidrug resistance (MDR). This present study aimed to develop a mitochondria-targeted delivery system by using triphenylphosphonium cation (TPP+)-conjugated Brij 98 as the functional stabilizer to modify paclitaxel (PTX) nanocrystals (NCs) against drug-resistant cancer cells. Evaluations were performed on 2D monolayer and 3D multicellular spheroids (MCs) of MCF-7 cells and MCF-7/ADR cells. In comparison with free PTX and the non-targeted PTX NCs, the targeted PTX NCs showed the strongest cytotoxicity against both 2D MCF-7 and MCF-7/ADR cells, which was correlated with decreased mitochondrial membrane potential. The targeted PTX NCs exhibited deeper penetration on MCF-7 MCs and more significant growth inhibition on both MCF-7 and MCF-7/ADR MCs. The proposed strategy indicated that the TPP+-modified NCs represent a potentially viable approach for targeted chemotherapeutic molecules to mitochondria. This strategy might provide promising therapeutic outcomes to overcome MDR. Keywords: Paclitaxel, Nanocrystals, Brij 98, Triphenylphosphonium, Multidrug resistance, Mitochondriahttp://www.sciencedirect.com/science/article/pii/S1818087618303982 |
| spellingShingle | Xue Han Ruijuan Su Xiuqing Huang Yingli Wang Xiao Kuang Shuang Zhou Hongzhuo Liu Triphenylphosphonium-modified mitochondria-targeted paclitaxel nanocrystals for overcoming multidrug resistance Asian Journal of Pharmaceutical Sciences |
| title | Triphenylphosphonium-modified mitochondria-targeted paclitaxel nanocrystals for overcoming multidrug resistance |
| title_full | Triphenylphosphonium-modified mitochondria-targeted paclitaxel nanocrystals for overcoming multidrug resistance |
| title_fullStr | Triphenylphosphonium-modified mitochondria-targeted paclitaxel nanocrystals for overcoming multidrug resistance |
| title_full_unstemmed | Triphenylphosphonium-modified mitochondria-targeted paclitaxel nanocrystals for overcoming multidrug resistance |
| title_short | Triphenylphosphonium-modified mitochondria-targeted paclitaxel nanocrystals for overcoming multidrug resistance |
| title_sort | triphenylphosphonium modified mitochondria targeted paclitaxel nanocrystals for overcoming multidrug resistance |
| url | http://www.sciencedirect.com/science/article/pii/S1818087618303982 |
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