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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 stabilize...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Shenyang Pharmaceutical University
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7032231/ https://www.ncbi.nlm.nih.gov/pubmed/32104484 http://dx.doi.org/10.1016/j.ajps.2018.06.006 |
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author | Han, Xue Su, Ruijuan Huang, Xiuqing Wang, Yingli Kuang, Xiao Zhou, Shuang Liu, Hongzhuo |
author_facet | Han, Xue Su, Ruijuan Huang, Xiuqing Wang, Yingli Kuang, Xiao Zhou, Shuang Liu, Hongzhuo |
author_sort | Han, Xue |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7032231 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Shenyang Pharmaceutical University |
record_format | MEDLINE/PubMed |
spelling | pubmed-70322312020-02-26 Triphenylphosphonium-modified mitochondria-targeted paclitaxel nanocrystals for overcoming multidrug resistance Han, Xue Su, Ruijuan Huang, Xiuqing Wang, Yingli Kuang, Xiao Zhou, Shuang Liu, Hongzhuo Asian J Pharm Sci Original Research Paper 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. Shenyang Pharmaceutical University 2019-09 2018-09-18 /pmc/articles/PMC7032231/ /pubmed/32104484 http://dx.doi.org/10.1016/j.ajps.2018.06.006 Text en © 2018 Published by Elsevier B.V. on behalf of Shenyang Pharmaceutical University. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Paper Han, Xue Su, Ruijuan Huang, Xiuqing Wang, Yingli Kuang, Xiao Zhou, Shuang Liu, Hongzhuo Triphenylphosphonium-modified mitochondria-targeted paclitaxel nanocrystals for overcoming multidrug resistance |
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 |
topic | Original Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7032231/ https://www.ncbi.nlm.nih.gov/pubmed/32104484 http://dx.doi.org/10.1016/j.ajps.2018.06.006 |
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