Reversion of pH-induced physiological drug resistance: a novel function of copolymeric nanoparticles.
AIMS: The extracellular pH of cancer cells is lower than the intracellular pH. Weakly basic anticancer drugs will be protonated extracellularly and display a decreased intracellular concentration. In this study, we show that copolymeric nanoparticles (NPs) are able to overcome this "pH-induced...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3180282?pdf=render |
| _version_ | 1819068132882382848 |
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| author | Rutian Li Li Xie Zhenshu Zhu Qin Liu Yong Hu Xiqun Jiang Lixia Yu Xiaoping Qian Wanhua Guo Yitao Ding Baorui Liu |
| author_facet | Rutian Li Li Xie Zhenshu Zhu Qin Liu Yong Hu Xiqun Jiang Lixia Yu Xiaoping Qian Wanhua Guo Yitao Ding Baorui Liu |
| author_sort | Rutian Li |
| collection | DOAJ |
| description | AIMS: The extracellular pH of cancer cells is lower than the intracellular pH. Weakly basic anticancer drugs will be protonated extracellularly and display a decreased intracellular concentration. In this study, we show that copolymeric nanoparticles (NPs) are able to overcome this "pH-induced physiological drug resistance" (PIPDR) by delivering drugs to the cancer cells via endocytosis rather than passive diffussion. MATERIALS AND METHODS: As a model nanoparticle, Tetradrine (Tet, Pka 7.80) was incorporated into mPEG-PCL. The effectiveness of free Tet and Tet-NPs were compared at different extracellular pHs (pH values 6.8 and 7.4, respectively) by MTT assay, morphological observation and apoptotic analysis in vitro and on a murine model by tumor volume measurement, PET-CT scanning and side effect evaluation in vivo. RESULTS: The cytotoxicity of free Tet decreased prominently (P<0.05) when the extracellular pH decreased from 7.4 to 6.8. Meanwhile, the cytotoxicity of Tet-NPs was not significantly influenced by reduced pH. In vivo experiment also revealed that Tet-NPs reversed PIPDR more effectively than other existing methods and with much less side effects. CONCLUSION: The reversion of PIPDR is a new discovered mechanism of copolymeric NPs. This study emphasized the importance of cancer microenvironmental factors in anticancer drug resistance and revealed the superiority of nanoscale drug carrier from a different aspect. |
| first_indexed | 2024-12-21T16:29:18Z |
| format | Article |
| id | doaj.art-07f9611b5e604b66a4446ec9271ecf29 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T16:29:18Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-07f9611b5e604b66a4446ec9271ecf292022-12-21T18:57:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0169e2417210.1371/journal.pone.0024172Reversion of pH-induced physiological drug resistance: a novel function of copolymeric nanoparticles.Rutian LiLi XieZhenshu ZhuQin LiuYong HuXiqun JiangLixia YuXiaoping QianWanhua GuoYitao DingBaorui LiuAIMS: The extracellular pH of cancer cells is lower than the intracellular pH. Weakly basic anticancer drugs will be protonated extracellularly and display a decreased intracellular concentration. In this study, we show that copolymeric nanoparticles (NPs) are able to overcome this "pH-induced physiological drug resistance" (PIPDR) by delivering drugs to the cancer cells via endocytosis rather than passive diffussion. MATERIALS AND METHODS: As a model nanoparticle, Tetradrine (Tet, Pka 7.80) was incorporated into mPEG-PCL. The effectiveness of free Tet and Tet-NPs were compared at different extracellular pHs (pH values 6.8 and 7.4, respectively) by MTT assay, morphological observation and apoptotic analysis in vitro and on a murine model by tumor volume measurement, PET-CT scanning and side effect evaluation in vivo. RESULTS: The cytotoxicity of free Tet decreased prominently (P<0.05) when the extracellular pH decreased from 7.4 to 6.8. Meanwhile, the cytotoxicity of Tet-NPs was not significantly influenced by reduced pH. In vivo experiment also revealed that Tet-NPs reversed PIPDR more effectively than other existing methods and with much less side effects. CONCLUSION: The reversion of PIPDR is a new discovered mechanism of copolymeric NPs. This study emphasized the importance of cancer microenvironmental factors in anticancer drug resistance and revealed the superiority of nanoscale drug carrier from a different aspect.http://europepmc.org/articles/PMC3180282?pdf=render |
| spellingShingle | Rutian Li Li Xie Zhenshu Zhu Qin Liu Yong Hu Xiqun Jiang Lixia Yu Xiaoping Qian Wanhua Guo Yitao Ding Baorui Liu Reversion of pH-induced physiological drug resistance: a novel function of copolymeric nanoparticles. PLoS ONE |
| title | Reversion of pH-induced physiological drug resistance: a novel function of copolymeric nanoparticles. |
| title_full | Reversion of pH-induced physiological drug resistance: a novel function of copolymeric nanoparticles. |
| title_fullStr | Reversion of pH-induced physiological drug resistance: a novel function of copolymeric nanoparticles. |
| title_full_unstemmed | Reversion of pH-induced physiological drug resistance: a novel function of copolymeric nanoparticles. |
| title_short | Reversion of pH-induced physiological drug resistance: a novel function of copolymeric nanoparticles. |
| title_sort | reversion of ph induced physiological drug resistance a novel function of copolymeric nanoparticles |
| url | http://europepmc.org/articles/PMC3180282?pdf=render |
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