Enzyme/pH dual stimuli-responsive nanoplatform co-deliver disulfiram and doxorubicin for effective treatment of breast cancer lung metastasis
OBJECTIVES: Metastasis is still one of the main obstacles in the treatment of breast cancer. This study aimed to develop disulfiram (DSF) and doxorubicin (DOX) co-loaded nanoparticles (DSF-DOX NPs) with enzyme/pH dual stimuli-responsive characteristics to inhibit breast cancer metastasis.
METHODS: DSF-DOX NPs were prepared using the amphiphilic poly(ε-caprolactone)-b-poly(L-glutamic acid)-g-methoxy poly(ethylene glycol) (PCL-b-PGlu-g-mPEG) copolymer by a classical dialysis method. In vitro release tests, in vitro cytotoxicity assay, and anti-metastasis studies were conducted to evaluate pH/enzyme sensitivity and therapeutic effect of DSF-DOX NPs.
RESULTS: The specific pH and enzyme stimuli-responsiveness of DSF-DO NPs can be attributed to the transformation of secondary structure and the degradation of amide bonds in the PGlu segment, respectively. This accelerated drug release significantly increased the cytotoxicity to 4T1 cells. Compared with the control group, the DSF-DOX NPs showed a strong inhibition of in vitro metastasis with a wound healing rate of 36.50% and a migration rate of 18.39%. Impressively, in vivo anti-metastasis results indicated that the metastasis of 4T1 cells was almost completely suppressed by DSF-DOX NPs.
CONCLUSION: DSF-DOX NPs with controllable tumor site delivery of DOX and DSF were a prospectively potential strategy for metastatic breast cancer treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
Expert opinion on drug delivery - 20(2023), 7 vom: 15. Juli, Seite 1015-1031 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xiao, Peifu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.11.2023 Date Revised 02.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/17425247.2023.2237888 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM359534414 |
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| 100 | 1 | |a Xiao, Peifu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Enzyme/pH dual stimuli-responsive nanoplatform co-deliver disulfiram and doxorubicin for effective treatment of breast cancer lung metastasis |
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| 500 | |a Date Completed 02.11.2023 | ||
| 500 | |a Date Revised 02.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVES: Metastasis is still one of the main obstacles in the treatment of breast cancer. This study aimed to develop disulfiram (DSF) and doxorubicin (DOX) co-loaded nanoparticles (DSF-DOX NPs) with enzyme/pH dual stimuli-responsive characteristics to inhibit breast cancer metastasis | ||
| 520 | |a METHODS: DSF-DOX NPs were prepared using the amphiphilic poly(ε-caprolactone)-b-poly(L-glutamic acid)-g-methoxy poly(ethylene glycol) (PCL-b-PGlu-g-mPEG) copolymer by a classical dialysis method. In vitro release tests, in vitro cytotoxicity assay, and anti-metastasis studies were conducted to evaluate pH/enzyme sensitivity and therapeutic effect of DSF-DOX NPs | ||
| 520 | |a RESULTS: The specific pH and enzyme stimuli-responsiveness of DSF-DO NPs can be attributed to the transformation of secondary structure and the degradation of amide bonds in the PGlu segment, respectively. This accelerated drug release significantly increased the cytotoxicity to 4T1 cells. Compared with the control group, the DSF-DOX NPs showed a strong inhibition of in vitro metastasis with a wound healing rate of 36.50% and a migration rate of 18.39%. Impressively, in vivo anti-metastasis results indicated that the metastasis of 4T1 cells was almost completely suppressed by DSF-DOX NPs | ||
| 520 | |a CONCLUSION: DSF-DOX NPs with controllable tumor site delivery of DOX and DSF were a prospectively potential strategy for metastatic breast cancer treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Breast cancer metastasis | |
| 650 | 4 | |a PCL-b-PGlu-g-mPEG | |
| 650 | 4 | |a disulfiram | |
| 650 | 4 | |a doxorubicin | |
| 650 | 4 | |a enzyme/pH dual-responsive | |
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| 700 | 1 | |a Tao, Xiaoguang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hanxun |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hongbing |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Yupeng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Yueqi |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Zhengzhen |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Tian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a He, Haibing |e verfasserin |4 aut | |
| 700 | 1 | |a Gou, Jingxin |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Xing |e verfasserin |4 aut | |
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