Combating multidrug resistance of breast cancer with ginsenoside Rh2-irrigated nano-in-thermogel
Copyright © 2023 Elsevier B.V. All rights reserved..
The emergence of multidrug resistance (MDR) is the leading cause of mortality in patients with breast cancer. Overexpressed P-glycoprotein (P-gp) that can pump out chemotherapeutics from multidrug-resistant cancer cells is the main cause of chemotherapy failure. P-gp inhibitors are hence increasingly used to sensitize chemotherapy to breast cancer with MDR by reducing the efflux of drugs. However, representative P-gp inhibitors usually have severe side effects and the effect of their release behavior on chemotherapy are neglected in current studies. We constructed a nano-in-thermogel delivery system with the sequential release of ginsenoside Rh2 (GRh2) and a chemotherapeutic drug in the tumor microenvironment as a drug compounding "reservoir" to combat MDR in breast cancer. Briefly, paclitaxel (PTX) and GRh2 were encapsulated in solid lipid nanoparticles (SLNs) and dispersed in a poloxamer-based thermogel (SLNs-Gel). GRh2 was used as an innovative and safe P-gp inhibitor to lower P-gp expression and cellular adenosine triphosphate context, thereby sensitizing PTX-resistant breast cancer cells (MCF-7/PTX) to PTX. Pharmacodynamic and in vivo safety studies confirmed that intratumoral injection of SLNs-Gel significantly suppressed the proliferation of PTX-resistant breast cancer and alleviated the PTX-induced hematotoxicity. The GRh2-irrigated nano-in-thermogel delivery system shows great potential in combating multidrug-resistant cancer.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:650 |
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| Enthalten in: |
International journal of pharmaceutics - 650(2024) vom: 25. Jan., Seite 123718 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Long, Jieyu [VerfasserIn] |
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| Links: |
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| Themen: |
20(S)-ginsenoside Rh2 |
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| Anmerkungen: |
Date Completed 08.01.2024 Date Revised 08.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijpharm.2023.123718 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a The emergence of multidrug resistance (MDR) is the leading cause of mortality in patients with breast cancer. Overexpressed P-glycoprotein (P-gp) that can pump out chemotherapeutics from multidrug-resistant cancer cells is the main cause of chemotherapy failure. P-gp inhibitors are hence increasingly used to sensitize chemotherapy to breast cancer with MDR by reducing the efflux of drugs. However, representative P-gp inhibitors usually have severe side effects and the effect of their release behavior on chemotherapy are neglected in current studies. We constructed a nano-in-thermogel delivery system with the sequential release of ginsenoside Rh2 (GRh2) and a chemotherapeutic drug in the tumor microenvironment as a drug compounding "reservoir" to combat MDR in breast cancer. Briefly, paclitaxel (PTX) and GRh2 were encapsulated in solid lipid nanoparticles (SLNs) and dispersed in a poloxamer-based thermogel (SLNs-Gel). GRh2 was used as an innovative and safe P-gp inhibitor to lower P-gp expression and cellular adenosine triphosphate context, thereby sensitizing PTX-resistant breast cancer cells (MCF-7/PTX) to PTX. Pharmacodynamic and in vivo safety studies confirmed that intratumoral injection of SLNs-Gel significantly suppressed the proliferation of PTX-resistant breast cancer and alleviated the PTX-induced hematotoxicity. The GRh2-irrigated nano-in-thermogel delivery system shows great potential in combating multidrug-resistant cancer | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 20(S)-ginsenoside Rh2 | |
| 650 | 4 | |a Multidrug-resistant breast cancer | |
| 650 | 4 | |a Nano-in-thermogel delivery system | |
| 650 | 4 | |a P-glycoprotein | |
| 650 | 4 | |a Paclitaxel | |
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| 700 | 1 | |a Hu, Wanshan |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xuewen |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Chuanbin |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Tingting |e verfasserin |4 aut | |
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