Enhanced therapeutic efficacy of doxorubicin against multidrug-resistant breast cancer with reduced cardiotoxicity
Doxorubicin (DOX), a commonly used anti-cancer drug, is limited by its cardiotoxicity and multidrug resistance (MDR) of tumor cells. Epigallocatechin gallate (EGCG), a natural antioxidant component, can effectively reduce the cardiotoxicity of DOX. Meanwhile, EGCG can inhibit the expression of P-glycoprotein (P-gp) and reverse the MDR of tumor cells. In this study, DOX is connected with low molecular weight polyethyleneimine (PEI) via hydrazone bond to get the pH-sensitive PEI-DOX, which is then combined with EGCG to prevent the cardiotoxicity of DOX and reverse the MDR of cancer cells. In addition, folic acid (FA) modified polyethylene glycol (PEG) (PEG-FA) is added to get the targeted system PEI-DOX/EGCG/FA. The MDR reversal and targeting ability of PEI-DOX/EGCG/FA is performed by cytotoxicity and in vivo anti-tumor activity on multidrug resistant MCF-7 cells (MCF-7/ADR). Additionally, we investigate the anti-drug resistant mechanism by Western Blot. The ability of EGCG to reduce DOX cardiotoxicity is confirmed by cardiotoxicity assay. In conclusion, PEI-DOX/EGCG/FA can inhibit the expression of P-gp and reverse the MDR in tumor cells. It also shows the ability of remove oxygen free radicals effectively to prevent the cardiotoxicity of DOX.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Drug delivery - 30(2023), 1 vom: 15. Dez., Seite 2189118 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Tianyu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.03.2023 Date Revised 22.03.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1080/10717544.2023.2189118 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM354252216 |
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| 245 | 1 | 0 | |a Enhanced therapeutic efficacy of doxorubicin against multidrug-resistant breast cancer with reduced cardiotoxicity |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Doxorubicin (DOX), a commonly used anti-cancer drug, is limited by its cardiotoxicity and multidrug resistance (MDR) of tumor cells. Epigallocatechin gallate (EGCG), a natural antioxidant component, can effectively reduce the cardiotoxicity of DOX. Meanwhile, EGCG can inhibit the expression of P-glycoprotein (P-gp) and reverse the MDR of tumor cells. In this study, DOX is connected with low molecular weight polyethyleneimine (PEI) via hydrazone bond to get the pH-sensitive PEI-DOX, which is then combined with EGCG to prevent the cardiotoxicity of DOX and reverse the MDR of cancer cells. In addition, folic acid (FA) modified polyethylene glycol (PEG) (PEG-FA) is added to get the targeted system PEI-DOX/EGCG/FA. The MDR reversal and targeting ability of PEI-DOX/EGCG/FA is performed by cytotoxicity and in vivo anti-tumor activity on multidrug resistant MCF-7 cells (MCF-7/ADR). Additionally, we investigate the anti-drug resistant mechanism by Western Blot. The ability of EGCG to reduce DOX cardiotoxicity is confirmed by cardiotoxicity assay. In conclusion, PEI-DOX/EGCG/FA can inhibit the expression of P-gp and reverse the MDR in tumor cells. It also shows the ability of remove oxygen free radicals effectively to prevent the cardiotoxicity of DOX | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Li, Nuannuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ru |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Yiying |e verfasserin |4 aut | |
| 700 | 1 | |a He, Xiaoyan |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Xiaoyan |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Liuxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Kaoxiang |e verfasserin |4 aut | |
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