| Autor: |
Sifeng Zhu, Chao Sun, Zimin Cai, Yunyan Li, Wendian Liu, Yun Luan, Cheng Wang |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Materials Today Bio, Vol 26, Iss , Pp 101029- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2590-0064 |
| DOI: |
10.1016/j.mtbio.2024.101029 |
| Popis: |
Multi-drug resistance (MDR) in advanced breast cancer (ABC) is triggered by the high expression of P-glycoprotein (P-gp), which reduces intracellular concentration of anti-tumor drugs, in turn preventing oxidative stress damage to cytoplasmic and mitochondrial membranes. It is therefore of clinical relevance to develop P-gp-specific targeted nanocarriers for the treatment of drug resistant ABC. Herein, a drug carrier targeting CD44 and mitochondria was synthesised for the delivery of encequidar (ER, P-gp inhibitor) and paclitaxel (PTX). HT@ER/PTX nanoparticles (ER:PTX molar ratio 1:1) had excellent P-gp inhibition ability and targeted mitochondria to induce apoptosis in MCF-7/PTX cells in vitro. Furthermore, HT@ER/PTX nanocarriers showed more anti-tumor efficacy than PTX (Taxol®) in a xenograft mouse model of MCF-7/PTX cells; the tumor inhibitory rates of HT@ER/PTX nanoparticles and Taxol® were 72.64% ± 4.41% and 32.36% ± 4.09%, respectively. The survival of tumor-bearing mice administered HT@ER/PTX nanoparticles was prolonged compared to that of the mice treated with Taxol®. In addition, HT@ER/PTX not only inhibited P-gp-mediated removal of toxic lipid peroxidation byproducts resulting from anti-tumor drugs but also upregulated the expression of mitochondrial dynamics-related protein, fostering oxidative stress damage, which induced activation of the Caspase-3 apoptosis pathway. Our findings indicate that mitochondria targeted co-delivery of anti-tumor drugs and P-gp inhibitors could be a practical approach in treating multi-drug resistance in ABC. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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