Co-delivery of doxorubicin and conferone by novel pH-responsive β-cyclodextrin grafted micelles triggers apoptosis of metastatic human breast cancer cells
Abstract Adjuvant-aided combination chemotherapy is one of the most effective ways of cancer treatment by overcoming the multidrug resistance (MDR) and reducing the side-effects of anticancer drugs. In this study, Conferone (Conf) was used as an adjuvant in combination with Doxorubicin (Dox) for ind...
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| Autores principales: | , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/2ae2574e1aa34cacb415e88f73f4b570 |
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| Sumario: | Abstract Adjuvant-aided combination chemotherapy is one of the most effective ways of cancer treatment by overcoming the multidrug resistance (MDR) and reducing the side-effects of anticancer drugs. In this study, Conferone (Conf) was used as an adjuvant in combination with Doxorubicin (Dox) for inducing apoptosis to MDA-MB-231 cells. Herein, the novel biodegradable amphiphilic β-cyclodextrin grafted poly maleate-co-PLGA was synthesized by thiol-ene addition and ring-opening process. Micelles obtained from the novel copolymer showed exceptional properties such as small size of around 34.5 nm, CMC of 0.1 μg/mL, and cell internalization of around 100% at 30 min. These novel engineered micelles were used for combination delivery of doxorubicin-conferone with high encapsulation efficiency of near 100% for both drugs. Our results show that combination delivery of Dox and Conf to MDA-MB-231 cells had synergistic effects (CI < 1). According to cell cycle and Annexin-V apoptosis analysis, Dox-Conf loaded micelle significantly induce tumor cell apoptosis (more than 98% of cells population showed apoptosis at IC 50 = 0.259 μg/mL). RT-PCR and western-blot tests show that Dox-Conf loaded βCD-g-PMA-co-PLGA micelle induced apoptosis via intrinsic pathway. Therefore, the unique design of multi-functional pH-sensitive micelles open a new perspective for the development of nanomedicine for combination chemo-adjuvant therapy against malignant cancer. |
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