Ratiometric co-delivery of doxorubicin and docetaxel by covalently conjugating with mPEG-poly(β-malic acid) for enhanced synergistic breast tumor therapy
| العنوان: | Ratiometric co-delivery of doxorubicin and docetaxel by covalently conjugating with mPEG-poly(β-malic acid) for enhanced synergistic breast tumor therapy |
|---|---|
| المؤلفون: | Zhe Yu, Hua Li, Shibin Yu, Chaoli Wang, Hong Wu, Tiehong Yang, Yiyang Jia, Xin He, Qing Zhou, Youbei Qiao |
| المصدر: | Polymer Chemistry. 11:7330-7339 |
| بيانات النشر: | Royal Society of Chemistry (RSC), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Drug, Polymers and Plastics, Chemistry, media_common.quotation_subject, Organic Chemistry, Bioengineering, Combination chemotherapy, 02 engineering and technology, Pharmacology, 021001 nanoscience & nanotechnology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Therapeutic index, Pharmacokinetics, Docetaxel, In vivo, 030220 oncology & carcinogenesis, medicine, Doxorubicin, 0210 nano-technology, IC50, medicine.drug, media_common |
| الوصف: | Codelivery of chemotherapeutic drugs using polymer–drug carriers represents a promising strategy to achieve ratiometric delivery and a synergistic effect in targeted tissues and cells, which will improve the therapeutic index and reduce the side effects as compared to traditional cancer combination chemotherapy. In this study, a novel biodegradable methoxy poly(ethylene glycol)-poly(β-malic acid) (mPEG-PLMA) nanoparticle is developed for the precise codelivery of two established drugs (doxorubicin and docetaxel) and hypothesized to act synergistically to improve the anticancer efficacy of the two drugs. Doxorubicin (DOX) and docetaxel (DTX) were covalently bound to mPEG-PMLA through a one-step coupling reaction with distinct linkers, resulting in mPEG-PMLA-DOX/DTX conjugates. The conjugates exhibited a significant synergistic inhibitory effect on human breast cancer cells MDA-MB-231 when the molar ratio of conjugated DOX/DTX was 1 : 1, with an IC50 value of about 0.62 μg mL−1 for DOX and 0.91 μg mL−1 for DTX, only accounting for 40% and 7% of the IC50 for free DOX and DTX, respectively. The results of the pharmacokinetic study show that the conjugates were capable of increasing the half-life (DOX with 1.7-fold and DTX with 3.3-fold) and AUC (DOX with 2.2-fold and DTX with 4.5-fold) and maintaining the synergistic drug ratio at the tumor site for over 24 h. Furthermore, the conjugate displayed more potent anti-tumor efficacy and lower systemic toxicity than the free drug combination in vivo. These results confirmed that the combinatorial delivery system could exhibit a fascinating prospect for the synergistic delivery of drugs with diverse physicochemical properties in cancer treatment integrating efficiency and safety considerations. |
| تدمد: | 1759-9962 1759-9954 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::b1a21c4d3833715418e6322e06a1b4ca https://doi.org/10.1039/d0py01130d |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........b1a21c4d3833715418e6322e06a1b4ca |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17599962 17599954 |
|---|