Targeted Liposomal Chemotherapies to Treat Triple-Negative Breast Cancer
| Autor: | Lufang Zhou, Ajeet Pal Singh, Jia-Shiung Guan, Yuanxin Xu, Kai Chen, Hanh Giai Ngo, Eddy S. Yang, Qing Wang, Yingnan Si, Ya Zhang, Xiaoguang Margaret Liu |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research combined chemotherapies Mertansine Article Microtubule polymerization 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine targeted liposomes In vivo medicine Doxorubicin Triple-negative breast cancer RC254-282 Taxane business.industry Neoplasms. Tumors. Oncology. Including cancer and carcinogens Gemcitabine 030104 developmental biology Oncology chemistry Paclitaxel 030220 oncology & carcinogenesis Cancer research triple-negative breast cancer business medicine.drug |
| Zdroj: | Cancers Cancers, Vol 13, Iss 3749, p 3749 (2021) Volume 13 Issue 15 |
| ISSN: | 2072-6694 |
| Popis: | Triple-negative breast cancers (TNBCs) are highly aggressive and recurrent. Standard cytotoxic chemotherapies are currently the main treatment options, but their clinical efficacies are limited and patients usually suffer from severe side effects. The goal of this study was to develop and evaluate targeted liposomes-delivered combined chemotherapies to treat TNBCs. Specifically, the IC50 values of the microtubule polymerization inhibitor mertansine (DM1), mitotic spindle assembly defecting taxane (paclitaxel, PTX), DNA synthesis inhibitor gemcitabine (GC), and DNA damage inducer doxorubicin (AC) were tested in both TNBC MDA-MB-231 and MDA-MB-468 cells. Then we constructed the anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) tagged liposomes and confirmed its TNBC cell surface binding using flow cytometry, internalization with confocal laser scanning microscopy, and TNBC xenograft targeting in NSG female mice using In Vivo Imaging System. The safe dosage of anti-EGFR liposomal chemotherapies, i.e., < 20% body weight change, was identified. Finally, the in vivo anti-tumor efficacy studies in TNBC cell line-derived xenograft and patient-derived xenograft models revealed that the targeted delivery of chemotherapies (mertansine and gemcitabine) can effectively inhibit tumor growth. This study demonstrated that the targeted liposomes enable the new formulations of combined therapies that improve anti-TNBC efficacy. |
| Databáze: | OpenAIRE |
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