Zu Jingzhi, Tan Liwei, Yang Li, Wang Qi, Qin Jing, Peng Jing, Jiang Hezhong, Tan Rui, Gu Jian
College of Medicine, Southwest Jiaotong University, Chengdu 610031, China.
College of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Biomedicines. 2021 May 19;9(5):575. doi: 10.3390/biomedicines9050575.
Improving the tumor targeting of docetaxel (DTX) would not only be favored for the chemotherapeutic efficacy, but also reduce its side effects. However, the regulation of the tumor microenvironment could further inhibit the growth of tumors. In this study, we introduced a system consisting of hypoxia-engineered bone marrow mesenchymal stem cells (H-bMSCs) and DTX micelles (DTX-M) for breast cancer treatment. First, the stem cell chemotherapy complex system (DTX@H-bMSCs) with tumor-targeting ability was constructed according to the uptake of DTX-M by hypoxia-induced bMSCs (H-bMSCs). DTX micellization improved the uptake efficiency of DTX by H-bMSCs, which equipped DTX@H-bMSCs with satisfactory drug loading and stability. Furthermore, the migration of DTX@H-bMSCs revealed that it could effectively target the tumor site and facilitate the drug transport between cells. Moreover, in vitro and in vivo pharmacodynamics of DTX@H-bMSCs exhibited a superior antitumor effect, which could promote the apoptosis of 4T1 cells and upregulate the expression of inflammatory factors at the tumor site. In brief, DTX@H-bMSCs enhanced the chemotherapeutic effect in breast cancer treatment.
提高多西他赛（DTX）的肿瘤靶向性不仅有利于提高化疗疗效，还能降低其副作用。然而，肿瘤微环境的调节可进一步抑制肿瘤生长。在本研究中，我们引入了一种由缺氧工程化骨髓间充质干细胞（H-bMSCs）和DTX胶束（DTX-M）组成的系统用于乳腺癌治疗。首先，根据缺氧诱导的骨髓间充质干细胞（H-bMSCs）对DTX-M的摄取，构建了具有肿瘤靶向能力的干细胞化疗复合系统（DTX@H-bMSCs）。DTX胶束化提高了H-bMSCs对DTX的摄取效率，使DTX@H-bMSCs具有令人满意的载药量和稳定性。此外，DTX@H-bMSCs的迁移表明它可以有效地靶向肿瘤部位并促进细胞间的药物转运。而且，DTX@H-bMSCs的体外和体内药效学表现出优异的抗肿瘤作用，可促进4T1细胞凋亡并上调肿瘤部位炎症因子的表达。简而言之，DTX@H-bMSCs增强了乳腺癌治疗中的化疗效果。
