原文献：Hypoxia Engineered Bone Marrow Mesenchymal Stem Cells Targeting System with Tumor Microenvironment Regulation for Enhanced Chemotherapy of Breast Cancer

文献链接：

https://pubmed.ncbi.nlm.nih.gov/34069607/

作者：Jingzhi Zu , Liwei Tan, Li Yang , Qi Wang , Jing Qin , Jing Peng , Hezhong Jiang, Rui Tan  

and Jian Gu

摘要：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@HbMSCs) with tumor-targeting ability was constructed according to the uptake of DTX-M by hypoxiainduced 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.

两亲性嵌段共聚物mPEG-PLGA是一种良好的胶束载体，可以提高疏水化合物在水中的分散性，延长其内循环时间。因此，研究选择mPEG-PLGA形成DTX胶束，并表现出较好的稳定性和载化合物能力。采用薄膜水化法制备了DTX胶束。具体制备方式如下：

DTX-M采用薄膜水化法制备，以Sn（Oct）2为催化剂，将ε-乳酸和ε-乙醇酸在mPEG上开环聚合合成。首先，将DTX和mPEG-PLGA共溶于一个圆底烧瓶中的脱水酒精中。溶剂在旋转器蒸发器中混合蒸发，并形成一层薄薄的均匀薄膜。将混合物与生理盐水适度摇晃下水合。在这种情况下，两亲性共聚物自组装成胶封DTX的胶束，并通过0.22µm注射器过滤器过滤。用生理盐水重建冻干胶束，在适当的温度下进行温和搅拌，重新溶解DTX胶束。

图1：DTX-M的制备和表征

结论：如图1A所示，DTX-M清晰透明，溶液呈淡蓝色，呈乳白色。与水相比，在DTX-M中出现了明显的廷德尔效应。DTX-M和黑色胶束的平均粒径约为30nm（图1B）。根据低轴诱导的H-bMSCs摄取DTX-M，构建了具有tumor靶向能力的干细胞Chemotherapy 复合物系统（DTX@HbMSCs）。以mPEG-PLGA为原料参与制备的DTX胶束提高了H-b间充质干细胞对DTX的吸收效率，使DTX@H-b间充质干细胞具有良好的载化合物量和稳定性。