de la Torre Paz, Paris Juan L, Fernández-de la Torre Miguel, Vallet-Regí María, Flores Ana I
Grupo de Medicina Regenerativa, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Avda. Cordoba s/n 28041, 28041 Madrid, Spain.
Departamento de Química en Ciencias Farmacéuticas (Unidad Docente de Química Inorgánica y Bioinorgánica), Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), 28040 Madrid, Spain.
Pharmaceutics. 2021 Feb 10;13(2):244. doi: 10.3390/pharmaceutics13020244.
Combination therapies constitute a powerful tool for cancer treatment. By combining drugs with different mechanisms of action, the limitations of each individual agent can be overcome, while increasing therapeutic benefit. Here, we propose employing tumor-migrating decidua-derived mesenchymal stromal cells as therapeutic agents combining antiangiogenic therapy and chemotherapy. First, a plasmid encoding the antiangiogenic protein endostatin was transfected into these cells by nucleofection, confirming its expression by ELISA and its biological effect in an ex ovo chick embryo model. Second, doxorubicin-loaded mesoporous silica nanoparticles were introduced into the cells, which would act as vehicles for the drug being released. The effect of the drug was evaluated in a coculture in vitro model with mammary cancer cells. Third, the combination of endostatin transfection and doxorubicin-nanoparticle loading was carried out with the decidua mesenchymal stromal cells. This final cell platform was shown to retain its tumor-migration capacity in vitro, and the combined in vitro therapeutic efficacy was confirmed through a 3D spheroid coculture model using both cancer and endothelial cells. The results presented here show great potential for the development of combination therapies based on genetically-engineered cells that can simultaneously act as cellular vehicles for drug-loaded nanoparticles.
联合疗法是癌症治疗的有力工具。通过将具有不同作用机制的药物联合使用，可以克服每种单一药物的局限性，同时提高治疗效果。在此，我们提出利用迁移到肿瘤的蜕膜来源间充质基质细胞作为联合抗血管生成疗法和化疗的治疗剂。首先，通过核转染将编码抗血管生成蛋白内皮抑素的质粒转染到这些细胞中，通过酶联免疫吸附测定法确认其表达，并在鸡胚模型中验证其生物学效应。其次，将负载阿霉素的介孔二氧化硅纳米颗粒导入细胞，这些纳米颗粒将作为药物释放的载体。在与乳腺癌细胞的共培养体外模型中评估药物的效果。第三，对蜕膜间充质基质细胞进行内皮抑素转染和阿霉素纳米颗粒负载的联合操作。这个最终的细胞平台在体外显示出保留其肿瘤迁移能力，并且通过使用癌细胞和内皮细胞的三维球体共培养模型证实了联合体外治疗效果。此处呈现的结果表明，基于基因工程细胞开发联合疗法具有巨大潜力，这些细胞可同时作为负载药物纳米颗粒的细胞载体。
