LUNAM Université, Ingénierie de la Vectorisation Particulaire, F-49933 Angers, France.
Int J Pharm. 2012 Feb 14;423(1):63-8. doi: 10.1016/j.ijpharm.2011.04.058. Epub 2011 Apr 30.
The prognosis of patients with malignant glioma remains extremely poor despite surgery and improvements in radio- and chemo-therapies. Thus, treatment strategies that specifically target these tumors have the potential to greatly improve therapeutic outcomes. "Marrow-isolated adult multilineage inducible" cells (MIAMI cells) are a subpopulation of mesenchymal stromal cells (MSCs) which possess the ability to migrate to brain tumors. We have previously shown that MIAMI cells were able to efficiently incorporate lipid nanocapsules (LNCs) without altering either their stem cell properties or their migration capacity. In this study, we assessed whether the cytotoxic effects of MIAMI cells loaded with LNCs containing an organometallic complex (ferrociphenol or Fc-diOH) could be used to treat brain tumors. The results showed that MIAMI cells internalized Fc-diOH-LNCs and that this internalization did not induce MIAMI cell death. Furthermore, Fc-diOH-LNC-loaded MIAMI cells produced a cytotoxic effect on U87MG glioma cells in vitro. This cytotoxic effect was validated in vivo after intratumoral injection of Fc-diOH-LNC-loaded MIAMI cells in a heterotopic U87MG glioma model in nude mice. These promising results open up a new field of treatment in which cellular vehicles and nanoparticles can be combined to treat brain tumors.
尽管手术和放射治疗及化疗的改进，恶性脑胶质瘤患者的预后仍然极差。因此，专门针对这些肿瘤的治疗策略有可能极大地改善治疗效果。“骨髓分离的成年多谱系诱导”细胞（MIAMI 细胞）是间充质基质细胞（MSCs）的一个亚群，具有迁移到脑肿瘤的能力。我们之前已经表明，MIAMI 细胞能够有效地摄取脂质纳米胶囊（LNC），而不会改变其干细胞特性或迁移能力。在这项研究中，我们评估了负载含有金属有机配合物（ferrociphenol 或 Fc-diOH）的 LNC 的 MIAMI 细胞的细胞毒性作用是否可用于治疗脑肿瘤。结果表明，MIAMI 细胞内化了 Fc-diOH-LNC，并且这种内化不会诱导 MIAMI 细胞死亡。此外，负载 Fc-diOH-LNC 的 MIAMI 细胞在体外对 U87MG 神经胶质瘤细胞产生细胞毒性作用。在裸鼠的异位 U87MG 神经胶质瘤模型中，经瘤内注射负载 Fc-diOH-LNC 的 MIAMI 细胞后，验证了这种细胞毒性作用。这些有希望的结果开辟了一个新的治疗领域，其中细胞载体和纳米颗粒可以结合起来治疗脑肿瘤。
