Biomedical Research Foundation Academy of Athens, Athens, 11527, Greece.
Department of Informatics and Telecommunications, Postgraduate Program: 'Information Technologies in Medicine and Biology', University of Athens, Athens, 15784, Greece.
Sci Rep. 2017 Apr 10;7(1):775. doi: 10.1038/s41598-017-00836-y.
Therapeutic targeting of tumor cells with drug nanocarriers relies upon successful interaction with membranes and efficient cell internalization. A further consideration is that engineered nanomaterials should not damage healthy tissues upon contact. A critical factor in this process is the external coating of drug delivery nanodevices. Using in silico, in vitro and in vivo studies, we show for the first time that magnetic nanoparticles coated with polyarabic acid have superior imaging, therapeutic, and biocompatibility properties. We demonstrate that polyarabic acid coating allows for efficient penetration of cell membranes and internalization into breast cancer cells. Polyarabic acid also allows reversible loading of the chemotherapeutic drug Doxorubicin, which upon release suppresses tumor growth in vivo in a mouse model of breast cancer. Furthermore, these nanomaterials provide in vivo contrasting properties, which directly compare with commercial gadolinium-based contrasting agents. Finally, we report excellent biocompatibility, as these nanomaterial cause minimal, if any cytotoxicity in vitro and in vivo. We thus propose that magnetic nanodevices coated with polyarabic acid offer a new avenue for theranostics efforts as efficient drug carriers, while providing excellent contrasting properties due to their ferrous magnetic core, which can help the future design of nanomaterials for cancer imaging and therapy.
用药物纳米载体对肿瘤细胞进行治疗性靶向依赖于与细胞膜的成功相互作用和有效的细胞内化。另一个需要考虑的因素是,工程纳米材料在接触时不应损伤健康组织。在这个过程中,一个关键因素是药物递送纳米器件的外部涂层。通过计算机模拟、体外和体内研究,我们首次表明,用聚阿拉伯酸包覆的磁性纳米颗粒具有优越的成像、治疗和生物相容性。我们证明了聚阿拉伯酸涂层允许有效地穿透细胞膜并进入乳腺癌细胞内化。聚阿拉伯酸还允许可逆装载化疗药物阿霉素,在乳腺癌小鼠模型中,阿霉素的释放抑制了肿瘤生长。此外,这些纳米材料提供了体内对比特性,可直接与商业基于钆的对比剂进行比较。最后,我们报告了极好的生物相容性,因为这些纳米材料在体外和体内引起的细胞毒性最小(如果有的话)。因此,我们提出,用聚阿拉伯酸包覆的磁性纳米器件为作为有效的药物载体的治疗学努力提供了新途径,同时由于其亚铁磁核提供了优异的对比特性,这有助于未来设计用于癌症成像和治疗的纳米材料。