Graduate Program of Biomedical Engineering, University of Manitoba, Winnipeg, MB, Canada.
Department of Biosystems Engineering, Faculty of Agricultural and Food Sciences, University of Manitoba, Winnipeg, MB, Canada.
Sci Rep. 2018 Jun 20;8(1):9377. doi: 10.1038/s41598-018-27733-2.
Salinomycin is an antibiotic that has recently been introduced as a novel and effective anti-cancer drug. In this study, PLGA nanofibers (NFs) containing salinomycin (Sali) were fabricated by electrospinning for the first time. The biodegradable PLGA NFs had stability for approximately 30 days and exhibited a sustained release of the drug for at least a 2-week period. Cytotoxicity of the NFs + Sali was evaluated on human glioblastoma U-251 cells and more than 50% of the treated cells showed apoptosis in 48 h. Moreover, NFs + Sali was effective to induce intracellular reactive oxygen species (ROS) leading to cell apoptosis. Gene expression studies also revealed the capability of the NFs + Sali to upregulate tumor suppressor Rbl1 and Rbl2 as well as Caspase 3 while decreasing Wnt signaling pathway. In general, the results indicated anti-tumor activity of the Sali-loaded NFs suggesting their potential applications as implantable drug delivery systems in the brain upon surgical resection of the tumor.
沙利霉素是一种新型有效的抗癌药物,最近被引入。本研究首次通过静电纺丝制备了载有沙利霉素(Sali)的可生物降解的 PLGA 纳米纤维(NFs)。PLGA NFs 大约稳定 30 天,并表现出至少 2 周的药物持续释放。NFs+Sali 对人神经胶质瘤 U-251 细胞的细胞毒性进行了评估,48 h 后超过 50%的处理细胞显示凋亡。此外,NFs+Sali 能够有效地诱导细胞内活性氧(ROS),导致细胞凋亡。基因表达研究还表明,NFs+Sali 能够上调肿瘤抑制基因 Rbl1 和 Rbl2 以及 Caspase 3,同时降低 Wnt 信号通路。总的来说,结果表明载 Sali 的 NFs 具有抗肿瘤活性,提示其在肿瘤切除手术后作为可植入药物输送系统在大脑中的潜在应用。