Despite the benefits associated with radiotherapy and chemotherapy for glioblastoma (GBM) treatment, most patients experience a relapse following initial therapy. Recurrent or progressive GBM usually does not respond anymore to standard therapy, and this is associated with poor patient outcome. GBM stem cells (GSCs) are a subset of cells resistant to radiotherapy and chemotherapy and play a role in tumor recurrence. The targeting of GSCs and the identification of novel markers are crucial issues in the development of innovative strategies for GBM eradication. By differential cell SELEX (systematic evolution of ligands by exponential enrichment), we have recently described two RNA aptamers, that is, the 40L sequence and its truncated form A40s, able to bind the cell surface of human GSCs. Both aptamers were selective for stem-like growing GBM cells and are rapidly internalized into target cells. In this study, we demonstrate that their binding to cells is mediated by direct recognition of the ephrin type-A receptor 2 (EphA2). Functionally, the two aptamers were able to inhibit cell growth, stemness, and migration of GSCs. Furthermore, A40s was able to cross the blood-brain barrier (BBB) and was stable in serum in in vitro experiments. These results suggest that 40L and A40s represent innovative potential therapeutic tools for GBM.

尽管胶质母细胞瘤（GBM）治疗与放疗和化疗相关，但大多数患者在初始治疗后仍会复发。复发或进行性GBM通常不再对标准疗法产生反应，这与患者预后不良有关。GBM干细胞（GSC）是对放射疗法和化学疗法有抵抗力的细胞的子集，并在肿瘤复发中起作用。GSC的靶向和新标记的鉴定是制定根除GBM创新策略的关键问题。通过差异细胞SELEX（通过指数富集进行配体的系统进化），我们最近描述了两种RNA适体，即40L序列及其截短形式的A40，它们能够结合人GSC的细胞表面。两种适体均对茎样生长的GBM细胞具有选择性，并迅速内化到靶细胞中。在这项研究中，我们证明了它们与细胞的结合是通过直接识别A型ephrin受体2（EphA2）介导的。在功能上，两种适体能够抑制GSC的细胞生长，干性和迁移。此外，A40s能够穿过血脑屏障（BBB），并且在血清中稳定。体外实验。这些结果表明40L和A40s代表了GBM的创新性潜在治疗工具。