Glioblastoma multiforme (GBM) is the most prevalent and lethal malignant intracranial tumor in the brain, with very poor prognosis and survival. The epidermal growth factor receptor variant III (EGFRvIII) contributes to increased oncogenicity that does not occur through binding EGFR ligands and instead occurs through constitutive activation, which enhances glioma tumorigenicity and resistance to targeted therapy. Aptamers are nucleic acids with high affinity and specificity to targets selected by systematic evolution of ligands by exponential enrichment (SELEX), and are usually developed as antagonists of disease-associated factors. Herein, we generated a DNA aptamer U2, targeting U87-EGFRvIII cells, and demonstrated that U2 alters the U87-EGFRvIII cell growth, radiosensitivity, and radiotherapy of glioblastoma cells. We detected U2 and U87-EGFRvIII cells by flow cytometry and confocal microscopy to explore the binding ability of U2 to U87-EGFRvIII cells. Then, we found that aptamer U2 inhibits the proliferation, migration, invasion, and downstream signaling of U87-EGFRvIII cells. Moreover, the U2 aptamer can increase the radiosensitivity of U87-EGFRvIII in vitro and has a better antitumor effect on ¹⁸⁸Re-U2 in vivo. Therefore, the results revealed the promising potential of the U2 aptamer to be a new type of drug candidate and aptamer-targeted drug delivery system for glioblastoma therapy.

多形性胶质母细胞瘤（GBM）是脑中最常见和最致命的恶性颅内肿瘤，预后和生存率非常差。表皮生长因子受体变体 III (EGFRvIII) 有助于增加致癌性，这种增加的致癌性不是通过结合 EGFR 配体发生的，而是通过组成性激活发生的，从而增强了神经胶质瘤的致瘤性和对靶向治疗的抵抗力。适体是对通过指数富集配体系统进化（SELEX）选择的靶标具有高亲和力和特异性的核酸，通常被开发为疾病相关因子的拮抗剂。在此，我们生成了一种针对 U87-EGFRvIII 细胞的 DNA 适体 U2，并证明 U2 改变了 U87-EGFRvIII 细胞的生长、放射敏感性和胶质母细胞瘤细胞的放射治疗。我们通过流式细胞术和共聚焦显微镜检测U2和U87-EGFRvIII细胞，以探讨U2与U87-EGFRvIII细胞的结合能力。然后，我们发现适体U2抑制U87-EGFRvIII细胞的增殖、迁移、侵袭和下游信号传导。而且，该U2适配体在体外能够增加U87-EGFRvIII的放射敏感性，在体内对^188Re -U2具有更好的抗肿瘤作用。因此，结果揭示了U2适体作为新型候选药物和适体靶向药物递送系统用于胶质母细胞瘤治疗的广阔潜力。