Glioblastoma (GBM) belongs to the deadliest primary malignancies with high mortality rate and poor prognosis. Over the past decades, less progress has been made to treat GBM, owing largely to the lack of effective chemotherapeutics and poor drug accumulation in the glioma tissue. In order to address this issue, we present an efficient biomimetic nanocomposite (Cu_2−xSe-CB@MEM, CCM), consisting of Cu_2−xSe nanoparticle core modified by cinobufotalin (CB), a toad venom extract, which is camouflaged with glioma cell Ln229 membrane. It is demonstrated that CB can decrease the protein activity of inosine monophosphate dehydrogenase 1 (IMPDH1), a key target correlated with prognosis, through intermolecular hydrogen bonding with amino acid residues ARG-105 and ASP-77. The glioma cell membrane-camouflage endows the CCM with blood-brain barrier penetration and homology tumor-targeted ability. The optimized cinobufotalin based chemotherapy combining with the near-infrared-II (NIR-II) irradiation shows outstanding inhibition effect to glioma cells, by blocking cell cycle and inducing apoptosis. In vivo mice bearing orthotopic Ln229 GBM treated with CCM+NIR-II (CCM+L) have significantly suppressed tumor growth and extended survival, without side effect. The glioma cell membrane camouflaged nanocomposite of Cu_2−xSe and cinobufotalin with its significant anti-glioma property and well biosafety will provide novel alternatives for clinical treatment of GBM.

胶质母细胞瘤（GBM）属于最致命的原发性恶性肿瘤，死亡率高，预后差。在过去的几十年里，治疗 GBM 的进展较少，这主要是由于缺乏有效的化疗药物和胶质瘤组织中的药物蓄积不良。为了解决这个问题，我们提出了一种高效的仿生纳米复合材料（Cu _2−x Se-CB@MEM，CCM），由 Cu _2−x华蟾素 (CB) 修饰的硒纳米颗粒核，华蟾素是一种蟾蜍毒液提取物，用神经胶质瘤细胞 Ln229 膜伪装。结果表明，CB 可以通过与氨基酸残基 ARG-105 和 ASP-77 的分子间氢键结合，降低肌苷一磷酸脱氢酶 1 (IMPDH1) 的蛋白质活性，IMPDH1 是与预后相关的关键靶点。胶质瘤细胞膜伪装赋予CCM穿透血脑屏障和同源肿瘤靶向能力。优化的基于华蟾素的化疗结合近红外-II (NIR-II) 照射通过阻断细胞周期和诱导细胞凋亡对神经胶质瘤细胞显示出显着的抑制作用。体内用 CCM+NIR-II (CCM+L) 处理的携带原位 Ln229 GBM 的小鼠显着抑制了肿瘤生长并延长了生存期，并且没有副作用。神经胶质瘤细胞膜伪装的Cu _2-x Se和华蟾素纳米复合材料具有显着的抗神经胶质瘤特性和良好的生物安全性，将为临床治疗GBM提供新的替代方案。