Glioblastoma is the most common malignant brain tumor. Efficient delivery of drugs targeting glioblastomas remains a challenge. Ephrin type-A receptor 3 (EPHA3) tyrosine kinase antibody-modified polylactide-co-glycolide (PLGA) nanoparticles (NPs) were developed to target glioblastoma via nose-to-brain delivery. Anti-EPHA3-modified, TBE-loaded NPs were prepared using an emulsion-solvent evaporation method, showed a sustained in vitro release profile up to 48 h and a mean particle size of 145.9 ± 8.7 nm. The cellular uptake of anti-EPHA3-modified NPs by C6 cells was significantly enhanced compared to that of nontargeting NPs (p < .01). In vivo imaging and distribution studies on the glioma-bearing rats showed that anti-EPHA3-modified NPs exhibited high fluorescence intensity in the brain and effectively accumulated to glioma tissues, indicating the targeting effect of anti-EPHA3. Glioma-bearing rats treated with anti-EPHA3-modified NPs resulted in significantly higher tumor cell apoptosis (p < .01) than that observed with other formulations and prolonged the median survival time of glioma-bearing rats to 26 days, which was 1.37-fold longer than that of PLGA NPs. The above results indicated that anti-EPHA3-modified NPs may potentially serve as a nose-to-brain drug carrier for the treatment of glioblastoma.

中文翻译：

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经抗EPHA3功能化的替莫唑胺负载的PLGA纳米颗粒从鼻腔到脑部的递送，可用于靶向胶质母细胞瘤。

胶质母细胞瘤是最常见的恶性脑肿瘤。有效递送靶向胶质母细胞瘤的药物仍然是一个挑战。Ephrin A型受体3（EPHA3）酪氨酸激酶抗体修饰的聚乳酸-乙交酯（PLGA）纳米颗粒（NPs）被开发为通过鼻-脑递送靶向胶质母细胞瘤。使用乳液-溶剂蒸发法制备了抗EPHA3修饰的，加载了TBE的NP，显示出持续的体外释放曲线长达48小时，平均粒径为145.9±8.7 nm。与非靶向NP相比，C6细胞对抗EPHA3修饰的NP的细胞摄取显着增强（p <0.01）。对具有神经胶质瘤的大鼠的体内成像和分布研究表明，抗EPHA3修饰的NP在大脑中显示出高荧光强度，并有效地积累到神经胶质瘤组织中，指示抗EPHA3的靶向作用。用抗EPHA3修饰的NPs治疗的神经胶质瘤大鼠比其他制剂观察到的肿瘤细胞凋亡显着更高（p <.01），并且将神经胶质瘤大鼠的中位生存时间延长至26天，即1.37-比PLGA NP长一倍。上述结果表明，抗EPHA3修饰的NP可能潜在地用作治疗胶质母细胞瘤的从鼻到脑的药物载体。