胶质母细胞瘤（GBM）是一种发病率高、生存率低的中枢神经系统癌症。增强药物对血脑屏障（BBB）的渗透和靶向功效对于改善治疗结果至关重要。在这项研究中，我们开发了一种氧化还原敏感的靶向纳米递送系统（HCA-A2），用于替莫唑胺（TMZ）和β-拉帕酮（β-Lapa）。该系统使用透明质酸（HA）作为亲水基团，花生四烯酸（CA）作为疏水基团，以及angiopep-2（A2）作为靶向基团。控制系统包括非氧化还原敏感（HDA-A2）和非靶向（HCA）版本。在体外，HCA-TMZ-Lapa 胶束在模拟肿瘤微环境中 24 小时内释放了 100% 的有效负载，而正常条件下为 43.97%。通过网格蛋白介导的内吞作用内化的 HCA-A2 胶束比对照表现出更强的细胞毒性以及更好的 BBB 渗透和细胞摄取。体内研究证明 HCA-A2 胶束具有卓越的肿瘤生长抑制作用，表明其治疗 GBM 的潜力。版权所有 © 2024。由 Elsevier Inc. 出版。

Glioblastoma (GBM) is a central nervous system cancer with high incidence and poor survival rates. Enhancing drug penetration of the blood-brain barrier (BBB) and targeting efficacy is crucial for improving treatment outcomes. In this study, we developed a redox-sensitive targeted nano-delivery system (HCA-A2) for temozolomide (TMZ) and β-lapachone (β-Lapa). This system used hyaluronic acid (HA) as the hydrophilic group, arachidonic acid (CA) as the hydrophobic group, and angiopep-2 (A2) as the targeting group. Control systems included non-redox sensitive (HDA-A2) and non-targeting (HCA) versions. In vitro, HCA-TMZ-Lapa micelles released 100 % of their payload in a simulated tumor microenvironment within 24 h, compared to 43.97 % under normal conditions. HCA-A2 micelles, internalized via clathrin-mediated endocytosis, showed stronger cytotoxicity and better BBB penetration and cellular uptake than controls. In vivo studies demonstrated superior tumor growth inhibition with HCA-A2 micelles, indicating their potential for GBM treatment.Copyright © 2024. Published by Elsevier Inc.