Department of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China.
Nanomedicine. 2024 Oct;61:102772. doi: 10.1016/j.nano.2024.102772. Epub 2024 Jul 2.
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.
胶质母细胞瘤（GBM）是一种中枢神经系统癌症，发病率高，生存率低。增强血脑屏障（BBB）的药物渗透和靶向疗效对于改善治疗结果至关重要。在这项研究中，我们开发了一种针对替莫唑胺（TMZ）和β-拉帕醌（β-Lapa）的氧化还原敏感靶向纳米递药系统（HCA-A2）。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，以及血管生成肽-2（A2）作为靶向基团。对照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%的有效载荷，而在正常条件下释放了 43.97%。通过网格蛋白介导的内吞作用内化的 HCA-A2 胶束表现出更强的细胞毒性和更好的 BBB 穿透和细胞摄取能力，优于对照。体内研究表明，HCA-A2 胶束具有优越的肿瘤生长抑制作用，表明其在 GBM 治疗中的潜力。
