Glioblastoma multiforme (GBM) is the most aggressive form of brain tumour and treatment is very challenging. Despite the recent advances in drug delivery systems, various approaches that allow sufficient deposition of anti-cancer drugs within the brain remain unsuccessful due to limited drug delivery throughout the brain. In this study, we utilised an intranasal (IN) approach to allow delivery of anti-cancer drug, encapsulated in PLGA nanoparticles (NPs). PLGA NPs were modified with the RGD ligand to enable A_vβ₃ expressing tumour-specific delivery. IN delivery of RGD-conjugated-doxorubicin (DOX)-loaded-PLGA-nanoparticles (RGD-DOX-NP) showed cancer-specific delivery of NP and inhibition of brain tumour growth compared to the free-DOX or non-modified DOX-NP in the C6-implanted GBM model. Further, IN treatment with RGD-DOX-NP induces apoptosis in the tumour region without affecting normal brain cells. Our study provides therapeutic evidence to treat GBM using a non-invasive IN approach, which may further be translated to other brain-associated diseases.

多形性胶质母细胞瘤 (GBM) 是最具侵袭性的脑肿瘤，治疗非常具有挑战性。尽管药物输送系统最近取得了进展，但由于整个大脑的药物输送有限，各种允许抗癌药物在大脑内充分沉积的方法仍然不成功。在这项研究中，我们利用鼻内 (IN) 方法允许递送封装在 PLGA 纳米颗粒 (NPs) 中的抗癌药物。PLGA NPs 用 RGD 配体修饰，以启用 A _v β ₃表达肿瘤特异性递送。与游离 DOX 或未修饰的 DOX-NP 相比，在递送 RGD 偶联多柔比星 (DOX) 负载 PLGA 纳米颗粒 (RGD-DOX-NP) 时显示出 NP 的癌症特异性递送和脑肿瘤生长抑制在 C6 植入 GBM 模型中。此外，用 RGD-DOX-NP 进行 IN 治疗可在肿瘤区域诱导细胞凋亡，而不会影响正常脑细胞。我们的研究提供了使用非侵入性 IN 方法治疗 GBM 的治疗证据，该方法可能进一步转化为其他脑相关疾病。