恶性胶质瘤是一种起源于胶质细胞的原发性脑肿瘤。其中，多形性胶质母细胞瘤（GBM）是成人中最常见和最具侵袭性的脑肿瘤，被世界卫生组织分类为第四级。GBM的标准治疗，即Stupp协议，包括手术切除并随后口服替莫唑胺（TMZ）化疗。这种治疗选项仅为患者提供了中位生存预后16-18个月，主要是由于肿瘤复发。因此，迫切需要对这种疾病进行增强治疗。在这里，我们展示了一种新的复合材料的开发、表征以及GBM术后局部治疗的体外和体内评估。我们开发了响应性纳米颗粒，其中载有紫杉醇（PTX），并且表现出对3D球体和细胞的穿透和内部化。这些纳米颗粒在GBM的2D（U-87细胞）和3D（U-87球体）模型中被发现具有细胞毒性。将这些纳米颗粒结合到凝胶中有助于使它们在时间上持续释放。此外，这种含有PTX载药响应性纳米颗粒和自由TMZ的凝胶的配方能够延缓手术切除后的肿瘤复发。因此，我们的配方代表了一种有前途的方法，利用含有纳米颗粒的注射性水凝胶开发组合的局部治疗GBM。©2023作者。

Malignant gliomas are a type of primary brain tumour that originates in glial cells. Among them, glioblastoma multiforme (GBM) is the most common and the most aggressive brain tumour in adults, classified as grade IV by the World Health Organization. The standard care for GBM, known as the Stupp protocol includes surgical resection followed by oral chemotherapy with temozolomide (TMZ). This treatment option provides a median survival prognosis of only 16-18 months to patients mainly due to tumour recurrence. Therefore, enhanced treatment options are urgently needed for this disease. Here we show the development, characterization, and in vitro and in vivo evaluation of a new composite material for local therapy of GBM post-surgery. We developed responsive nanoparticles that were loaded with paclitaxel (PTX), and that showed penetration in 3D spheroids and cell internalization. These nanoparticles were found to be cytotoxic in 2D (U-87 cells) and 3D (U-87 spheroids) models of GBM. The incorporation of these nanoparticles into a hydrogel facilitates their sustained release in time. Moreover, the formulation of this hydrogel containing PTX-loaded responsive nanoparticles and free TMZ was able to delay tumour recurrence in vivo after resection surgery. Therefore, our formulation represents a promising approach to develop combined local therapies against GBM using injectable hydrogels containing nanoparticles.© 2023. The Author(s).