Introduction: Glioblastoma (GBM) is a primary brain malignancy with a dismal prognosis and remains incurable at present. In this study, macrophages (MΦ) were developed to carry nanoparticle albumin-bound paclitaxel (nab-PTX) to form nab-PTX/MΦ. The aim of this study is to use a GBM-on-a-chip to evaluate the anti-GBM effects of nab-PTX/MΦ.Methods: In this study, we constructed nab-PTX/MΦ by incubating live MΦ with nab-PTX. We developed a microfluidic chip to co-culture GBM cells and human umbilical vein endothelial cells, mimicking the simplified blood-brain barrier and GBM. Using a syringe pump, we perform sustainable perfusion of nutrient media. To evaluate the anti-GBM effects nab-PTX/MΦ, we treated the GBM-on-a-chip model with nab-PTX/MΦ and investigated GBM cell proliferation, migration, and spheroid formation.Results: At the chosen concentration, nab-PTX did not significantly affect the viability, chemotaxis and migration of MΦ. The uptake of nab-PTX by MΦ occurred within 1 h of incubation and almost reached saturation at 6 h. Additionally, nab-PTX/MΦ exhibited the M1 phenotype, which inhibits tumor progression. Following phagocytosis, MΦ were able to release nab-PTX, and the release of nab-PTX by MΦ had nearly reached its limit at 48 h. Compared with control group and blank MΦ group, individual nab-PTX group and nab-PTX/MΦ group could inhibit tumor proliferation, invasion and spheroid formation. Meanwhile, the anti-GBM effect of nab-PTX/MΦ was more significant than nab-PTX.Discussion: Our findings demonstrate that nab-PTX/MΦ has a significant anti-GBM effect compared to individual nab-PTX or MΦ administration, suggesting MΦ as potential drug delivery vectors for GBM therapy. Furthermore, the developed GBM-on-a-chip model provides a potential ex vivo platform for innovative cell-based therapies and tailored therapeutic strategies for GBM.

中文翻译：

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基于微流控芯片的纳米颗粒白蛋白结合紫杉醇负载巨噬细胞治疗胶质母细胞瘤的评估

简介：胶质母细胞瘤（GBM）是一种原发性脑恶性肿瘤，预后较差，目前仍无法治愈。在这项研究中，巨噬细胞（MΦ）被开发来携带纳米颗粒白蛋白结合的紫杉醇（nab-PTX）形成nab-PTX/MΦ。本研究的目的是使用 GBM-on-a-chip 来评估 nab-PTX/MΦ 的抗 GBM 效果。 方法：在本研究中，我们通过将活 MΦ 与 nab-PTX 一起孵育来构建 nab-PTX/MΦ。 PTX。我们开发了一种微流控芯片来共培养 GBM 细胞和人脐静脉内皮细胞，模仿简化的血脑屏障和 GBM。我们使用注射泵对营养培养基进行可持续灌注。为了评估 nab-PTX/MΦ 的抗 GBM 效果，我们用 nab-PTX/MΦ 处理 GBM 芯片模型，并研究 GBM 细胞增殖、迁移和球体形成。结果：在选定的浓度下，nab -PTX没有显着影响MΦ的活力、趋化性和迁移。 MΦ 对 nab-PTX 的吸收发生在孵育 1 小时内，并在 6 小时时几乎达到饱和。此外，nab-PTX/MΦ 表现出 M1 表型，可抑制肿瘤进展。吞噬作用后，MΦ能够释放nab-PTX，并且MΦ的nab-PTX释放在48小时时几乎达到极限。与对照组和空白MΦ组相比，单独nab-PTX组和nab-PTX/MΦ组能够抑制肿瘤的增殖、侵袭和球体形成。同时，nab-PTX/MΦ 的抗 GBM 作用比 nab-PTX 更显着。讨论：我们的研究结果表明，与单独的 nab-PTX 或 MΦ 给药相比，nab-PTX/MΦ 具有显着的抗 GBM 作用，这表明MΦ 作为 GBM 治疗的潜在药物递送载体。此外，开发的 GBM-on-a-chip 模型提供了潜在的离体基于细胞的创新疗法和 GBM 定制治疗策略的平台。