Glioblastoma multiforme (GBM) is one of the most daunting issues to modern therapeutics, with a higher mortality rate post-diagnosis. Temozolomide (TMZ) is the only available treatment; however, the frequent resistance leaves the oncologists at a dead end. Therefore, new approaches to circumvent the GBM are highly desired. We have employed TiO2 nanosticks loaded with TMZ as nanomedicine for TMZ-resistant GBM resection in this contribution. The ultrasonication triple-action effect could greatly facilitate tumor ablation by enhancing the TiO2 nanosticks traversing across BBB, releasing the TMZ payload from TiO2 nanosticks and reactive oxygen species (ROS) generation from TiO2 nanosticks within the GBM milieu. The tumor ablation was confirmed by MTT and Annexin(v)-PI assays, apoptotic proteins expression via western blot and ROS level detection in vitro, whereas tumor volume, weight, survival rate, and relative photon flux in the xenograft and orthoptic TMZ-resistant GBM murine models as in vivo. We found this nanomedicine-based ultrasound modality highly efficient in GBM treatment and is of future clinical application value due to the employment of already FDA-approved techniques and nanomedicine.

中文翻译：

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载有替莫唑胺的超声活化纳米TiO ₂为切除化疗耐药的多形性胶质母细胞瘤铺平了道路

多形性胶质母细胞瘤 (GBM) 是现代疗法中最令人生畏的问题之一，诊断后死亡率更高。替莫唑胺 (TMZ) 是唯一可用的治疗方法；然而，频繁的抵抗让肿瘤学家陷入了死胡同。因此，非常需要绕过 GBM 的新方法。在这个贡献中，我们使用了载有 TMZ 的 TiO2 纳米棒作为纳米药物用于 TMZ 抗性 GBM 切除。超声处理的三重作用可以通过增强 TiO2 纳米棒穿过 BBB、从 TiO2 纳米棒释放 TMZ 有效载荷和从 GBM 环境中的 TiO2 纳米棒产生活性氧 (ROS) 来极大地促进肿瘤消融。通过 MTT 和 Annexin(v)-PI 检测证实肿瘤消融，通过体外蛋白质印迹和 ROS 水平检测的凋亡蛋白表达，而异种移植物和正视 TMZ 抗性 GBM 小鼠模型中的肿瘤体积、重量、存活率和相对光子通量与体内相同。我们发现这种基于纳米医学的超声方式在 GBM 治疗中非常有效，并且由于采用了 FDA 批准的技术和纳米医学，因此具有未来的临床应用价值。