Ultrasound-activated nano-TiO2 loaded with temozolomide paves the way for resection of chemoresistant glioblastoma multiforme

Abstract

Abstract Background 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. Results 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. Conclusion 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.

Keywords

• Temozolomide resistance
• Glioblastoma multiforme
• Ultrasound
• TiO2 nanosticks
• Blood–brain barrier