Abstract
BackgroundGlioblastoma 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.ResultsThe 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.ConclusionWe 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.
Highlights
Glioblastoma multiforme (GBM) is one of the most daunting issues to modern therapeutics, with a higher mortality rate post-diagnosis
The suboptimal concentration of TMZ at the tumor site, frequent development of chemoresistance, and the Rehman et al Cancer Nano (2021) 12:17 blood–brain barrier (BBB) selective amenability are some of the major bottlenecks in complete resection of GBM (Haar et al 2012; Casals et al 2017; Bahadur et al 2019)
The TEM revealed the porous nature of the TiO2 nanosticks that played an essential role in the drug loading, as shown in Fig. 1b inset
Summary
Glioblastoma multiforme (GBM) is one of the most daunting issues to modern therapeutics, with a higher mortality rate post-diagnosis. The suboptimal concentration of TMZ at the tumor site, frequent development of chemoresistance, and the Rehman et al Cancer Nano (2021) 12:17 blood–brain barrier (BBB) selective amenability are some of the major bottlenecks in complete resection of GBM (Haar et al 2012; Casals et al 2017; Bahadur et al 2019). The BBB is only amenable to small molecules (i.e., < 400 Da size and < 9 hydrogen bonding, CO2, O2, alcohol, and glucose, etc.) (Abbott et al 2006) It constrains 98% of all other biochemicals and drugs that may be efficient therapeutic agents in other parts of the body (Mitragotri 2013). Liu et al (2014) employed focused ultrasound to reversibly break the BBB and enhance the TMZ localization in GBM from 6.98 to 19 ng/mg. Likewise, during the phase I clinical trial, Lipsman et al (2018) employed focused ultrasound to open BBB in Alzheimer’s disease (AD) patients, lowering the β amyloid plaques and tau protein aggregates resulting in AD’s amelioration
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