Abstract
Glioblastoma (GBM) is the commonest form of primary brain tumor in the central nervous system, with median survival below 15 months and only a 25% two-year survival rate for patients. One of the major clinical challenges in treating GBM is the presence of the blood–brain barrier (BBB), which greatly limits the availability of therapeutic drugs to the tumor. Ultrasound-mediated BBB opening provides a promising approach to help deliver drugs to brain tumors. The use of temozolomide (TMZ) in the clinical treatment of GBM has been shown to be able to increase survival in patients with GBM, but this improvement is still trivial. In this study, we developed a liposomal temozolomide formulation (TMZ-lipo) and locally delivered these nanoparticles into GBM through ultrasound-mediated BBB opening technology, significantly suppressing tumor growth and prolonging tumor-bearing animal survival. No significant side effects were observed in comparison with control rats. Our study provides a novel strategy to improve the efficacy of TMZ against GBM.
Highlights
Glioblastoma (GBM) is the most common form of primary brain tumor in the central nervous system, with a median survival below 15 months and only a 25% two-year survival rate [1,2]
The blood–brain barrier (BBB) is still a major limitation reducing the efficacy of anti-cancer drugs in the treatment of GBM
We examined whether the TMZ-lipo could induce glioma cell apoptosis by using transferase-mediated dUTP nick-end labeling (TUNEL) assays and immunohistochemical staining of caspase-3
Summary
Glioblastoma (GBM) is the most common form of primary brain tumor in the central nervous system, with a median survival below 15 months and only a 25% two-year survival rate [1,2]. Survival advantages have been demonstrated with postoperative radiation therapy at doses of 5000–6000 cGy, but this treatment has been shown to increase toxicity without additional survival benefit beyond 6000 cGy. In the past decades, pharmacological progresses have been made, leading to the development of molecular targeted therapies or precision medicine approaches [7]. Various novel drug formulations, delivery systems, and tumor-targeting strategies to inhibit the tumor progression or metastasis of GBM have been being widely studied [8,9,10]. The blood–brain barrier (BBB) is still a major limitation reducing the efficacy of anti-cancer drugs in the treatment of GBM patients [11,12]
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