Combined delivery of temozolomide and the thymidine kinase gene for treatment of glioblastoma

Abstract

Glioblastoma is the most malignant form of brain tumor. In this study, combination therapy with temozolomide (TMZ) and the herpes simplex virus thymidine kinase (HSVtk) gene was evaluated in glioblastoma models. The R7L10 peptide was used as a carrier of TMZ and the HSVtk gene. TMZ was loaded into R7L10 micelles using the oil-in-water emulsion/solvent evaporation method. The TMZ-loaded R7L10 (R7L10-TMZ) micelles formed a complex with the HSVtk gene, pHSVtk. The formation of the R7L10-TMZ/pHSVtk complex was confirmed by gel retardation and heparin competition assays. An in vitro transfection assay demonstrated that the transfection efficiency of R7L10-TMZ was similar to that of R7L10 in C6 glioblastoma cells. R7L10-TMZ had greater anti-tumor effects than TMZ alone in C6 cells in vitro, suggesting that R7L10 is an efficient carrier of TMZ. The in vivo efficacy of the R7L10-TMZ/pHSVtk complex was evaluated in the intracranial glioblastoma model. HSVtk expression in tumors was confirmed by immunohistochemistry. Furthermore, a greater anti-tumor effect was observed in the R7L10-TMZ/pHSVtk group compared with the TMZ or R7L10/pHSVtk single injection group. In conclusion, combined delivery of TMZ and the HSVtk gene using R7L10 peptides may be useful for the treatment of glioblastoma.

β-Elemene Selectively Inhibits the Proliferation of Glioma Stem-Like Cells Through the Downregulation of Notch1

“…Uto et al treated elderly glioblastoma patients with hypofractionated radiotherapy and concurrent TMZ and reported that both overall survival and progression‐free survival were improved []. Choi et al evaluated the effect of combination therapy with the herpes simplex virus thymidine kinase gene and TMZ in glioblastoma models []. An increased antitumor effect was observed in the combination group compared with the single treatment group [].…”

“…Choi et al evaluated the effect of combination therapy with the herpes simplex virus thymidine kinase gene and TMZ in glioblastoma models []. An increased antitumor effect was observed in the combination group compared with the single treatment group []. Silencing of NrF2 (nuclear factor erythroid 2‐related factor 2) and inhibition of glutathione greatly enhanced cell death with TMZ treatment both in vitro and in vivo [, ].…”

Effect of radiotherapy and chemotherapy on levels of serum S100B, IL-6, and IL-17 in patients with malignant glioma

“…Temozolomide, as antitumor drug of alkylating agent, has the main side effects of bone marrow depression and gastrointestinal reactions, but with less toxicity and no accumulation, and the bone marrow suppression can also be reversed, allowing continuous treatment and adding course of treatment. 10 According to the study results, the incidence of grade I–II adverse reactions was 30% in the study group and 32.5% in the control group.…”

Nose-to-Brain Delivery of Cancer-Targeting Paclitaxel-Loaded Nanoparticles Potentiates Antitumor Effects in Malignant Glioblastoma

“…All experiments were performed in compliance with guidelines, using protocols approved by the Institutional Animal Care and Use Committee (IACUC) of the Hanyang University. Intracranial tumor rat models were developed using six-week-old male Sprague–Dawley rats as described . Briefly, the anesthetized rats were placed in a stereotaxic frame, and the skull was gently exposed to spot the bregma.…”

“…Intracranial tumor rat models were developed using six-week-old male Sprague−Dawley rats as described. 38 Briefly, the anesthetized rats were placed in a stereotaxic frame, and the skull was gently exposed to spot the bregma. The monitoring points to the bregma were as follows: anteroposterior, 0 mm; lateral, 2.0 mm; ventral, 4.0 mm.…”