Targeting transferrin receptor delivery of temozolomide for a potential glioma stem cell-mediated therapy

Abstract

Glioma stem cells, which are sub-populations of tumor cells, are responsible for resistant responses to radiotherapy and chemotherapy after surgery. Targeting resistant glioma stem cell sub-populations might present a novel means to prevent tumor recurrence. Due to the high expression of transferrin receptors at the surface of brain capillary endothelial and tumor cells, especially glioma stem cells, targeting the transferrin receptor system provides an avenue for the entry of drug molecules into the brain. Nanoparticles that target glioma stem cell sub-populations, conjugate transferrin and encapsulate temozolomide, were developed as a potential therapeutic strategy to evaluate their effectiveness at damaging tumor cells. Nanoparticles were highly effective at penetrating the blood-brain barrier and delivering a high therapeutic dose of temozolomide. This effective means of delivery provoked enhanced cytotoxicity against glioma cells, and especially against glioma stem cells. The targeting transferrin receptor nanoparticles display an inherent capacity for a highly therapeutic approach in targeting glioma stem cells and non-stem cells tumors. In addition, transferrin nanoparticles encapsulating temozolomide have the potential of a promising anti-tumor strategy against glioma of the O6-methylguanine-DNA-methyltransferase gene promoter methylation.