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

// Ting Sun 1, * , Haibin Wu 1, * , Yanyan Li 1 , Yulun Huang 1 , Lin Yao 1 , Xionghui Chen 2 , Xiaoxiao Han 1 , Youxin Zhou 1 and Ziwei Du 1 1 Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China 2 Emergency Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China * These authors have contributed equally to the work Correspondence to: Youxin Zhou, email: brain_lab@suda.edu.cn Keywords: targeting delivery, transferrin receptor, glioma stem cells Received: March 15, 2017     Accepted: June 20, 2017     Published: August 10, 2017 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.