Dual-triggered biomimetic vehicles enable treatment of glioblastoma through a cancer stem cell therapeutic strategy

Glioma stem cells (GSCs) and their complex microenvironment play a crucial role in the high invasion of cancer and therapeutic resistance and are considered to be the most likely cause of cancer relapse. We constructed a biomimetic vehicle (LDL-SAL-Ang) based on a low density lipoprotein triggered by Angiopep-2 peptide and ApoB protein, to improve the transport of an anti-GSC therapeutic agent into the brain. The LDL-SAL-Ang showed significant inhabitation for GSC microsphere formation and induced the highest apoptotic rate in two types of GSCs. LDL-SAL-Ang reduced the number of GSC-derived endothelial tubules at a lower drug concentration and inhibited endothelial cell migration and angiogenesis. The pharmacokinetic analysis showed that the brain tissue uptake rate (% ID g −1 ) for LDL-SAL-Ang was significantly enhanced at 0.45. For anti-glioblastoma activity in vivo , the median survival time of LDL-SAL-Ang plus temozolomide group was 47 days, which were significantly increased compared with the control or temozolomide only groups. The endogenous biomimetic nanomedicine that we designed provides a potential approach to improve treatments for intracranial tumors and reduced neurotoxicity of nanomedicine. Biomimetic nanocarrier structure and schematic illustration of the proposed strategy of promoting the treatment of glioma for cancer stem cell therapy in combination with chemotherapeutics.