Rigosertib formulated in ApoE-targeted chimaeric polymersomes has emerged as a novel, highly specific, efficacious, and nontoxic treatment for glioblastoma.
Here, we report that apolipoprotein E peptide [ApoE, (LRKLRKRLL)<sub>2</sub>C] specifically binds to low-density lipoprotein receptor members (LDLRs) and mediates superb BBB crossing and highly efficient glioblastoma (GBM)-targeted protein therapy in vivo.
Autophagic gene expression was assessed in brains of controls and Alzheimer's disease (AD) patients parsed by APOE genotype and in a glioblastoma cell line expressing either apoE3 or apoE4.
Apolipoprotein E3 (apoE3) is a high density lipoprotein apolipoprotein that chaperones the transcytosis of nanoparticles across the BBB, and displays high-affinity binding with the low density lipoprotein receptor (LDLR), a cell-surface receptor overexpressed by glioblastoma cells.
Apolipoprotein E3-reconstituted high-density lipoprotein is used to encapsulate the siRNA-loaded calcium phosphate core and facilitate it to penetrate the blood-brain barrier, thus targeting the glioblastoma cells in a macropinocytosis-dependent manner.
The ability of apolipoprotein E3 (apoE3) to act as a high-affinity ligand for the low-density lipoprotein receptor (LDLr) was exploited to gain entry of HDL with AuNPs into glioblastoma cells.
ApoE4-induced death occurred with typical features for apoptosis in time- and dose-dependent manners, and was observed in SH-SY5Y neuroblastomas, but not in glioblastomas or non-neuronal Chinese hamster ovary cells.