In addition, because both endothelial cells in the blood-brain barrier (BBB) and glioma cells show high expression of receptor-related protein 1 (LRP-1), which is high binding affinity to its ligand Angiopep-237, conjugated Angiopep-2 is then able to efficiently drive the developed Ang-SS-Cas9/sgIGFBP5 nanocapsules across the BBB and subsequently actively target GSCs in the brain, towards effective IGFBP5 gene editing via reductive-responsive Cas9/sgIGFBP5 release. Here, LRP1 is linked to glioma.