RBCm vesicles from RBCs were functionalized by incorporating ApoE peptide as a targeting ligand following our previous protocol to obtain ApoE­RBCm.[18] The ApoE peptide can specifically bind to the low‐density lipoprotein receptor family (LDLRs) highly expressed on both brain endothelial and tumor cells, leading to the “two birds, one stone” targeting strategy where ApoE will drive ABNM@TMZ/OTX to pass the BBB firstly and then target the tumor cells in brain. Here, APOE is linked to neoplasm.