Most importantly, the antiangiogenic efficacy of ATMO‐21 toward orthotopic human GBM was first investigated carefully, indicating that B1L@SpAcDex‐ATMO‐21 NPs could significantly inhibit the expression of tumor blood vessel‐related genes (HIF1α and VEGF) by upregulating PTEN expression. Here, PTEN is linked to glioblastoma.