From a therapeutic standpoint, targeting the FOSL1/IKKα/UCHL3 feedback axis yielded significant attenuation of multiple malignant phenotypes of GBM using a novel nanoparticle-based siRNA delivery system (plofsome@<i>siFOSL1</i>), which effectively suppressed <i>FOSL1</i> expression. Here, FOSL1 is linked to glioblastoma.