Importantly, our nanocomplex is able to target CSCs that are considered to be the prime culprits in therapeutic resistance and recurrence of GBM. Attenuation of MALAT1 by RNA interference significantly lowered the growth, motility and stemness of GBM cells. In addition, silencing of MALAT1 clearly improved the sensitivity of GBM cells to chemotherapeutic agents including the current first-line therapy of GBM [temozolomide (TMZ)]. In animal models of GBM, tumor involution with a modest but statistically significant survival benefit was achieved with concurrent treatment of TMZ and nanocomplex-mediated silencing of MALAT1.Expressions of both OCT4 and NANOG, transcription factors known to maintain pluripotency and self-renewal of embryonic stem cells, were significantly reduced (34.2% and 20.2%, respectively) after scL-siMAL treatment.