A tumor-targeting p53 nanodelivery system limits chemoresistance to temozolomide prolonging survival in a mouse model of glioblastoma multiforme

Both inherent and acquired resistance to current standard-of-care chemotherapeutic agent temozolomide (TMZ) contributes to the poor prognosis in GBM patients. SGT-53 is a tumor-targeted nanocomplex delivering the tumor suppressor gene wtp53 into tumor cells by binding to the transferrin receptor (TfR). Here, we demonstrate that systemic administration of SGT-53, which crosses the blood-brain barrier via the TfR on brain endothelium, significantly enhances the anti-tumor efficacy of TMZ in vivo and limits the development of chemoresistance in GBM tumors by directly modulating MGMT levels. These results suggest that combining SGT-53 with TMZ could be a more effective therapy for GBM.291