Enhanced Efficacy of Temozolomide Loaded by a Tetrahedral Framework DNA Nanoparticle in the Therapy for Glioblastoma

Glioblastoma (GBM) is one of the deadliest primary brain malignant tumors with a bleak prognosis. Craniotomy surgical resection followed by radiotherapy and chemotherapy was still the standard therapeutic strategy for GBM. As a target alkylating agent, temozolomide (TMZ) was utilized in the therapy of GBM for decades. However, effective treatment for GBM is stymied by rapid acquired resistance and bone marrow suppression. Here, we synthesize a tetrahedral framework nucleic acid (tFNA) nanoparticle that can carry TMZ to enhance the lethality on four GBM cell lines via activating the cell apoptosis and autophagy pathway. Our nanoparticle, namely, tFNA-TMZ, shows a more obvious efficacy in killing TMZ-sensitive cells (A172 and U87) than single-agent TMZ. Besides, tFNA-TMZ was able to attenuate drug resistance in TMZ-resistant cells (T98G and LN-18) via downregulating the expression of O6-methylguanine-DNA-methyltransferase. Furthermore, we modified the tFNA with GS24, a DNA aptamer that can specially bind to transferrin receptor in the cerebral vascular endothelial cell of mouse and enable the tFNA nanoparticle to cross the blood-brain barrier. In summary, our results demonstrated that tFNA-TMZ has a promising role as a nanoscale vehicle to deliver TMZ to enhance the efficacy of GBM.