(17c) ssDNA Nanotubes Targeting Glioblastoma Multiforme

Brain tumors are one of the leading causes of death from neurologic disease. The most malignant type, glioblastoma multiforme (GBM), represents 30% of primary tumors. Patients diagnosed with grade IV GBM have a median survival of 11 months after diagnosis and a 5-year survival rate of less than 5%. Despite recent advances in neurosurgery, chemotherapy, and radiation therapy, there has been little significant change in the long-term survival of patients with malignant astrocytic neoplasms. New therapeutic approaches that will be specific and more effective for the treatment of GBM are urgently needed. In this work we have designed ssDNA nanotubes from the self-assembly of single-stranded DNA (ssDNA)-amphiphiles and used them to target GL261 mouse glioma cells in vitro and in vivo in an orthotopic mouse model of GBM. Our work shows that the ssDNA nanotubes bind and internalize into the GL261 cells with minimal surface binding on control healthy cells. Intrastriatal injections of the ssDNA nanotubes showed preferential retention of the ssDNA nanotubes on the tumor-bearing side of the brain with no accumulation on the healthy side of the brain. The ssDNA nanotubes were also delivered by intravenous injection and their biodistribution was evaluated at 3 and 24h. The ssDNA nanotubes showed higher accumulation at 3h and accumulated in the brain at higher amounts compared to other spherical nanoparticles reported in the literature. This is the first demonstration of ssDNA nanotubes targeting brain cancer cells in vitro and in vivo and results show that our ssDNA nanotubes are promising vehicles for the future delivery of therapeutic nucleic acids to brain tumors.