Spherical Nucleic Acid Nanoparticle Conjugates as an RNAi-Based Therapy for Glioblastoma*

Glioblastoma multiforme is a neurologically debilitating disease that culminates in death 14 to 16 months after diagnosis. Glioblastoma multiforme is the most prevalent and lethal form of malignant brain tumors and considered to be one of the deadliest human cancers. Additional challenges in GBM drug development include ineffective systems for drug delivery to intracerebral tumor elements and the lack of imaging methodologies to quantify intratumoral drug concentrations. RNA interference–based biotherapeutic gene silencing has emerged as a promising approach to target multiple “undruggable” oncogenes implicated in growth, apoptosis, migration, and invasion. Bcl2L12 is a potent caspase and p53 inhibitor that is overexpressed in the vast majority of human primary GBM specimens, yet is at low or undetectable levels in cells of glial origin, in normal brain surrounding tumor tissue, and in low-grade astrocytoma.