chapter  Chapter 94
24 Pages

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

WithSamuel A. Jensen, Emily S. Day, Caroline H. Ko, Lisa A. Hurley, Janina P. Luciano, Fotini M. Kouri, Timothy J. Merkel, Andrea J. Luthi, Pinal C. Patel, Joshua I. Cutler, Weston L. Daniel, Alexander W. Scott, Matthew W. Rotz, Thomas J. Meade, David A. Giljohann, Chad A. Mirkin, Alexander H. Stegh

Glioblastoma multiforme (GBM) is a neurologically debilitating disease that culminates in death 14 to 16 months after diagnosis. An incomplete understanding of how cataloged genetic aberrations promote therapy resistance, combined with ineffective drug delivery to the central nervous system, has rendered GBM incurable. This chapter preclinically evaluates an RNA interference (RNAi)–based nanomedicine platform, based on spherical nucleic acid (SNA) nanoparticle conjugates, to neutralize oncogene expression in GBM. SNAs consist of gold nanoparticles covalently functionalized with densely packed, highly oriented small interfering RNA duplexes. In the absence of auxiliary transfection strategies or chemical modifications, SNAs efficiently entered primary and transformed glial cells in vitro. In vivo, the SNAs penetrated the blood–brain barrier and blood–tumor barrier to disseminate throughout xenogeneic glioma explants. The chapter evaluates SNA nanoparticle conjugates as an RNAi-based therapy for glioblastoma.