RNA nanoparticle as a vector for targeted siRNA delivery into glioblastoma mouse model

// Tae Jin Lee 1 , Farzin Haque 2 , Dan Shu 2 , Ji Young Yoo 3 , Hui Li 2 , Robert A. Yokel 2 , Craig Horbinski 4 , Tae Hyong Kim 3,5 , Sung-Hak Kim 3 , Chang-Hyuk Kwon 3,6 , Ichiro Nakano 3 , Balveen Kaur 3 , Peixuan Guo 2 , Carlo M. Croce 1 1 Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA 2 Department of Pharmaceutical Sciences, Nanobiotechnology Center, Markey Cancer Center, College of Pharmacy, University of Kentucky, Lexington, KY, USA 3 Department of Neurological Surgery, Dardinger Laboratory for Neuro-oncology and Neurosciences, The Ohio State University Medical Center, Columbus, OH, USA 4 Division of Neuropathology, Department of Pathology, University of Kentucky, Lexington, KY, USA 5 ProteomeTech Inc., Seoul, Korea 6 Neurosciences Research Program, Aurora Health Care Inc., Milwaukee, WI, USA Correspondence to: Carlo M. Croce, email: // Peixuan Guo, email: // Keywords : pRNA, nanoparticle, three-way junction, glioblastoma, siRNA Received : February 14, 2015 Accepted : March 01, 2015 Published : March 23, 2015 Abstract Systemic siRNA administration to target and treat glioblastoma, one of the most deadly cancers, requires robust and efficient delivery platform without immunogenicity. Here we report newly emerged multivalent naked RNA nanoparticle (RNP) based on pRNA 3-way-junction (3WJ) from bacteriophage phi29 to target glioblastoma cells with folate (FA) ligand and deliver siRNA for gene silencing. Systemically injected FA-pRNA-3WJ RNPs successfully targeted and delivered siRNA into brain tumor cells in mice, and efficiently reduced luciferase reporter gene expression (4-fold lower than control). The FA-pRNA-3WJ RNP also can target human patient-derived glioblastoma stem cells, thought to be responsible for tumor initiation and deadly recurrence, without accumulation in adjacent normal brain cells, nor other major internal organs. This study provides possible application of pRNA-3WJ RNP for specific delivery of therapeutics such as siRNA, microRNA and/or chemotherapeutic drugs into glioblastoma cells without inflicting collateral damage to healthy tissues.