Inhibition of Neuroblastoma Tumor Growth by Targeted Delivery of MicroRNA-34a Using Anti-Disialoganglioside GD.sub.2 Coated Nanoparticles

• Published in: PloS one 2012-05, Vol.7 (5), p.e38129
• Main Authors: Tivnan, Amanda, Orr, Wayne Shannon, Gubala, Vladimir, Nooney, Robert, Williams, David E, McDonagh, Colette, Prenter, Suzanne, Harvey, Harry, Domingo-Fernández, Raquel, Bray, Isabella M, Piskareva, Olga, Ng, Catherine Y, Lode, Holger N, Davidoff, Andrew M, Stallings, Raymond L
• Format: Article
• Language: English
• Subjects: Antibodies; Antigens; Apoptosis; Gangliosides; Growth; Health aspects; MicroRNA; Neuroblastoma; Recurrence (Disease); Silicon dioxide
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0038129

Neuroblastoma is one of the most challenging malignancies of childhood, being associated with the highest death rate in paediatric oncology, underlining the need for novel therapeutic approaches. Typically, patients with high risk disease undergo an initial remission in response to treatment, followed by disease recurrence that has become refractory to further treatment. Here, we demonstrate the first silica nanoparticle-based targeted delivery of a tumor suppressive, pro-apoptotic microRNA, miR-34a, to neuroblastoma tumors in a murine orthotopic xenograft model. These tumors express high levels of the cell surface antigen disialoganglioside GD2 (GD.sub.2 ), providing a target for tumor-specific delivery. These novel findings highlight the potential of anti-GD.sub.2 -nanoparticle-mediated targeted delivery of miR-34a for both the treatment of GD.sub.2 -expressing tumors, and as a basic discovery tool for elucidating biological effects of novel miRNAs on tumor growth.