NT-16 * NANOPARTICLE-MEDIATED DELIVERY OF ANTI-Ape1 siRNA SENSITIZES PEDIATRIC BRAIN TUMOR CELLS TO RADIATION THERAPY BY INHIBITING DNA REPAIR

Pediatric brain tumors are the leading cause of death in children, and survival is frequently accompanied by one or more radiation-induced adverse developmental and psychosocial sequelae. Radiotherapy (RT) is an integral component of the treatment for medulloblastoma (MB) and the only effective adjuvant therapy for ependymoma (EP). Therefore, there is an urgent need to develop strategies to enhance the tumoricidal action of RT while sparing adjacent normal tissue. The multifunctional DNA repair protein Ape1/Ref-1 has been implicated in conferring radiation resistance in pediatric brain tumors. However, inhibiting Ape1 activity in the clinic has been hindered by the lack of safe and effective drugs and siRNA delivery vehicles. We have previously developed a nanoparticle that can deliver siRNA specifically to brain tumors for efficient knockdown of GFP. Here, we aimed to deliver siRNA against Ape1 to improve tumor cell kill after RT. Nanoparticles were loaded with siApe1, or siGFP as a control, and used to treat UW228 (MB) and Res196 (EP) cells. Ape1 expression levels were measured using PCR and Western blot, and the abasic endonuclease activity of Ape1 was determined using an Ape activity assay. Cells were then treated with 137Cs--rays and cell survival monitored using clonogenic assays. DNA repair in cells was assessed though quantification of abasic sites, and resulting double-strand breaks were imaged by H2AX foci immunostaining. We found that nanoparticle-mediated siApe1 d...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: NOVEL THERAPEUTICS (CLINICAL AND/OR LABORATORY RESEARCH) Source Type: research