Inhibition of retinoblastoma tumor progression using catalytic antioxidant naoparticles

Abstract

Purpose: Retinoblastoma is a malignant tumor of retinal origin arising during development. Tumorigenesis and progression of retinoblastoma is associated with a rise in reactive oxygen species and dependent downstream signaling cascades leading to tumor growth and vascularization. Catalytic antioxidant cerium oxide nanoparticles (nanoceria) function as regenerative superoxide dismutase (SOD1) and catalase mimetics. Our published data indicate that nanoceria are potent down regulators of vascular endothelial growth factor (VEGF) and neovascularization and our current data support the therapeutic use of nanoceria in a heritable model of retinoblastoma.

Methods: Fundoscopic and magnetic resonance images were obtained from (P53TKO mice, Chx-10-cre; Rb lox/- ; p53 lox/-; p107 -/-) following tumorigenesis. A single dose of nanoceria (172 ng/eye) was delivered into the vitreous at baseline. Follow-up imaging was performed at 1 and 3 weeks post-injection. Tumor size, vascularity, and perfusion were monitored using funduscopy, MRI and fluorescein angiography. Western blot, PCR-Array, and immunocytochemistry were used to evaluate changes in ROS-mediated gene and protein expression.

Results: Histology and fundoscopic imaging demonstrate a significant decrease in tumor burden and invasion of the anterior chamber following treatment with nanoceria.

Conclusions: Nanoceria are novel inhibitors of tumor growth in vivo and may represent a novel vision-sparing therapeutic in the multifaceted approach to the treatment of ocular malignancy.

Keywords: 703 retinoblastoma • 748 vascular endothelial growth factor • 608 nanomedicine