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Targeting retinoblastoma: therapeutic inhibition using catalytic antioxidant cerium oxide nanoparticles
Author(s) -
Klump Kathryn Ellen,
Cai Xue,
Towner Rheal,
Seal Sudipta,
Dyer Michael,
McGinnis James
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1088.16
Subject(s) - retinoblastoma , cancer research , chemistry , carcinogenesis , angiogenesis , reactive oxygen species , neovascularization , downregulation and upregulation , superoxide dismutase , western blot , pathology , microbiology and biotechnology , antioxidant , medicine , biology , biochemistry , gene
Retinoblastoma is a malignant ocular tumor arising within the neural tissue lining the back of the eye during development. An excessive rise in reactive oxygen species (ROS) is associated with signaling cascades and mutagenic events during tumor initiation and angiogenesis in retinoblastoma. Cerium oxide nanoparticles (nanoceria) mimic the action of super oxide dismutase (SOD1) and catalase to destroy ROS. Our published data indicate that nanoceria are capable of reducing pathologic neovascularization in the mouse retina. We hypothesize that in vivo treatment with catalytic antioxidant nanoparticles will result in downregulation of VEGF, inihibition of angiogenesis, and decreased tumor growth in a mouse model of heritable retinoblastoma (P53TKO mice, Chx10‐cre; Rb Lox/−; p53 Lox/−; P107−/−). Mice in these experiments received a single intravitreal injection of nanoceria (172 ng/eye) at the onset of tumorigenesis. Tumor size and vascularity were monitored using fundoscopy, magnetic resonance imaging (MRI), and angiography. Western blot, RT‐PCR array and immunohistochemistry were used to evaluate changes in tumor associated gene and protein expression. Nanoceria resulted in a greater than 50% reduction in tumor burden 3 weeks post‐injection. These data indicate that nanoceria are potent inhibitors of tumor growth and may represent a novel therapeutic approach to targeting ocular malignancy.