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Knight LC, Romano JE, Krynska B, et al. Binding and Internalization of Iron Oxide Nanoparticles Targeted to Nuclear Oncoprotein. J Mol Biomark Diagn. 2010;1(1)doi: 10.4172/2155-9929.1000102.
Knight, L. C., Romano, J. E., Krynska, B., Faro, S., Mohamed, F. B., & Gordon, J. (2010). Binding and Internalization of Iron Oxide Nanoparticles Targeted to Nuclear Oncoprotein. Journal of molecular biomarkers & diagnosis, 1(1), . https://doi.org/10.4172/2155-9929.1000102
Knight, Linda C, et al. "Binding and Internalization of Iron Oxide Nanoparticles Targeted to Nuclear Oncoprotein." Journal of molecular biomarkers & diagnosis vol. 1,1 (2010). doi: https://doi.org/10.4172/2155-9929.1000102
Knight LC, Romano JE, Krynska B, Faro S, Mohamed FB, Gordon J. Binding and Internalization of Iron Oxide Nanoparticles Targeted to Nuclear Oncoprotein. J Mol Biomark Diagn. 2010;1(1). doi: 10.4172/2155-9929.1000102. PMID: 23487404; PMCID: PMC3593723.
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J Mol Biomark Diagn. 2010;1(1). doi: 10.4172/2155-9929.1000102.

Binding and Internalization of Iron Oxide Nanoparticles Targeted to Nuclear Oncoprotein.

Journal of molecular biomarkers & diagnosis

Linda C Knight, Jan E Romano, Barbara Krynska, Scott Faro, Feroze B Mohamed, Jennifer Gordon

Affiliations

  1. Radiology Department, Temple University School of Medicine, Broad and Ontario Streets, Philadelphia, PA 19140.

PMID: 23487404 PMCID: PMC3593723 DOI: 10.4172/2155-9929.1000102

Abstract

A targeted nanoconjugate is being developed for non-invasive detection of gene expression in cells expressing the JC virus oncoprotein, T-antigen, which has been associated with medulloblastoma and other cancers. JC virus T-antigen localizes predominantly to the nucleus via a classical monopartite nuclear localization signal (NLS). An antibody fragment which recognizes JC virus T-antigen was attached to cross-linked dextran coated iron oxide nanoparticles. Radiolabeled conjugates were added to mouse medulloblastoma cells expressing the target T-antigen to test their ability to bind to tumor cells and be internalized by the cells. All conjugates containing targeting antibody bound to cells and were internalized, with increasing levels over time. There was no difference in cell binding or internalization among conjugates containing 2, 4, 6 or 8 antibody fragments per nanoparticle. Conjugates with only nonspecific antibody on nanoparticles, or unconjugated nonspecific antibody, had significantly lower total binding and internalization than conjugates with targeting antibody. Unconjugated targeting antibody had equivalent or lower cell uptake compared with targeted nanoparticle conjugates. Specificity of uptake was demonstrated by >80% reduction of nanoconjugate uptake in the presence of 100 fold excess of unconjugated antibody. The presence of a membrane translocation peptide (Tat) on the nanoparticles in addition to targeting antibody did not improve nanoconjugate internalization over the internalization caused by the antibody alone. This antibody nanoconjugate demonstrates feasibility of targeting a nuclear protein and suggests that a minimum number of antibody fragments per nanoparticle are sufficient for achieving binding specificity and efficient uptake into living cells.

Keywords: Antibodies; Antigens; Cell Line; Ferrosoferric Oxide; Iodine Radioisotopes; Magnetic Resonance Imaging; Medulloblastoma; Molecular Probes; Monoclonal; Nanoparticles; Neoplasms; Tumor; tumor; viral

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