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Development and screening of a series of antibody-conjugated and silica-coated iron oxide nanoparticles for targeting the prostate-specific membrane antigen.

Abstract
The prostate-specific membrane antigen (PSMA) is an established target for the delivery of cancer therapeutic and imaging agents due to its high expression on the surface of prostate cancer cells and within the neovasculature of other solid tumors. Here, we describe the synthesis and screening of antibody-conjugated silica-coated iron oxide nanoparticles for PSMA-specific cell targeting. The humanized anti-PSMA antibody, HuJ591, was conjugated to a series of nanoparticles with varying densities of polyethylene glycol and primary amine groups. Customized assays utilizing iron spectral absorbance and enzyme-linked immunoassay (ELISA) were developed to screen microgram quantities of nanoparticle formulations for immunoreactivity and cell targeting ability. Antibody and PSMA-specific targeting of the optimized nanoparticle was evaluated using an isogenic PSMA-positive and PSMA-negative cell line pair. Specific nanoparticle targeting was confirmed by iron quantification with inductively coupled plasma mass spectrometry (ICP-MS). These methods and nanoparticles support the promise of targeted theranostic agents for future treatment of prostate and other cancers.
AuthorsAmarnath Mukherjee, Thomas Darlington, Richard Baldwin, Charles Holz, Sage Olson, Prakash Kulkarni, Theodore L DeWeese, Robert H Getzenberg, Robert Ivkov, Shawn E Lupold
JournalChemMedChem (ChemMedChem) Vol. 9 Issue 7 Pg. 1356-60 (Jul 2014) ISSN: 1860-7187 [Electronic] Germany
PMID24591351 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Chemical References
  • Antibodies, Immobilized
  • Antibodies, Monoclonal
  • Ferric Compounds
  • ferric oxide
  • Polyethylene Glycols
  • Silicon Dioxide
  • Prostate-Specific Antigen
Topics
  • Antibodies, Immobilized (chemistry, immunology)
  • Antibodies, Monoclonal (chemistry, immunology)
  • Cell Line, Tumor
  • Enzyme-Linked Immunosorbent Assay
  • Ferric Compounds (chemistry)
  • Humans
  • Male
  • Nanoparticles (chemistry)
  • Polyethylene Glycols (chemistry)
  • Prostate-Specific Antigen (analysis, immunology)
  • Silicon Dioxide (chemistry)

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