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

Amarnath Mukherjee, Thomas Darlington, Richard Baldwin, Charles Holz, Sage Olson, Prakash Kulkarni, Theodore L. Deweese, Robert H. Getzenberg, Robert Ivkov, Shawn E. Lupold

Research output: Contribution to journalArticle

16 Scopus citations

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. Targeted MIONs: Silica-coated antibody-conjugated iron oxide nanoparticles were prepared, and their ability to specifically target prostate-specific membrane antigen (PSMA), a validated target in prostate cancer, was evaluated using iron spectral absorbance and enzyme-linked immunoassay (ELISA).

Original languageEnglish (US)
Pages (from-to)1356-1360
Number of pages5
JournalChemMedChem
Volume9
Issue number7
DOIs
Publication statusPublished - Jul 2014
Externally publishedYes

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Keywords

  • cancer
  • iron oxide
  • nanoparticles
  • prostate-specific membrane antigens
  • targeting

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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