title: 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.
authors.affiliation: The Brady Urological Institute & Department of Urology, The Johns Hopkins School of Medicine, 600 N Wolfe St., Baltimore, MD (USA).
authors.forename: Amarnath
authors.initials: A
authors.lastname: Mukherjee
authors.forename: Thomas
authors.initials: T
authors.lastname: Darlington
authors.forename: Richard
authors.initials: R
authors.lastname: Baldwin
authors.forename: Charles
authors.initials: C
authors.lastname: Holz
authors.forename: Sage
authors.initials: S
authors.lastname: Olson
authors.forename: Prakash
authors.initials: P
authors.lastname: Kulkarni
authors.forename: Theodore L
authors.initials: TL
authors.lastname: DeWeese
authors.forename: Robert H
authors.initials: RH
authors.lastname: Getzenberg
authors.forename: Robert
authors.initials: R
authors.lastname: Ivkov
authors.forename: Shawn E
authors.initials: SE
authors.lastname: Lupold
mesh_terms: D055910:Antibodies, Immobilized / Q000737:chemistry / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005290:Ferric Compounds / Q000737:chemistry*; D006801:Humans; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D017430:Prostate-Specific Antigen / Q000032:analysis* / Q000276:immunology; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D055910:Antibodies, Immobilized; D000911:Antibodies, Monoclonal; D005290:Ferric Compounds; C000499:ferric oxide; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D017430:Prostate-Specific Antigen
keywords: cancer; iron oxide; nanoparticles; prostate-specific membrane antigens; targeting