Targeting prostate cancer cells with PSMA inhibitor-guided gold nanoparticles

Prostate-specific membrane antigen (PSMA) is a notable biomarker for diagnostic and therapeutic applications in prostate cancer. Gold nanoparticles (AuNPs) provide an attractive nanomaterial platform for combining a variety of targeting, imaging, and cytotoxic agents into a unified device for biomed...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2013-01, Vol.23 (2), p.565-568
Main Authors: Kasten, Benjamin B, Liu, Tiancheng, Nedrow-Byers, Jessie R, Benny, Paul D, Berkman, Clifford E
Format: Article
Language:English
Subjects:
antigens
Antigens, Surface - metabolism
Bacterial Proteins - chemistry
biomarkers
biomedical research
Biotin - analogs & derivatives
Biotin - chemistry
Cell Line, Tumor
chemistry
Cytotoxic agents
cytotoxicity
Drug Delivery Systems
Glutamate Carboxypeptidase II - antagonists & inhibitors
Glutamate Carboxypeptidase II - metabolism
Gold
Gold - chemistry
Gold - pharmacology
Gold - therapeutic use
Humans
image analysis
imaging
in vitro studies
Male
medical equipment
Metal Nanoparticles - chemistry
Metal Nanoparticles - therapeutic use
nanogold
nanoparticles
peptidomimetics
Prostate cancer
prostatic neoplasms
Prostatic Neoplasms - drug therapy
Protein Binding - drug effects
Therapeutic applications
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Summary:Prostate-specific membrane antigen (PSMA) is a notable biomarker for diagnostic and therapeutic applications in prostate cancer. Gold nanoparticles (AuNPs) provide an attractive nanomaterial platform for combining a variety of targeting, imaging, and cytotoxic agents into a unified device for biomedical research. In this study, we present the generation and evaluation of the first AuNP system functionalized with a small molecule phosphoramidate peptidomimetic inhibitor for the targeted delivery to PSMA-expressing prostate cancer cells. The general approach involved the conjugation of streptavidin-coated AuNPs with a biotin-linked PSMA inhibitor (CTT54) to generate PSMA-targeted AuNPs. In vitro evaluations of these targeted AuNPs were conducted to determine PSMA-mediated and time-dependent binding to PSMA-positive LNCaP cells. The PSMA-targeted AuNPs exhibited significantly higher and selective binding to LNCaP cells compared to control non-targeted AuNPs, thus demonstrating the feasibility of this approach.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2012.11.015