PSMA-Targeted PAMAM Dendrimers for Specific Delivery of Imaging, Contrast and Therapeutic Agents

Unmet Need
According to The American Cancer Society, approximately 1 in 9 men will be diagnosed with prostate cancer in their lifetime, with 174,650 new cases diagnosed yearly in the US.  As prostate cancer is the second leading cause of cancer death in American men, early detection is important for adequate treatment.  The most common method of detecting prostate cancer remains the prostate-specific antigen (PSA) blood test.  However, current PSA testing has a well-known limitation, i.e., a low PSA number can miss potential prostate cancers, while a high PSA can lead to false positives in which no prostate cancer is diagnosed.  As such, new approaches are needed to further improve prostate cancer test detection, accuracy and reliability.
 
Technology Overview
Johns Hopkins researchers recently developed a 4th-generation PSA test, and a method of synthesis, based on the prostate-specific membrane antigen (PSMA), which is expressed in all types of prostate tissue and increased PSMA expression in cancer tissue.  Polyamidoamine (PAMAM) dendrimers are emerging as a versatile platform for drug delivery due to their unique physicochemical properties.  Data with PSMA-targeted PAMAM dendrimers (G4-PSMA) nanoparticles demonstrated high accumulation and retention in PSMA-positive tumors in animal models with relatively low uptake in off-target tissues.  Moreover, the dendrimer particles were eliminated naturally via renal clearance.  Altogether, results indicate that G4-PSMA represents a suitable scaffold by which to target PSMA-expressing tissues with imaging/contrast, photodynamic therapy agents, silver and gold metallic nanoclusters, and other therapeutic agents.
 
Stage of Development
In vitro and in vivo animal model data are available.

Publications
Manuscript in preparation.
 

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