Evaluation of a PSMA-targeted BNF nanoparticle construct.

Abstract

Early detection enables improved prognosis for prostate cancer (PCa). A promising target for imaging and therapy of PCa is the prostate-specific membrane antigen (PSMA), which exhibits both expression within the epithelium of PCa cells, and becomes internalized upon ligand binding. Here we report the synthesis of a PSMA-targeted bionized nanoferrite (BNF) nanoparticle and its biological evaluation in an experimental model of PCa. The BNF nanoparticle formulation exhibits properties conducive to targeted imaging such as stealth, prolonged circulation time and enhanced clearance from non-target sites. Optical imaging of the targeted BNF in vivo indicates preferential accumulation in PSMA+ tumors 4 h post-injection, suggesting target specificity. On the other hand, non-targeted nanoparticles exhibit lower uptake with similar accumulation in both PSMA+ and PSMA- tumors indicating tumor access without preferential accumulation. Imaging with single photon emission computed tomography (SPECT) and biodistribution studies of a modified construct indicate highest tumor accumulation at 48 h post-injection [4.3 ± 0.4 percentage injected dose per gram of tissue (%ID g(-1))], with tumor/blood and tumor/muscle ratios of 7.5 ± 2.4 and 11.6 ± 1.2 %ID g(-1), respectively. Ex vivo fluorescence microscopy, Prussian blue staining, immunohistochemistry and biodistribution studies confirm enhanced nanoparticle uptake in PSMA+ tumors compared to those not expressing PSMA. The BNF nano-formulation described is promising for PSMA-targeted imaging applications in vivo.

• Authors: Babak Behnam Azad, Sangeeta R Banerjee, Mrudula Pullambhatla, Silvia Lacerda, Catherine A Foss, Yuchuan Wang, Robert Ivkov, Martin G Pomper
• Journal: Nanoscale (Nanoscale) Vol. 7 Issue 10 Pg. 4432-42 (Mar 14 2015) ISSN: 2040-3372 [Electronic] England
• PMID: 25675333 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Surface
• Antineoplastic Agents
• Ferric Compounds
• ferrite
• FOLH1 protein, human
• Glutamate Carboxypeptidase II

Topics

• Animals
• Antigens, Surface (metabolism)
• Antineoplastic Agents (chemistry, pharmacology)
• Cell Line, Tumor
• Drug Delivery Systems (methods)
• Ferric Compounds (chemistry, pharmacology)
• Glutamate Carboxypeptidase II (metabolism)
• Humans
• Male
• Mice
• Nanoparticles (chemistry)
• Prostatic Neoplasms (diagnostic imaging, drug therapy, metabolism)
• Radiography
• Tomography, Emission-Computed, Single-Photon
• Xenograft Model Antitumor Assays