1. PSMA-specific theranostic nanoplex for combination of TRAIL gene and 5-FC prodrug therapy of prostate cancer.
- Author
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Chen Z, Penet MF, Krishnamachary B, Banerjee SR, Pomper MG, and Bhujwalla ZM
- Subjects
- Animals, Antigens, Surface metabolism, Antimetabolites metabolism, Antimetabolites therapeutic use, Bacteria enzymology, Cell Line, Tumor, Cytosine Deaminase administration & dosage, Cytosine Deaminase metabolism, Cytosine Deaminase therapeutic use, DNA genetics, DNA therapeutic use, Enzyme Therapy, Flucytosine metabolism, Flucytosine therapeutic use, Genetic Therapy, Glutamate Carboxypeptidase II metabolism, Humans, Male, Mice, Models, Molecular, Plasmids administration & dosage, Plasmids genetics, Plasmids therapeutic use, Prodrugs metabolism, Prodrugs therapeutic use, Prostate drug effects, Prostate metabolism, Prostate pathology, Prostatic Neoplasms metabolism, Prostatic Neoplasms pathology, Theranostic Nanomedicine, Antimetabolites administration & dosage, DNA administration & dosage, Drug Delivery Systems, Flucytosine administration & dosage, Prodrugs administration & dosage, Prostatic Neoplasms therapy, TNF-Related Apoptosis-Inducing Ligand genetics
- Abstract
Metastatic prostate cancer causes significant morbidity and mortality and there is a critical unmet need for effective treatments. We have developed a theranostic nanoplex platform for combined imaging and therapy of prostate cancer. Our prostate-specific membrane antigen (PSMA) targeted nanoplex is designed to deliver plasmid DNA encoding tumor necrosis factor related apoptosis-inducing ligand (TRAIL), together with bacterial cytosine deaminase (bCD) as a prodrug enzyme. Nanoplex specificity was tested using two variants of human PC3 prostate cancer cells in culture and in tumor xenografts, one with high PSMA expression and the other with negligible expression levels. The expression of EGFP-TRAIL was demonstrated by fluorescence optical imaging and real-time PCR. Noninvasive (19)F MR spectroscopy detected the conversion of the nontoxic prodrug 5-fluorocytosine (5-FC) to cytotoxic 5-fluorouracil (5-FU) by bCD. The combination strategy of TRAIL gene and 5-FC/bCD therapy showed significant inhibition of the growth of prostate cancer cells and tumors. These data demonstrate that the PSMA-specific theranostic nanoplex can deliver gene therapy and prodrug enzyme therapy concurrently for precision medicine in metastatic prostate cancer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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