title: PSMA-targeted theranostic nanoplex for prostate cancer therapy.
abstract: Theranostic imaging, where diagnosis is combined with therapy, is particularly suitable for a disease that is as complex as cancer, especially now that genomic and proteomic profiling can provide an extensive "fingerprint" of each tumor. With such information, theranostic agents can be designed to personalize treatment and minimize damage to normal tissue. Here we have developed a nanoplex platform for theranostic imaging of prostate cancer (PCa). In these proof-of-principle studies, a therapeutic nanoplex containing multimodal imaging reporters was targeted to prostate-specific membrane antigen (PSMA), which is expressed on the cell surface of castrate-resistant PCa. The nanoplex was designed to deliver small interfering RNA (siRNA) along with a prodrug enzyme to PSMA-expressing tumors. Each component of the nanoplex was carefully selected to evaluate its diagnostic aspect of PSMA imaging and its therapeutic aspects of siRNA-mediated down-regulation of a target gene and the conversion of a prodrug to cytotoxic drug, using noninvasive multimodality imaging. Studies performed using two variants of human PC3-PCa cells and tumors, one with high PSMA expression level and another with negligible expression levels, demonstrated PSMA-specific uptake. In addition, down-regulation of the selected siRNA target, choline kinase (Chk), and the conversion of the nontoxic prodrug 5-fluorocytosine (5-FC) to cytotoxic 5-fluorouracil (5-FU) were also demonstrated with noninvasive imaging. The nanoplex was well-tolerated and did not induce liver or kidney toxicity or a significant immune response. The nanoplex platform described can be easily modified and applied to different cancers, receptors, and pathways to achieve theranostic imaging, as a single agent or in combination with other treatment modalities.
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science.
authors.forename: Zhihang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Penet
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science.|Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Nimmagadda
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science.
authors.forename: Sangeeta R
authors.initials: SR
authors.lastname: Banerjee
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Winnard
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science.|Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Artemov
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science.|Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.
authors.forename: Kristine
authors.initials: K
authors.lastname: Glunde
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science.|Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.affiliation: JHU ICMIC Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science.|Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.
authors.forename: Zaver M
authors.initials: ZM
authors.lastname: Bhujwalla
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D009928:Organ Specificity; D017430:Prostate-Specific Antigen / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy*; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D017430:Prostate-Specific Antigen