Theranostic Agents for Photodynamic Therapy of Prostate Cancer by Targeting Prostate-Specific Membrane Antigen
Autor: | Malcolm E. Kenney, Joseph D. Meyers, Jonathan E. Kiechle, Gopolakrishnan Ramamurthy, Ping Zhang, Lee Ponsky, Brian Tsui, James P. Basilion, Xinning Wang |
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Rok vydání: | 2016 |
Předmět: |
Glutamate Carboxypeptidase II
Male 0301 basic medicine Cancer Research Cell Survival medicine.medical_treatment Antineoplastic Agents Photodynamic therapy Ligands urologic and male genital diseases Theranostic Nanomedicine Mice 03 medical and health sciences Prostate cancer 0302 clinical medicine Prostate Cell Line Tumor medicine Glutamate carboxypeptidase II Animals Humans Amino Acid Sequence Dose-Response Relationship Drug Molecular Structure Prostatectomy business.industry Prostatic Neoplasms Cancer medicine.disease Xenograft Model Antitumor Assays Peptide Fragments Molecular Imaging Tumor Burden Disease Models Animal 030104 developmental biology medicine.anatomical_structure Photochemotherapy Oncology Tumor progression 030220 oncology & carcinogenesis Antigens Surface Cancer cell Cancer research business |
Zdroj: | Molecular Cancer Therapeutics. 15:1834-1844 |
ISSN: | 1538-8514 1535-7163 |
DOI: | 10.1158/1535-7163.mct-15-0722 |
Popis: | Prostatectomy has been the mainstay treatment for men with localized prostate cancer. Surgery, however, often can result in major side effects, which are caused from damage and removal of nerves and muscles surrounding the prostate. A technology that can help surgeons more precisely identify and remove prostate cancer resulting in a more complete prostatectomy is needed. Prostate-specific membrane antigen (PSMA), a type II membrane antigen highly expressed in prostate cancer, has been an attractive target for imaging and therapy. The objective of this study is to develop low molecular weight PSMA-targeted photodynamic therapy (PDT) agents, which would provide image guidance for prostate tumor resection and allow for subsequent PDT to eliminate unresectable or remaining cancer cells. On the basis of our highly negatively charged, urea-based PSMA ligand PSMA-1, we synthesized two PSMA-targeting PDT conjugates named PSMA-1-Pc413 and PSMA-1-IR700. In in vitro cellular uptake experiments and in vivo animal imaging experiments, the two conjugates demonstrated selective and specific uptake in PSMA-positive PC3pip cells/tumors, but not in PSMA-negative PC3flu cells/tumors. Further in vivo photodynamic treatment proved that the two PSMA-1–PDT conjugates can effectively inhibit PC3pip tumor progression. The two PSMA-1–PDT conjugates reported here may have the potential to aid in the detection and resection of prostate cancers. It may also allow for the identification of unresectable cancer tissue and PDT ablation of such tissue after surgical resection with potentially less damage to surrounding tissues. Mol Cancer Ther; 15(8); 1834–44. ©2016 AACR. |
Databáze: | OpenAIRE |
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