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
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