0 101

Cited 0 times in

Synthesis and Evaluation of Multifunctional Fluorescent Inhibitors with Synergistic Interaction of Prostate-Specific Membrane Antigen and Hypoxia for Prostate Cancer

Authors
 Young-Do Kwon  ;  Jung-Mi Oh  ;  Minh Thanh La  ;  Hea-Jong Chung  ;  Sun Joo Lee  ;  Sungkun Chun  ;  Sun-Hwa Lee  ;  Byung-Hoon Jeong  ;  Hee-Kwon Kim 
Citation
 BIOCONJUGATE CHEMISTRY, Vol.30(1) : 90-100, 2019-01 
Journal Title
BIOCONJUGATE CHEMISTRY
ISSN
 1043-1802 
Issue Date
2019-01
MeSH
Animals ; Antigens, Surface / metabolism* ; Cell Hypoxia* ; Cell Line, Tumor ; Female ; Fluorescent Dyes / chemical synthesis* ; Fluorescent Dyes / chemistry ; Fluorescent Dyes / metabolism* ; Glutamate Carboxypeptidase II / metabolism* ; Glutamic Acid / chemistry ; Heterografts ; Humans ; Lysine / chemistry ; Male ; Mice ; Mice, Inbred BALB C ; Prostatic Neoplasms / metabolism* ; Prostatic Neoplasms / pathology ; Tissue Distribution ; Urea / chemistry
Abstract
Prostate cancer is one of the most common cancers in the world. It is widely known that prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer, and hypoxia is a common characteristic of many solid tumors, including prostate cancer. In this study, we designed multifunctional fluorescent inhibitors to target PSMA and tumor hypoxia in order to increase the tumor uptake of inhibitors. Novel PSMA inhibitors were prepared using lysine as the backbone to connect three different functional groups: the glutamate-urea-lysine (GUL) structure for inhibiting PSMA, 2-nitroimidazole for the hypoxia-sensitive moiety, and a near-infrared fluorophore (sulfo-Cyanine 5.5). According to the in vitro PSMA binding assay, novel fluorescent inhibitors were demonstrated to have nanomolar binding affinities. Multifunctional inhibitor 2 with one 2-nitroimidazole had a similar inhibitory activity to inhibitor 1 that did not contain the hypoxia targeting moiety, but multifunctional inhibitor 3 with two 2-nitroimidazoles showed lower inhibitory activity than inhibitor 1 due to the bulky structure of the hypoxia-sensitive group. However, in vivo optical imaging and ex vivo biodistribution studies indicated that both multifunctional inhibitors 2 and 3 had higher accumulation in tumors than inhibitor 1 due to a synergistic combination of PSMA and hypoxia targeting moieties. These observations suggest that this novel multifunctional strategy might be a promising approach to improve the diagnosis and therapy of prostate cancer.
Full Text
https://pubs.acs.org/doi/10.1021/acs.bioconjchem.8b00767
DOI
10.1021/acs.bioconjchem.8b00767
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/189110
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links