TY - JOUR
T1 - A prostate-specific membrane antigen activated molecular rotor for real-time fluorescence imaging
AU - Zhang, Jingming
AU - Rakhimbekova, Anastasia
AU - Duan, Xiaojiang
AU - Yin, Qingqing
AU - Foss, Catherine A.
AU - Fan, Yan
AU - Xu, Yangyang
AU - Li, Xuesong
AU - Cai, Xuekang
AU - Kutil, Zsofia
AU - Wang, Pengyuan
AU - Yang, Zhi
AU - Zhang, Ning
AU - Pomper, Martin G.
AU - Wang, Yiguang
AU - Bařinka, Cyril
AU - Yang, Xing
N1 - Funding Information:
We thank Barbora Havlinova and Petra Baranova for their excellent technical assistance and Lucia Motlova for help with crystallization experiments. This work was financially supported by the National Natural Science Foundation of China (21877004, 92059101), Clinical Medicine Plus X—Young Scholars Project of Peking University (PKU2020LCXQ029). Additionally, this work was in part supported by the CAS (RVO: 86652036), the Czech Science Foundation (18-04790 S, 19-22269Y) and the National Institutes of Health (R01 CA134675). We acknowledge the Helmholtz-Zentrum Berlin for the allocation of synchrotron radiation beamtime at the MX14.2 beamline and the support by the project CALIPSOplus (grant agreement 730872) from the EU Framework Programme for Research and Innovation HORIZON 2020, and CMS-Biocev (“Crystallization/Diffraction”) supported by MEYS CR (LM2018127).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Surgery is an efficient way to treat localized prostate cancer (PCa), however, it is challenging to demarcate rapidly and accurately the tumor boundary intraoperatively, as existing tumor detection methods are seldom performed in real-time. To overcome those limitations, we develop a fluorescent molecular rotor that specifically targets the prostate-specific membrane antigen (PSMA), an established marker for PCa. The probes have picomolar affinity (IC50= 63-118 pM) for PSMA and generate virtually instantaneous onset of robust fluorescent signal proportional to the concentration of the PSMA-probe complex. In vitro and ex vivo experiments using PCa cell lines and clinical samples, respectively, indicate the utility of the probe for biomedical applications, including real-time monitoring of endocytosis and tumor staging. Experiments performed in a PCa xenograft model reveal suitability of the probe for imaging applications in vivo.
AB - Surgery is an efficient way to treat localized prostate cancer (PCa), however, it is challenging to demarcate rapidly and accurately the tumor boundary intraoperatively, as existing tumor detection methods are seldom performed in real-time. To overcome those limitations, we develop a fluorescent molecular rotor that specifically targets the prostate-specific membrane antigen (PSMA), an established marker for PCa. The probes have picomolar affinity (IC50= 63-118 pM) for PSMA and generate virtually instantaneous onset of robust fluorescent signal proportional to the concentration of the PSMA-probe complex. In vitro and ex vivo experiments using PCa cell lines and clinical samples, respectively, indicate the utility of the probe for biomedical applications, including real-time monitoring of endocytosis and tumor staging. Experiments performed in a PCa xenograft model reveal suitability of the probe for imaging applications in vivo.
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U2 - 10.1038/s41467-021-25746-6
DO - 10.1038/s41467-021-25746-6
M3 - Article
C2 - 34526506
AN - SCOPUS:85115276697
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5460
ER -