A cell-impermeable luminogenic probe for near-infrared imaging of prostate-specific membrane antigen in prostate cancer microenvironments
Copyright © 2023 Elsevier Masson SAS. All rights reserved..
Prostate-specific membrane antigen (PSMA) imaging probes are a promising tool for the diagnosis and image-guided surgery of prostate cancer (PCa). However, PSMA-specific luminescence probes for PCa detection and heterogeneity studies with high imaging contrast are lacking. Here, we report the first near-infrared (NIR) iridium(III) complex for the wash-free and specific imaging of PSMA in PCa cells and spheroids. The conjugation of a PSMA inhibitor, Lys-urea-Glu, to an iridium(III) complex synergizes the PSMA-specific affinity and biocompatibility of the inhibitor with the desirable photophysical properties of the iridium(III) complex, including NIR emission (670 nm), high photostability and a large Stokes shift. The cellular impermeability of the probe along with its strong binding affinity to PSMA enhances its specificity for PSMA, enabling the washing-free luminescent imaging of membrane PSMA with lower cytotoxicity. The probe was successfully applied for selectively visualizing PSMA-expressing cells and for the imaging of PSMA in a multicellular PCa model with good imaging penetration, indicating its potential use in complicated and heterogeneous tumor microenvironments. Furthermore, the probe showed good imaging performance in the PCa-bearing tumor mice via targeting PSMA in vivo. This work provides a novel strategy for the development of highly sensitive and specific NIR probes for PSMA in biological systems in vitro, which is of great significance for the precise diagnosis of PCa and for elucidating PCa heterogeneity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:259 |
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| Enthalten in: |
European journal of medicinal chemistry - 259(2023) vom: 05. Nov., Seite 115659 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yang, Xifang [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.08.2023 Date Revised 22.08.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejmech.2023.115659 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Prostate-specific membrane antigen (PSMA) imaging probes are a promising tool for the diagnosis and image-guided surgery of prostate cancer (PCa). However, PSMA-specific luminescence probes for PCa detection and heterogeneity studies with high imaging contrast are lacking. Here, we report the first near-infrared (NIR) iridium(III) complex for the wash-free and specific imaging of PSMA in PCa cells and spheroids. The conjugation of a PSMA inhibitor, Lys-urea-Glu, to an iridium(III) complex synergizes the PSMA-specific affinity and biocompatibility of the inhibitor with the desirable photophysical properties of the iridium(III) complex, including NIR emission (670 nm), high photostability and a large Stokes shift. The cellular impermeability of the probe along with its strong binding affinity to PSMA enhances its specificity for PSMA, enabling the washing-free luminescent imaging of membrane PSMA with lower cytotoxicity. The probe was successfully applied for selectively visualizing PSMA-expressing cells and for the imaging of PSMA in a multicellular PCa model with good imaging penetration, indicating its potential use in complicated and heterogeneous tumor microenvironments. Furthermore, the probe showed good imaging performance in the PCa-bearing tumor mice via targeting PSMA in vivo. This work provides a novel strategy for the development of highly sensitive and specific NIR probes for PSMA in biological systems in vitro, which is of great significance for the precise diagnosis of PCa and for elucidating PCa heterogeneity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cell impermeability | |
| 650 | 4 | |a Iridium(III) complex | |
| 650 | 4 | |a Luminogenic probe | |
| 650 | 4 | |a NIR | |
| 650 | 4 | |a Prostate cancer | |
| 650 | 4 | |a Prostate-specific membrane antigen | |
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| 700 | 1 | |a Kong, Lingtan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Ko, Chung-Nga |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jinbiao |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Dik-Lung |e verfasserin |4 aut | |
| 700 | 1 | |a Leung, Chung-Hang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Wanhe |e verfasserin |4 aut | |
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