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A “Double-Locked” and Enzyme/pH-Activated Theranostic Agent for Accurate Tumor Imaging and Therapy

Theranostic agents for concurrent cancer therapy and diagnosis have begun attracting attention as a promising modality. However, accurate imaging and identification remains a great challenge for theranostic agents. Here, we designed and synthesized a novel theranostic agent H6M based on the “double-...

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Autores principales: Luo, Jia, Guan, Zongyu, Gao, Weijie, Wang, Chen, Xu, Zhongyuan, Meng, Chi, Liu, Yun, Zhang, Yuquan, Guo, Qingsong, Ling, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779152/
https://www.ncbi.nlm.nih.gov/pubmed/35056740
http://dx.doi.org/10.3390/molecules27020425
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author Luo, Jia
Guan, Zongyu
Gao, Weijie
Wang, Chen
Xu, Zhongyuan
Meng, Chi
Liu, Yun
Zhang, Yuquan
Guo, Qingsong
Ling, Yong
author_facet Luo, Jia
Guan, Zongyu
Gao, Weijie
Wang, Chen
Xu, Zhongyuan
Meng, Chi
Liu, Yun
Zhang, Yuquan
Guo, Qingsong
Ling, Yong
author_sort Luo, Jia
collection PubMed
description Theranostic agents for concurrent cancer therapy and diagnosis have begun attracting attention as a promising modality. However, accurate imaging and identification remains a great challenge for theranostic agents. Here, we designed and synthesized a novel theranostic agent H6M based on the “double-locked” strategy by introducing an electron-withdrawing nitro group into 1-position of a pH-responsive 3-amino-β-carboline and further covalently linking the hydroxamic acid group, a zinc-binding group (ZBG), to the 3-position of β-carboline to obtain histone deacetylase (HDAC) inhibitory effect for combined HDAC-targeted therapy. We found that H6M can be specifically reduced under overexpressed nitroreductase (NTR) to produce H6AQ, which emits bright fluorescence at low pH. Notably, H6M demonstrated a selective fluorescence imaging via successive reactions with NTR (first “key”) and pH (second “key”), and precisely identified tumor margins with a high S/N ratio to guide tumor resection. Finally, H6M exerted robust HDAC1/cancer cell inhibitory activities compared with a known HDAC inhibitor SAHA. Therefore, the NTR/pH-activated theranostic agent provided a novel tool for precise diagnosis and efficient tumor therapy.
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spelling pubmed-87791522022-01-22 A “Double-Locked” and Enzyme/pH-Activated Theranostic Agent for Accurate Tumor Imaging and Therapy Luo, Jia Guan, Zongyu Gao, Weijie Wang, Chen Xu, Zhongyuan Meng, Chi Liu, Yun Zhang, Yuquan Guo, Qingsong Ling, Yong Molecules Article Theranostic agents for concurrent cancer therapy and diagnosis have begun attracting attention as a promising modality. However, accurate imaging and identification remains a great challenge for theranostic agents. Here, we designed and synthesized a novel theranostic agent H6M based on the “double-locked” strategy by introducing an electron-withdrawing nitro group into 1-position of a pH-responsive 3-amino-β-carboline and further covalently linking the hydroxamic acid group, a zinc-binding group (ZBG), to the 3-position of β-carboline to obtain histone deacetylase (HDAC) inhibitory effect for combined HDAC-targeted therapy. We found that H6M can be specifically reduced under overexpressed nitroreductase (NTR) to produce H6AQ, which emits bright fluorescence at low pH. Notably, H6M demonstrated a selective fluorescence imaging via successive reactions with NTR (first “key”) and pH (second “key”), and precisely identified tumor margins with a high S/N ratio to guide tumor resection. Finally, H6M exerted robust HDAC1/cancer cell inhibitory activities compared with a known HDAC inhibitor SAHA. Therefore, the NTR/pH-activated theranostic agent provided a novel tool for precise diagnosis and efficient tumor therapy. MDPI 2022-01-10 /pmc/articles/PMC8779152/ /pubmed/35056740 http://dx.doi.org/10.3390/molecules27020425 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Luo, Jia
Guan, Zongyu
Gao, Weijie
Wang, Chen
Xu, Zhongyuan
Meng, Chi
Liu, Yun
Zhang, Yuquan
Guo, Qingsong
Ling, Yong
A “Double-Locked” and Enzyme/pH-Activated Theranostic Agent for Accurate Tumor Imaging and Therapy
title A “Double-Locked” and Enzyme/pH-Activated Theranostic Agent for Accurate Tumor Imaging and Therapy
title_full A “Double-Locked” and Enzyme/pH-Activated Theranostic Agent for Accurate Tumor Imaging and Therapy
title_fullStr A “Double-Locked” and Enzyme/pH-Activated Theranostic Agent for Accurate Tumor Imaging and Therapy
title_full_unstemmed A “Double-Locked” and Enzyme/pH-Activated Theranostic Agent for Accurate Tumor Imaging and Therapy
title_short A “Double-Locked” and Enzyme/pH-Activated Theranostic Agent for Accurate Tumor Imaging and Therapy
title_sort “double-locked” and enzyme/ph-activated theranostic agent for accurate tumor imaging and therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779152/
https://www.ncbi.nlm.nih.gov/pubmed/35056740
http://dx.doi.org/10.3390/molecules27020425
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