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De novo design of a novel AIE fluorescent probe tailored to autophagy visualization via pH manipulation
BACKGROUND: Macroautophagy is an essential cellular self-protection mechanism, and defective autophagy has been considered to contribute to a variety of diseases. During the process, cytoplasmic components are transported via autophagosomes to acidic lysosomes for metabolism and recycling, which rep...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10012510/ https://www.ncbi.nlm.nih.gov/pubmed/36915215 http://dx.doi.org/10.1186/s40824-023-00359-w |
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author | Huang, Xueyan Chen, Fei Ma, Yeshuo Zheng, Fan Fang, Yanpeng Feng, Bin Huang, Shuai Zeng, Hongliang Zeng, Wenbin |
author_facet | Huang, Xueyan Chen, Fei Ma, Yeshuo Zheng, Fan Fang, Yanpeng Feng, Bin Huang, Shuai Zeng, Hongliang Zeng, Wenbin |
author_sort | Huang, Xueyan |
collection | PubMed |
description | BACKGROUND: Macroautophagy is an essential cellular self-protection mechanism, and defective autophagy has been considered to contribute to a variety of diseases. During the process, cytoplasmic components are transported via autophagosomes to acidic lysosomes for metabolism and recycling, which represents application niches for lysosome-targeted fluorescent probes. Additionally, in view of the complexity of the autophagy pathway, it entails more stringent requirements for probes suitable for monitoring autophagy. Meanwhile, aggregation-induced emission (AIE) fluorescent probes have been impressively demonstrated in the biomedical field, which bring fascinating possibilities to the autophagy visualization. METHODS: We reported a generalizable de novo design of a novel pH-sensitive AIE probe ASMP-AP tailored to lysosome targeting for the interpretation of autophagy. Firstly, the theoretical calculation was carried out followed by the investigation of optical properties. Then, the performance of ASMP-AP in visualizing autophagy was corroborated by starvation or drugs treatments. Furthermore, the capability of ASMP-AP to monitor autophagy was demonstrated in ex vivo liver tissue and zebrafish in vivo. RESULTS: ASMP-AP displays a large stokes shift, great cell permeability and good biocompatibility. More importantly, ASMP-AP enables a good linear response to pH, which derives from the fact that its aggregation state can be manipulated by the acidity. It was successfully applied for imaging autophagy in living cells and was proved capable of monitoring mitophagy. Moreover, this novel molecular tool was validated by ex vivo visualization of activated autophagy in drug-induced liver injury model. Interestingly, it provided a meaningful pharmacological insight that the melanin inhibitor 1-phenyl-2-thiourea (PTU)-induced autophagy was clearly presented in wild-type zebrafish. CONCLUSIONS: ASMP-AP offers a simple yet effective tool for studying lysosome and autophagy. This is the first instance to visualize autophagy in zebrafish using a small-molecule probe with AIE characters, accurate lysosome targeting and simultaneous pH sensitivity. Ultimately, this novel fluorescent system has great potential for in vivo translation to fuel autophagy research. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40824-023-00359-w. |
format | Online Article Text |
id | pubmed-10012510 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-100125102023-03-15 De novo design of a novel AIE fluorescent probe tailored to autophagy visualization via pH manipulation Huang, Xueyan Chen, Fei Ma, Yeshuo Zheng, Fan Fang, Yanpeng Feng, Bin Huang, Shuai Zeng, Hongliang Zeng, Wenbin Biomater Res Research Article BACKGROUND: Macroautophagy is an essential cellular self-protection mechanism, and defective autophagy has been considered to contribute to a variety of diseases. During the process, cytoplasmic components are transported via autophagosomes to acidic lysosomes for metabolism and recycling, which represents application niches for lysosome-targeted fluorescent probes. Additionally, in view of the complexity of the autophagy pathway, it entails more stringent requirements for probes suitable for monitoring autophagy. Meanwhile, aggregation-induced emission (AIE) fluorescent probes have been impressively demonstrated in the biomedical field, which bring fascinating possibilities to the autophagy visualization. METHODS: We reported a generalizable de novo design of a novel pH-sensitive AIE probe ASMP-AP tailored to lysosome targeting for the interpretation of autophagy. Firstly, the theoretical calculation was carried out followed by the investigation of optical properties. Then, the performance of ASMP-AP in visualizing autophagy was corroborated by starvation or drugs treatments. Furthermore, the capability of ASMP-AP to monitor autophagy was demonstrated in ex vivo liver tissue and zebrafish in vivo. RESULTS: ASMP-AP displays a large stokes shift, great cell permeability and good biocompatibility. More importantly, ASMP-AP enables a good linear response to pH, which derives from the fact that its aggregation state can be manipulated by the acidity. It was successfully applied for imaging autophagy in living cells and was proved capable of monitoring mitophagy. Moreover, this novel molecular tool was validated by ex vivo visualization of activated autophagy in drug-induced liver injury model. Interestingly, it provided a meaningful pharmacological insight that the melanin inhibitor 1-phenyl-2-thiourea (PTU)-induced autophagy was clearly presented in wild-type zebrafish. CONCLUSIONS: ASMP-AP offers a simple yet effective tool for studying lysosome and autophagy. This is the first instance to visualize autophagy in zebrafish using a small-molecule probe with AIE characters, accurate lysosome targeting and simultaneous pH sensitivity. Ultimately, this novel fluorescent system has great potential for in vivo translation to fuel autophagy research. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40824-023-00359-w. BioMed Central 2023-03-13 /pmc/articles/PMC10012510/ /pubmed/36915215 http://dx.doi.org/10.1186/s40824-023-00359-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Huang, Xueyan Chen, Fei Ma, Yeshuo Zheng, Fan Fang, Yanpeng Feng, Bin Huang, Shuai Zeng, Hongliang Zeng, Wenbin De novo design of a novel AIE fluorescent probe tailored to autophagy visualization via pH manipulation |
title | De novo design of a novel AIE fluorescent probe tailored to autophagy visualization via pH manipulation |
title_full | De novo design of a novel AIE fluorescent probe tailored to autophagy visualization via pH manipulation |
title_fullStr | De novo design of a novel AIE fluorescent probe tailored to autophagy visualization via pH manipulation |
title_full_unstemmed | De novo design of a novel AIE fluorescent probe tailored to autophagy visualization via pH manipulation |
title_short | De novo design of a novel AIE fluorescent probe tailored to autophagy visualization via pH manipulation |
title_sort | de novo design of a novel aie fluorescent probe tailored to autophagy visualization via ph manipulation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10012510/ https://www.ncbi.nlm.nih.gov/pubmed/36915215 http://dx.doi.org/10.1186/s40824-023-00359-w |
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