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Diketopyrrolopyrrole-based fluorescence probes for the imaging of lysosomal Zn(2+) and identification of prostate cancer in human tissue
A series of diketopyrrolopyrrole-based fluorescent probes (DPP-C2, LysoDPP-C2, LysoDPP-C3, and LysoDPP-C4) have been developed for the detection of low pH and Zn(2+) in an AND logic fashion. The chelation of Zn(2+) or the protonation of a morpholine moiety within these probes results in a partial in...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Royal Society of Chemistry
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6568042/ https://www.ncbi.nlm.nih.gov/pubmed/31293754 http://dx.doi.org/10.1039/c9sc01153f |
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author | Du, Chenchen Fu, Shibo Wang, Xiaohua Sedgwick, Adam C. Zhen, Wei Li, Minjie Li, Xinqiang Zhou, Juan Wang, Zhong Wang, Hongyu Sessler, Jonathan L. |
author_facet | Du, Chenchen Fu, Shibo Wang, Xiaohua Sedgwick, Adam C. Zhen, Wei Li, Minjie Li, Xinqiang Zhou, Juan Wang, Zhong Wang, Hongyu Sessler, Jonathan L. |
author_sort | Du, Chenchen |
collection | PubMed |
description | A series of diketopyrrolopyrrole-based fluorescent probes (DPP-C2, LysoDPP-C2, LysoDPP-C3, and LysoDPP-C4) have been developed for the detection of low pH and Zn(2+) in an AND logic fashion. The chelation of Zn(2+) or the protonation of a morpholine moiety within these probes results in a partial increase in the fluorescence intensity, an effect ascribed to suppression of one possible photo-induced electron transfer (PET) pathway. In contrast, a large increase in the observed fluorescence intensity is observed at low pH and in the presence of Zn(2+); this is rationalized in terms of both possible PET pathways within the probes being blocked. Job plots, fluorescence titration curves, and isothermal titration calorimetry proved consistent with a 1 : 1 Zn(2+) complexation stoichiometry. Each probe demonstrated an excellent selectivity towards Zn(2+) and the resulting Zn(2+) complexes demonstrated pH sensitivity over the 3.5–9 pH range. Fluorescence imaging experiments confirmed that LysoDPP-C4 was capable of imaging lysosomal Zn(2+) in live cells. Little evidence of cytotoxicity was seen. LysoDPP-C4 was successfully applied to the bioimaging of nude mice, wherein it was shown capable of imaging the prostate. Histological studies using a human sample revealed that LysoDPP-C4 can discriminate cancerous prostate tissue from healthy prostate tissue. |
format | Online Article Text |
id | pubmed-6568042 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-65680422019-07-10 Diketopyrrolopyrrole-based fluorescence probes for the imaging of lysosomal Zn(2+) and identification of prostate cancer in human tissue Du, Chenchen Fu, Shibo Wang, Xiaohua Sedgwick, Adam C. Zhen, Wei Li, Minjie Li, Xinqiang Zhou, Juan Wang, Zhong Wang, Hongyu Sessler, Jonathan L. Chem Sci Chemistry A series of diketopyrrolopyrrole-based fluorescent probes (DPP-C2, LysoDPP-C2, LysoDPP-C3, and LysoDPP-C4) have been developed for the detection of low pH and Zn(2+) in an AND logic fashion. The chelation of Zn(2+) or the protonation of a morpholine moiety within these probes results in a partial increase in the fluorescence intensity, an effect ascribed to suppression of one possible photo-induced electron transfer (PET) pathway. In contrast, a large increase in the observed fluorescence intensity is observed at low pH and in the presence of Zn(2+); this is rationalized in terms of both possible PET pathways within the probes being blocked. Job plots, fluorescence titration curves, and isothermal titration calorimetry proved consistent with a 1 : 1 Zn(2+) complexation stoichiometry. Each probe demonstrated an excellent selectivity towards Zn(2+) and the resulting Zn(2+) complexes demonstrated pH sensitivity over the 3.5–9 pH range. Fluorescence imaging experiments confirmed that LysoDPP-C4 was capable of imaging lysosomal Zn(2+) in live cells. Little evidence of cytotoxicity was seen. LysoDPP-C4 was successfully applied to the bioimaging of nude mice, wherein it was shown capable of imaging the prostate. Histological studies using a human sample revealed that LysoDPP-C4 can discriminate cancerous prostate tissue from healthy prostate tissue. Royal Society of Chemistry 2019-05-01 /pmc/articles/PMC6568042/ /pubmed/31293754 http://dx.doi.org/10.1039/c9sc01153f Text en This journal is © The Royal Society of Chemistry 2019 http://creativecommons.org/licenses/by-nc/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported Licence (CC BY-NC 3.0) |
spellingShingle | Chemistry Du, Chenchen Fu, Shibo Wang, Xiaohua Sedgwick, Adam C. Zhen, Wei Li, Minjie Li, Xinqiang Zhou, Juan Wang, Zhong Wang, Hongyu Sessler, Jonathan L. Diketopyrrolopyrrole-based fluorescence probes for the imaging of lysosomal Zn(2+) and identification of prostate cancer in human tissue |
title | Diketopyrrolopyrrole-based fluorescence probes for the imaging of lysosomal Zn(2+) and identification of prostate cancer in human tissue
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title_full | Diketopyrrolopyrrole-based fluorescence probes for the imaging of lysosomal Zn(2+) and identification of prostate cancer in human tissue
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title_fullStr | Diketopyrrolopyrrole-based fluorescence probes for the imaging of lysosomal Zn(2+) and identification of prostate cancer in human tissue
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title_full_unstemmed | Diketopyrrolopyrrole-based fluorescence probes for the imaging of lysosomal Zn(2+) and identification of prostate cancer in human tissue
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title_short | Diketopyrrolopyrrole-based fluorescence probes for the imaging of lysosomal Zn(2+) and identification of prostate cancer in human tissue
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title_sort | diketopyrrolopyrrole-based fluorescence probes for the imaging of lysosomal zn(2+) and identification of prostate cancer in human tissue |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6568042/ https://www.ncbi.nlm.nih.gov/pubmed/31293754 http://dx.doi.org/10.1039/c9sc01153f |
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