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A library of Rhodamine6G-based pH-sensitive fluorescent probes with versatile in vivo and in vitro applications

Acidic pH is critical to the function of the gastrointestinal system, bone-resorbing osteoclasts, and the endolysosomal compartment of nearly every cell in the body. Non-invasive, real-time fluorescence imaging of acidic microenvironments represents a powerful tool for understanding normal cellular...

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Autores principales: Swanson, W. Benton, Durdan, Margaret, Eberle, Miranda, Woodbury, Seth, Mauser, Ava, Gregory, Jason, Zhang, Boya, Niemann, David, Herremans, Jacob, Ma, Peter X., Lahann, Joerg, Weivoda, Megan, Mishina, Yuji, Greineder, Colin F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: RSC 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175114/
https://www.ncbi.nlm.nih.gov/pubmed/35755193
http://dx.doi.org/10.1039/d2cb00030j
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author Swanson, W. Benton
Durdan, Margaret
Eberle, Miranda
Woodbury, Seth
Mauser, Ava
Gregory, Jason
Zhang, Boya
Niemann, David
Herremans, Jacob
Ma, Peter X.
Lahann, Joerg
Weivoda, Megan
Mishina, Yuji
Greineder, Colin F.
author_facet Swanson, W. Benton
Durdan, Margaret
Eberle, Miranda
Woodbury, Seth
Mauser, Ava
Gregory, Jason
Zhang, Boya
Niemann, David
Herremans, Jacob
Ma, Peter X.
Lahann, Joerg
Weivoda, Megan
Mishina, Yuji
Greineder, Colin F.
author_sort Swanson, W. Benton
collection PubMed
description Acidic pH is critical to the function of the gastrointestinal system, bone-resorbing osteoclasts, and the endolysosomal compartment of nearly every cell in the body. Non-invasive, real-time fluorescence imaging of acidic microenvironments represents a powerful tool for understanding normal cellular biology, defining mechanisms of disease, and monitoring for therapeutic response. While commercially available pH-sensitive fluorescent probes exist, several limitations hinder their widespread use and potential for biologic application. To address this need, we developed a novel library of pH-sensitive probes based on the highly photostable and water-soluble fluorescent molecule, Rhodamine 6G. We demonstrate versatility in terms of both pH sensitivity (i.e., pK(a)) and chemical functionality, allowing conjugation to small molecules, proteins, nanoparticles, and regenerative biomaterial scaffold matrices. Furthermore, we show preserved pH-sensitive fluorescence following a variety of forms of covalent functionalization and demonstrate three potential applications, both in vitro and in vivo, for intracellular and extracellular pH sensing. Finally, we develop a computation approach for predicting the pH sensitivity of R6G derivatives, which could be used to expand our library and generate probes with novel properties.
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spelling pubmed-91751142022-06-23 A library of Rhodamine6G-based pH-sensitive fluorescent probes with versatile in vivo and in vitro applications Swanson, W. Benton Durdan, Margaret Eberle, Miranda Woodbury, Seth Mauser, Ava Gregory, Jason Zhang, Boya Niemann, David Herremans, Jacob Ma, Peter X. Lahann, Joerg Weivoda, Megan Mishina, Yuji Greineder, Colin F. RSC Chem Biol Chemistry Acidic pH is critical to the function of the gastrointestinal system, bone-resorbing osteoclasts, and the endolysosomal compartment of nearly every cell in the body. Non-invasive, real-time fluorescence imaging of acidic microenvironments represents a powerful tool for understanding normal cellular biology, defining mechanisms of disease, and monitoring for therapeutic response. While commercially available pH-sensitive fluorescent probes exist, several limitations hinder their widespread use and potential for biologic application. To address this need, we developed a novel library of pH-sensitive probes based on the highly photostable and water-soluble fluorescent molecule, Rhodamine 6G. We demonstrate versatility in terms of both pH sensitivity (i.e., pK(a)) and chemical functionality, allowing conjugation to small molecules, proteins, nanoparticles, and regenerative biomaterial scaffold matrices. Furthermore, we show preserved pH-sensitive fluorescence following a variety of forms of covalent functionalization and demonstrate three potential applications, both in vitro and in vivo, for intracellular and extracellular pH sensing. Finally, we develop a computation approach for predicting the pH sensitivity of R6G derivatives, which could be used to expand our library and generate probes with novel properties. RSC 2022-04-29 /pmc/articles/PMC9175114/ /pubmed/35755193 http://dx.doi.org/10.1039/d2cb00030j Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Swanson, W. Benton
Durdan, Margaret
Eberle, Miranda
Woodbury, Seth
Mauser, Ava
Gregory, Jason
Zhang, Boya
Niemann, David
Herremans, Jacob
Ma, Peter X.
Lahann, Joerg
Weivoda, Megan
Mishina, Yuji
Greineder, Colin F.
A library of Rhodamine6G-based pH-sensitive fluorescent probes with versatile in vivo and in vitro applications
title A library of Rhodamine6G-based pH-sensitive fluorescent probes with versatile in vivo and in vitro applications
title_full A library of Rhodamine6G-based pH-sensitive fluorescent probes with versatile in vivo and in vitro applications
title_fullStr A library of Rhodamine6G-based pH-sensitive fluorescent probes with versatile in vivo and in vitro applications
title_full_unstemmed A library of Rhodamine6G-based pH-sensitive fluorescent probes with versatile in vivo and in vitro applications
title_short A library of Rhodamine6G-based pH-sensitive fluorescent probes with versatile in vivo and in vitro applications
title_sort library of rhodamine6g-based ph-sensitive fluorescent probes with versatile in vivo and in vitro applications
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175114/
https://www.ncbi.nlm.nih.gov/pubmed/35755193
http://dx.doi.org/10.1039/d2cb00030j
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