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A side-chain engineering strategy for constructing fluorescent dyes with direct and ultrafast self-delivery to living cells

Organic fluorescent dyes with excellent self-delivery to living cells are always difficult to find due to the limitation of the plasma membrane having rigorous selectivity. Herein, in order to improve the permeability of dyes, we utilize a side-chain engineering strategy (SCES): adjusting the side-c...

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Autores principales: Guo, Lifang, Li, Chuanya, Shang, Hai, Zhang, Ruoyao, Li, Xuechen, Lu, Qing, Cheng, Xiao, Liu, Zhiqiang, Sun, Jing Zhi, Yu, Xiaoqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145637/
https://www.ncbi.nlm.nih.gov/pubmed/34123038
http://dx.doi.org/10.1039/c9sc05875c
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author Guo, Lifang
Li, Chuanya
Shang, Hai
Zhang, Ruoyao
Li, Xuechen
Lu, Qing
Cheng, Xiao
Liu, Zhiqiang
Sun, Jing Zhi
Yu, Xiaoqiang
author_facet Guo, Lifang
Li, Chuanya
Shang, Hai
Zhang, Ruoyao
Li, Xuechen
Lu, Qing
Cheng, Xiao
Liu, Zhiqiang
Sun, Jing Zhi
Yu, Xiaoqiang
author_sort Guo, Lifang
collection PubMed
description Organic fluorescent dyes with excellent self-delivery to living cells are always difficult to find due to the limitation of the plasma membrane having rigorous selectivity. Herein, in order to improve the permeability of dyes, we utilize a side-chain engineering strategy (SCES): adjusting the side-chain length of dyes to fine-tune the adsorption and desorption processes on the membrane–aqueous phase interfaces of the outer and inner leaflets of the plasma membrane. For this, a family of fluorescent derivatives (SPs) was prepared by functionalizing a styryl-pyridinium fluorophore with alkyl side-chains containing a different carbon number from 1 to 22. Systematic experimental investigations and simulated calculations demonstrate that the self-delivery rate of SPs with a suitable length side-chain is about 22-fold higher in SiHa cells and 76-fold higher in mesenchymal stem cells than that of unmodified SP-1, enabling cell-imaging at an ultralow loading concentration of 1 nM and deep penetration in turbid tissue and in vivo. Moreover, the SCES can even endow a membrane-impermeable fluorescent scaffold with good permeability. Further, quantitative research on the relationship between Clog P and cell permeability shows that when Clog P is in the range of 1.3–2.5, dyes possess optimal permeability. Therefore, this work not only systematically reports the effect of side-chain length on dye delivery for the first time, but also provides some ideal fluorescent probes. At the same time, it gives a suitable Clog P range for efficient cellular delivery, which can serve as a guide for designing cell-permeant dyes. In a word, all the results reveal that the SCES is an effective strategy to dramatically improve dye permeability.
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spelling pubmed-81456372021-06-11 A side-chain engineering strategy for constructing fluorescent dyes with direct and ultrafast self-delivery to living cells Guo, Lifang Li, Chuanya Shang, Hai Zhang, Ruoyao Li, Xuechen Lu, Qing Cheng, Xiao Liu, Zhiqiang Sun, Jing Zhi Yu, Xiaoqiang Chem Sci Chemistry Organic fluorescent dyes with excellent self-delivery to living cells are always difficult to find due to the limitation of the plasma membrane having rigorous selectivity. Herein, in order to improve the permeability of dyes, we utilize a side-chain engineering strategy (SCES): adjusting the side-chain length of dyes to fine-tune the adsorption and desorption processes on the membrane–aqueous phase interfaces of the outer and inner leaflets of the plasma membrane. For this, a family of fluorescent derivatives (SPs) was prepared by functionalizing a styryl-pyridinium fluorophore with alkyl side-chains containing a different carbon number from 1 to 22. Systematic experimental investigations and simulated calculations demonstrate that the self-delivery rate of SPs with a suitable length side-chain is about 22-fold higher in SiHa cells and 76-fold higher in mesenchymal stem cells than that of unmodified SP-1, enabling cell-imaging at an ultralow loading concentration of 1 nM and deep penetration in turbid tissue and in vivo. Moreover, the SCES can even endow a membrane-impermeable fluorescent scaffold with good permeability. Further, quantitative research on the relationship between Clog P and cell permeability shows that when Clog P is in the range of 1.3–2.5, dyes possess optimal permeability. Therefore, this work not only systematically reports the effect of side-chain length on dye delivery for the first time, but also provides some ideal fluorescent probes. At the same time, it gives a suitable Clog P range for efficient cellular delivery, which can serve as a guide for designing cell-permeant dyes. In a word, all the results reveal that the SCES is an effective strategy to dramatically improve dye permeability. The Royal Society of Chemistry 2019-12-04 /pmc/articles/PMC8145637/ /pubmed/34123038 http://dx.doi.org/10.1039/c9sc05875c Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Guo, Lifang
Li, Chuanya
Shang, Hai
Zhang, Ruoyao
Li, Xuechen
Lu, Qing
Cheng, Xiao
Liu, Zhiqiang
Sun, Jing Zhi
Yu, Xiaoqiang
A side-chain engineering strategy for constructing fluorescent dyes with direct and ultrafast self-delivery to living cells
title A side-chain engineering strategy for constructing fluorescent dyes with direct and ultrafast self-delivery to living cells
title_full A side-chain engineering strategy for constructing fluorescent dyes with direct and ultrafast self-delivery to living cells
title_fullStr A side-chain engineering strategy for constructing fluorescent dyes with direct and ultrafast self-delivery to living cells
title_full_unstemmed A side-chain engineering strategy for constructing fluorescent dyes with direct and ultrafast self-delivery to living cells
title_short A side-chain engineering strategy for constructing fluorescent dyes with direct and ultrafast self-delivery to living cells
title_sort side-chain engineering strategy for constructing fluorescent dyes with direct and ultrafast self-delivery to living cells
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145637/
https://www.ncbi.nlm.nih.gov/pubmed/34123038
http://dx.doi.org/10.1039/c9sc05875c
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