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Monitoring mitochondrial viscosity with anticancer phosphorescent Ir(iii) complexes via two-photon lifetime imaging
Precise quantitative measurement of viscosity at the subcellular level presents great challenges. Two-photon phosphorescence lifetime imaging microscopy (TPPLIM) can reflect micro-environmental changes of a chromophore in a quantitative manner. Phosphorescent iridium complexes are potential TPPLIM p...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Royal Society of Chemistry
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357858/ https://www.ncbi.nlm.nih.gov/pubmed/30809342 http://dx.doi.org/10.1039/c8sc04242j |
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author | Hao, Liang Li, Zhi-Wei Zhang, Dong-Yang He, Liang Liu, Wenting Yang, Jing Tan, Cai-Ping Ji, Liang-Nian Mao, Zong-Wan |
author_facet | Hao, Liang Li, Zhi-Wei Zhang, Dong-Yang He, Liang Liu, Wenting Yang, Jing Tan, Cai-Ping Ji, Liang-Nian Mao, Zong-Wan |
author_sort | Hao, Liang |
collection | PubMed |
description | Precise quantitative measurement of viscosity at the subcellular level presents great challenges. Two-photon phosphorescence lifetime imaging microscopy (TPPLIM) can reflect micro-environmental changes of a chromophore in a quantitative manner. Phosphorescent iridium complexes are potential TPPLIM probes due to their rich photophysical properties including environment-sensitive long-lifetime emission and high two-photon absorption (TPA) properties. In this work, a series of iridium(iii) complexes containing rotatable groups are developed as mitochondria-targeting anticancer agents and quantitative viscosity probes. Among them, Ir6 ([Ir(ppy-CHO)(2)(dppe)]PF(6); ppy-CHO: 4-(2-pyridyl)benzaldehyde; dppe: cis-1,2-bis(diphenylphosphino)ethene) shows satisfactory TPA properties and long lifetimes (up to 1 μs). The emission intensities and lifetimes of Ir6 are viscosity-dependent, which is mainly attributed to the configurational changes in the diphosphine ligand as proved by (1)H NMR spectra. Ir6 displays potent cytotoxicity, and mechanism investigations show that it can accumulate in mitochondria and induce apoptotic cell death. Moreover, Ir6 can induce mitochondrial dysfunction and monitor the changes in mitochondrial viscosity simultaneously in a real-time and quantitative manner via TPPLIM. Upon Ir6 treatment, a time-dependent increase in viscosity and heterogeneity is observed along with the loss of membrane potential in mitochondria. In summary, our work shows that multifunctional phosphorescent metal complexes can induce and precisely detect microenvironmental changes simultaneously at the subcellular level using TPPLIM, which may deepen the understanding of the cell death mechanisms induced by these metallocompounds. |
format | Online Article Text |
id | pubmed-6357858 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-63578582019-02-26 Monitoring mitochondrial viscosity with anticancer phosphorescent Ir(iii) complexes via two-photon lifetime imaging Hao, Liang Li, Zhi-Wei Zhang, Dong-Yang He, Liang Liu, Wenting Yang, Jing Tan, Cai-Ping Ji, Liang-Nian Mao, Zong-Wan Chem Sci Chemistry Precise quantitative measurement of viscosity at the subcellular level presents great challenges. Two-photon phosphorescence lifetime imaging microscopy (TPPLIM) can reflect micro-environmental changes of a chromophore in a quantitative manner. Phosphorescent iridium complexes are potential TPPLIM probes due to their rich photophysical properties including environment-sensitive long-lifetime emission and high two-photon absorption (TPA) properties. In this work, a series of iridium(iii) complexes containing rotatable groups are developed as mitochondria-targeting anticancer agents and quantitative viscosity probes. Among them, Ir6 ([Ir(ppy-CHO)(2)(dppe)]PF(6); ppy-CHO: 4-(2-pyridyl)benzaldehyde; dppe: cis-1,2-bis(diphenylphosphino)ethene) shows satisfactory TPA properties and long lifetimes (up to 1 μs). The emission intensities and lifetimes of Ir6 are viscosity-dependent, which is mainly attributed to the configurational changes in the diphosphine ligand as proved by (1)H NMR spectra. Ir6 displays potent cytotoxicity, and mechanism investigations show that it can accumulate in mitochondria and induce apoptotic cell death. Moreover, Ir6 can induce mitochondrial dysfunction and monitor the changes in mitochondrial viscosity simultaneously in a real-time and quantitative manner via TPPLIM. Upon Ir6 treatment, a time-dependent increase in viscosity and heterogeneity is observed along with the loss of membrane potential in mitochondria. In summary, our work shows that multifunctional phosphorescent metal complexes can induce and precisely detect microenvironmental changes simultaneously at the subcellular level using TPPLIM, which may deepen the understanding of the cell death mechanisms induced by these metallocompounds. Royal Society of Chemistry 2018-12-04 /pmc/articles/PMC6357858/ /pubmed/30809342 http://dx.doi.org/10.1039/c8sc04242j Text en This journal is © The Royal Society of Chemistry 2019 https://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 Hao, Liang Li, Zhi-Wei Zhang, Dong-Yang He, Liang Liu, Wenting Yang, Jing Tan, Cai-Ping Ji, Liang-Nian Mao, Zong-Wan Monitoring mitochondrial viscosity with anticancer phosphorescent Ir(iii) complexes via two-photon lifetime imaging |
title | Monitoring mitochondrial viscosity with anticancer phosphorescent Ir(iii) complexes via two-photon lifetime imaging
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title_full | Monitoring mitochondrial viscosity with anticancer phosphorescent Ir(iii) complexes via two-photon lifetime imaging
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title_fullStr | Monitoring mitochondrial viscosity with anticancer phosphorescent Ir(iii) complexes via two-photon lifetime imaging
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title_full_unstemmed | Monitoring mitochondrial viscosity with anticancer phosphorescent Ir(iii) complexes via two-photon lifetime imaging
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title_short | Monitoring mitochondrial viscosity with anticancer phosphorescent Ir(iii) complexes via two-photon lifetime imaging
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title_sort | monitoring mitochondrial viscosity with anticancer phosphorescent ir(iii) complexes via two-photon lifetime imaging |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357858/ https://www.ncbi.nlm.nih.gov/pubmed/30809342 http://dx.doi.org/10.1039/c8sc04242j |
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