Metal Complexes for Two-Photon Photodynamic Therapy: A Cyclometallated Iridium Complex Induces Two-Photon Photosensitization of Cancer Cells under Near-IR Light

Luke K. McKenzie; Igor V. Sazanovich; Elizabeth Baggaley; Mickaële Bonneau; Véronique Guerchais; J. A.Gareth Williams; Julia A. Weinstein; Helen E. Bryant

doi:10.1002/chem.201604792

Metal Complexes for Two-Photon Photodynamic Therapy: A Cyclometallated Iridium Complex Induces Two-Photon Photosensitization of Cancer Cells under Near-IR Light

Luke K. McKenzie, Igor V. Sazanovich, Elizabeth Baggaley, Mickaële Bonneau, Véronique Guerchais, J. A.Gareth Williams, Julia A. Weinstein^*, Helen E. Bryant

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

148 Scopus citations

Abstract

Photodynamic therapy (PDT) uses photosensitizers (PS) which only become cytotoxic upon light-irradiation. Transition-metal complexes are highly promising PS due to long excited-state lifetimes, and high photo-stabilities. However, these complexes usually absorb higher-energy UV/Vis light, whereas the optimal tissue transparency is in the lower-energy NIR region. Two-photon excitation (TPE) can overcome this dichotomy, with simultaneous absorption of two lower-energy NIR-photons populating the same PS-active excited state as one higher-energy photon. We introduce two low-molecular weight, long-lived and photo-stable iridium complexes of the [Ir(N^C)₂(N^N)]⁺ family with high TP-absorption, which localise to mitochondria and lysosomal structures in live cells. The compounds are efficient PS under 1-photon irradiation (405 nm) resulting in apoptotic cell death in diverse cancer cell lines at low light doses (3.6 J cm⁻²), low concentrations, and photo-indexes greater than 555. Remarkably 1 also displays high PS activity killing cancer cells under NIR two-photon excitation (760 nm), which along with its photo-stability indicates potential future clinical application.

Original language	English (US)
Pages (from-to)	234-238
Number of pages	5
Journal	Chemistry - A European Journal
Volume	23
Issue number	2
DOIs	https://doi.org/10.1002/chem.201604792
State	Published - Jan 5 2017

Bibliographical note

Funding Information:
This work was funded jointly by Yorkshire Cancer Research, Cancer Research UK, BBSRC, EPSRC KTA and MRC POC funds, University of Durham and CNRS (France). Microscopy was performed on equipment purchased by Welcome Trust grant WT093134AIA and MRC SHIMA award MR/K015753/1. The authors would like to thank Prof. Botchway, Dr. Grey, Mr. Shewring and Dr. Delor for help and advice, and Dr. Robinson for help in capturing images.

Publisher Copyright:
© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Keywords

cancer therapy
iridium
singlet oxygen
transition metals
two-photon photodynamic therapy

ASJC Scopus subject areas

Catalysis
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/chem.201604792

Cite this

McKenzie, L. K., Sazanovich, I. V., Baggaley, E., Bonneau, M., Guerchais, V., Williams, J. A. G., Weinstein, J. A., & Bryant, H. E. (2017). Metal Complexes for Two-Photon Photodynamic Therapy: A Cyclometallated Iridium Complex Induces Two-Photon Photosensitization of Cancer Cells under Near-IR Light. Chemistry - A European Journal, 23(2), 234-238. https://doi.org/10.1002/chem.201604792

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title = "Metal Complexes for Two-Photon Photodynamic Therapy: A Cyclometallated Iridium Complex Induces Two-Photon Photosensitization of Cancer Cells under Near-IR Light",

abstract = "Photodynamic therapy (PDT) uses photosensitizers (PS) which only become cytotoxic upon light-irradiation. Transition-metal complexes are highly promising PS due to long excited-state lifetimes, and high photo-stabilities. However, these complexes usually absorb higher-energy UV/Vis light, whereas the optimal tissue transparency is in the lower-energy NIR region. Two-photon excitation (TPE) can overcome this dichotomy, with simultaneous absorption of two lower-energy NIR-photons populating the same PS-active excited state as one higher-energy photon. We introduce two low-molecular weight, long-lived and photo-stable iridium complexes of the [Ir(N^C)2(N^N)]+ family with high TP-absorption, which localise to mitochondria and lysosomal structures in live cells. The compounds are efficient PS under 1-photon irradiation (405 nm) resulting in apoptotic cell death in diverse cancer cell lines at low light doses (3.6 J cm−2), low concentrations, and photo-indexes greater than 555. Remarkably 1 also displays high PS activity killing cancer cells under NIR two-photon excitation (760 nm), which along with its photo-stability indicates potential future clinical application.",

keywords = "cancer therapy, iridium, singlet oxygen, transition metals, two-photon photodynamic therapy",

author = "McKenzie, {Luke K.} and Sazanovich, {Igor V.} and Elizabeth Baggaley and Micka{\"e}le Bonneau and V{\'e}ronique Guerchais and Williams, {J. A.Gareth} and Weinstein, {Julia A.} and Bryant, {Helen E.}",

note = "Funding Information: This work was funded jointly by Yorkshire Cancer Research, Cancer Research UK, BBSRC, EPSRC KTA and MRC POC funds, University of Durham and CNRS (France). Microscopy was performed on equipment purchased by Welcome Trust grant WT093134AIA and MRC SHIMA award MR/K015753/1. The authors would like to thank Prof. Botchway, Dr. Grey, Mr. Shewring and Dr. Delor for help and advice, and Dr. Robinson for help in capturing images. Publisher Copyright: {\textcopyright} 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.",

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McKenzie, LK, Sazanovich, IV, Baggaley, E, Bonneau, M, Guerchais, V, Williams, JAG, Weinstein, JA & Bryant, HE 2017, 'Metal Complexes for Two-Photon Photodynamic Therapy: A Cyclometallated Iridium Complex Induces Two-Photon Photosensitization of Cancer Cells under Near-IR Light', Chemistry - A European Journal, vol. 23, no. 2, pp. 234-238. https://doi.org/10.1002/chem.201604792

Metal Complexes for Two-Photon Photodynamic Therapy: A Cyclometallated Iridium Complex Induces Two-Photon Photosensitization of Cancer Cells under Near-IR Light. / McKenzie, Luke K.; Sazanovich, Igor V.; Baggaley, Elizabeth et al.
In: Chemistry - A European Journal, Vol. 23, No. 2, 05.01.2017, p. 234-238.

Research output: Contribution to journal › Article › peer-review

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T1 - Metal Complexes for Two-Photon Photodynamic Therapy

T2 - A Cyclometallated Iridium Complex Induces Two-Photon Photosensitization of Cancer Cells under Near-IR Light

AU - McKenzie, Luke K.

AU - Sazanovich, Igor V.

AU - Baggaley, Elizabeth

AU - Bonneau, Mickaële

AU - Guerchais, Véronique

AU - Williams, J. A.Gareth

AU - Weinstein, Julia A.

AU - Bryant, Helen E.

N1 - Funding Information: This work was funded jointly by Yorkshire Cancer Research, Cancer Research UK, BBSRC, EPSRC KTA and MRC POC funds, University of Durham and CNRS (France). Microscopy was performed on equipment purchased by Welcome Trust grant WT093134AIA and MRC SHIMA award MR/K015753/1. The authors would like to thank Prof. Botchway, Dr. Grey, Mr. Shewring and Dr. Delor for help and advice, and Dr. Robinson for help in capturing images. Publisher Copyright: © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

PY - 2017/1/5

Y1 - 2017/1/5

N2 - Photodynamic therapy (PDT) uses photosensitizers (PS) which only become cytotoxic upon light-irradiation. Transition-metal complexes are highly promising PS due to long excited-state lifetimes, and high photo-stabilities. However, these complexes usually absorb higher-energy UV/Vis light, whereas the optimal tissue transparency is in the lower-energy NIR region. Two-photon excitation (TPE) can overcome this dichotomy, with simultaneous absorption of two lower-energy NIR-photons populating the same PS-active excited state as one higher-energy photon. We introduce two low-molecular weight, long-lived and photo-stable iridium complexes of the [Ir(N^C)2(N^N)]+ family with high TP-absorption, which localise to mitochondria and lysosomal structures in live cells. The compounds are efficient PS under 1-photon irradiation (405 nm) resulting in apoptotic cell death in diverse cancer cell lines at low light doses (3.6 J cm−2), low concentrations, and photo-indexes greater than 555. Remarkably 1 also displays high PS activity killing cancer cells under NIR two-photon excitation (760 nm), which along with its photo-stability indicates potential future clinical application.

AB - Photodynamic therapy (PDT) uses photosensitizers (PS) which only become cytotoxic upon light-irradiation. Transition-metal complexes are highly promising PS due to long excited-state lifetimes, and high photo-stabilities. However, these complexes usually absorb higher-energy UV/Vis light, whereas the optimal tissue transparency is in the lower-energy NIR region. Two-photon excitation (TPE) can overcome this dichotomy, with simultaneous absorption of two lower-energy NIR-photons populating the same PS-active excited state as one higher-energy photon. We introduce two low-molecular weight, long-lived and photo-stable iridium complexes of the [Ir(N^C)2(N^N)]+ family with high TP-absorption, which localise to mitochondria and lysosomal structures in live cells. The compounds are efficient PS under 1-photon irradiation (405 nm) resulting in apoptotic cell death in diverse cancer cell lines at low light doses (3.6 J cm−2), low concentrations, and photo-indexes greater than 555. Remarkably 1 also displays high PS activity killing cancer cells under NIR two-photon excitation (760 nm), which along with its photo-stability indicates potential future clinical application.

KW - cancer therapy

KW - iridium

KW - singlet oxygen

KW - transition metals

KW - two-photon photodynamic therapy

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DO - 10.1002/chem.201604792

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Metal Complexes for Two-Photon Photodynamic Therapy: A Cyclometallated Iridium Complex Induces Two-Photon Photosensitization of Cancer Cells under Near-IR Light

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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