TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=84996490642&partnerID=8YFLogxK
U2 - 10.1002/chem.201604792
DO - 10.1002/chem.201604792
M3 - Article
C2 - 27740703
AN - SCOPUS:84996490642
SN - 0947-6539
VL - 23
SP - 234
EP - 238
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 2
ER -
