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,Véronique Guerchais,Mickaële Bonneau,J A Gareth Williams,Elizabeth Baggaley,Helen E Bryant,Julia A Weinstein

doi:10.1002/chem.201604792

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.

Highlights

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. These complexes usually absorb higherenergy UV/Vis light, whereas the optimal tissue transparency is in the lower-energy NIR region
In oxygen-dependent PDT, cellular oxygen and *PS interactions allow excited-state energy transfer, regenerating the ground state of the PS and producing reactive oxygen species (ROS) including singlet oxygen (1O2), with subsequent reactions with the intracellular components leading to cell death

Summary

Introduction

Photodynamic therapy (PDT) uses photosensitizers (PS) which only become cytotoxic upon light-irradiation. 1 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. We present two low-molecular-weight, mitochondrial and lysosomal targeting, iridium complexes which display good PS activity under one-photon excitation in a number of cancer cell lines.

Results

Conclusion