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.

Valproic Acid‐Functionalized Cyclometalated Iridium(III) Complexes as Mitochondria‐Targeting Anticancer Agents

“…Over the measured range, the maximum TPA cross sections δ max of 1 a – 3 a and 1 b – 3 b ranged from 38 to 129 GM (1 GM=10 −50 cm 4 photon −1 ) at λ =740 nm (Figure S14 and Table S3 of the Supporting Information). These values are moderate compared with those of other Ir III complexes measured by the same method ,. From the log–log plot of the emission intensity against incident power, the linear regression slopes of 1 a – 3 a and 1 b – 3 b are 1.98±0.01, 2.00±0.03, 2.05±0.01, 1.95±0.02, 2.05±0.01 and 1.94±0.01, respectively, which indicate nonlinear TPA of the Ir III complexes (Figure S15 of the Supporting Information).…”

Preise der Royal Society of Chemistry für 2017

“…Sie interessiert sich für die lichtinduzierte Ladungstrennung in nanoskaligen molekularen Systemen, ultraschnelle elektronische und Strukturdynamiken, die Schwingungssteuerung lichtinduzierter Reaktionen sowie die Entwicklung der zeitaufgelösten bildgebenden Emissionsmikroskopie in den Biowissenschaften. In Chemistry—A European Journal hat sie über Metallkomplexe für die photodynamische Zweiphotonentherapie berichtet …”

Photocytotoxic Copper(II) Complexes with Schiff‐Base Scaffolds for Photodynamic Therapy

“…[1][2][3][4] For this purpose, several photosensitizers, such as Photofrin, 5-aminolevulinic acid (ALA), Foscan, and Verteporn, have been clinically approved for the treatment of cancersa nd skin diseases with light irradiation. [1][2][3][4] For this purpose, several photosensitizers, such as Photofrin, 5-aminolevulinic acid (ALA), Foscan, and Verteporn, have been clinically approved for the treatment of cancersa nd skin diseases with light irradiation.…”

“…Due to the lowers ide effects of photodynamic therapy( PDT) as compared to chemo-and radiotherapies, it has been effectively applied in the development of therapeutic cancert reatment. [1][2][3][4] For this purpose, several photosensitizers, such as Photofrin, 5-aminolevulinic acid (ALA), Foscan, and Verteporn, have been clinically approved for the treatment of cancersa nd skin diseases with light irradiation. [5,6] Recently,t oi mprove the selectivity and efficacy against canceri nP DT treatments, transition metal complexes have been considered.…”