Use of Ruthenium Complexes as Photosensitizers in Photodynamic Therapy

Lilge, Lothar

doi:10.1002/9783527695225.ch6

Cited by 7 publications

(4 citation statements)

References 141 publications

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“…Based on their photophysical and electrochemical properties, Ru(II) complexes have been considered for light‐based applications and are under investigation as PSs for PDT . The wide range of different triplet excited states makes the Ru(II) complexes attractive for PDT.…”

Section: Introductionmentioning

confidence: 99%

Correlation of intracellular oxygen and cell metabolism by simultaneous PLIM of phosphorescent TLD1433 and FLIM of NAD(P)H

Kalinina

Breymayer

Reess

et al. 2018

Journal of Biophotonics

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During photodynamic therapy (PDT), disruption of cell respiration and metabolic changes could be one of the first events. Photophysical characteristics of the photosensitizer (PS) and its specific redox potential define consumption of molecular oxygen followed by generation of reactive oxygen species. The potential PS TLD1433 is based on transition metal Ru(II) and possess an oxygen-dependent luminescence. This enables the study of oxygen consumption by PS-phosphorescence lifetime imaging (PLIM) and simultaneously changes the cellular metabolic state by nicotinamide adenine dinucleotide (NAD(P)H)-fluorescence lifetime imaging (FLIM). Within this study, localization and cellular function of TLD1433 is investigated in bladder carcinoma cells using time-resolved and confocal laser scanning microscopy. Simultaneous FLIM/PLIM of NAD(P)H and TLD1433 during PDT correlated oxygen consumption, redox state and cellular energy metabolism. Our investigations aimed to provide a personalized protocol in theranostic PDT procedures and demonstrate the potential use of TLD1433 PDT also under hypoxic conditions, which are otherwise difficult to treat.

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Section: Introductionmentioning

confidence: 99%

Correlation of intracellular oxygen and cell metabolism by simultaneous PLIM of phosphorescent TLD1433 and FLIM of NAD(P)H

Kalinina

Breymayer

Reess

et al. 2018

Journal of Biophotonics

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“…Among non-porphyrin PSs, the use of ruthenium(II) (Ru(II)) polypyridyl complexes has recently received much interest thanks to their simple synthesis, chemical stability, good 1 O 2 production yields, and generally good aqueous solubility. − Notably, TLD-1433 is currently involved in a phase II clinical trial for patients with bladder cancer. , However, these Ru(II)-based PSs are known to poorly absorb light in the biological spectral window (600–900 nm). , This feature prevents the treatment of tumors located deeply in the tissues or of large tumors …”

Section: Introductionmentioning

confidence: 99%

In Situ Bioconjugation of a Maleimide-Functionalized Ruthenium-Based Photosensitizer to Albumin for Photodynamic Therapy

Vinck,

Dömötör,

Karges

et al. 2023

Inorg. Chem.

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Maleimide-containing prodrugs can quickly and selectively react with circulating serum albumin following their injection in the bloodstream. The drug–albumin complex then benefits from longer blood circulation times and better tumor accumulation. Herein, we have applied this strategy to a previously reported highly phototoxic Ru polypyridyl complex-based photosensitizer to increase its accumulation at the tumor, reduce off-target cytotoxicity, and therefore improve its pharmacological profile. Specifically, two complexes were synthesized bearing a maleimide group: one complex with the maleimide directly incorporated into the bipyridyl ligand, and the other has a hydrophilic linker between the ligand and the maleimide group. Their interaction with albumin was studied in-depth, revealing their ability to efficiently bind both covalently and noncovalently to the plasma protein. A crucial finding is that the maleimide-functionalized complexes exhibited significantly lower cytotoxicity in noncancerous cells under dark conditions compared to the nonfunctionalized complex, which is a highly desirable property for a photosensitizer. The binding to albumin also led to a decrease in the phototoxicity of the Ru bioconjugates in comparison to the nonfunctionalized complex, probably due to a decreased cellular uptake. Unfortunately, this decrease in phototoxicity was not compensated by a dramatic increase in tumor accumulation, as was demonstrated in a tumor-bearing mouse model using inductively coupled plasma mass spectrometry (ICP-MS) studies. Consequently, this study provides valuable insight into the future design of in situ albumin-binding complexes for photodynamic therapy in order to maximize their effectiveness and realize their full potential.

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“…While ideally the PS should not cause any cellular damage in the absence of light, it catalytically generates cytotoxic reactive oxygen species upon light irradiation. The latter ultimately triggers cell death. − Among the different types of PSs studied, the use of Ru(II) polypyridine complexes is receiving increasing attention. − Despite their attractive photophysical properties, the majority of these PSs are excited using blue or UV-A light. These wavelengths are poorly penetrating tissue, limiting the application of these compounds to superficial treatments. − Therefore, there is much research efforts invested toward the development of Ru(II) polypyridine complexes with an absorption in the biological spectral window (600–900 nm), which would provide a deeper tissue penetration. , In this context, we have recently reported the computational guided design of Ru(II) polypyridine complexes as PSs for longer wavelengths.…”

Section: Introductionmentioning

confidence: 99%

Polymeric Encapsulation of a Ru(II)-Based Photosensitizer for Folate-Targeted Photodynamic Therapy of Drug Resistant Cancers

2021

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The currently used photodynamic therapy (PDT) photosensitizers (PSs) are generally associated with a poor cancer cell selectivity, which is responsible for some undesirable side effects. To overcome these problems, there is an urgent need for a selective drug delivery system for PDT PSs. Herein, the encapsulation of a promising Ru(II) polypyridine complex in a polymer with terminal folate groups to form nanoparticles is presented. While the Ru(II) complex itself has a cytotoxic effect in the dark, the encapsulation is able to overcome this drawback. Upon light exposure, the nanoparticles were found to be highly phototoxic in 2D monolayer cells as well as 3D multicellular tumor spheroids upon 480 or 595 nm irradiation. Importantly, the nanoparticles demonstrated a high selectivity for cancerous cells over noncancerous cells and were found to be active in drug resistant cancer cells lines, indicating that they are able to overcome drug resistances.

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Use of Ruthenium Complexes as Photosensitizers in Photodynamic Therapy

Cited by 7 publications

References 141 publications

Correlation of intracellular oxygen and cell metabolism by simultaneous PLIM of phosphorescent TLD1433 and FLIM of NAD(P)H

Correlation of intracellular oxygen and cell metabolism by simultaneous PLIM of phosphorescent TLD1433 and FLIM of NAD(P)H

In Situ Bioconjugation of a Maleimide-Functionalized Ruthenium-Based Photosensitizer to Albumin for Photodynamic Therapy

Polymeric Encapsulation of a Ru(II)-Based Photosensitizer for Folate-Targeted Photodynamic Therapy of Drug Resistant Cancers

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