Ru(II) containing photosensitizers for photodynamic therapy: A critique on reporting and an attempt to compare efficacy

Munegowda, Manjunatha Ankathatti; Manalac, Angelica; Weersink, Madrigal; McFarland, Sherri A.; Lilge, Lothar

doi:10.1016/j.ccr.2022.214712

Cited by 40 publications

(33 citation statements)

References 150 publications

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“…The phototherapy indexes under 450 (PI-1) and 808 nm (PI-2) for Ru1 reached as high as >275 and > 390, respectively, indicating that it is an IR-excitable PS for antitumor PDT. Both PI-1 and PI-2 of HPRCs are significantly high among metal-containing PSs summarized in recent reviews (typically <100). ,,,− The phototoxicity of HPRCs [Ru(dppz-X 2 ) 3 ] 2+ have been reported to decrease as their lipophilicity increases . Quite the contrary, for HPRCs in this work, a decrease in lipophilicity leads to an apparent reduction in phototoxicity.…”

Section: Resultsmentioning

confidence: 53%

More-Is-Better Strategy for Constructing Homoligand Polypyridyl Ruthenium Complexes as Photosensitizers for Infrared Two-Photon Photodynamic Therapy

Tang,

Wang,

Yang

et al. 2023

Inorg. Chem.

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Photodynamic therapy (PDT) uses a combination of photosensitizers (PSs), light sources, and reactive oxygen species (ROS) to damage only the desired target and keep normal tissues from being hurt. The dark cytotoxicity (chemotoxicity) of PSs, leading to whole-body damage in the absence of irradiation, is a major limiting factor in PDT. How to simultaneously increase ROS generation and decrease dark cytotoxicity is an essential challenge that must be resolved in PS research. In this study, a series of homoligand polypyridyl ruthenium complexes (HPRCs) containing three singlet oxygen ( 1 O 2 )-generating ligands (L) in a single molecule ([Ru(L) 3 ] 2+ ) have been constructed. Compared to the heteroligand complexes [Ru(bpy) 2 (L)] 2+ where bpy is 2,2′-bipyridine, the 1 O 2 quantum yield under infrared two-photon irradiation and the DNA photocleavage effect of the HPRCs are significantly enhanced with two more ligands L. The intraligand triplet excited states transition played an important role in the activation of oxygen. The HPRCs target the mitochondria but not the nuclei, generating 1 O 2 intracellularly under irradiation of visible or infrared light. Ru1 exhibits high phototoxicity and low dark cytotoxicity toward human malignant melanoma cells in vitro. Moreover, HPRCs have minimal cytotoxicity to human normal liver cells, suggesting their potential as antitumor PDT reagents with more security. This study may provide inspiration for the structural design of potent PS for PDT.

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Section: Resultsmentioning

confidence: 53%

More-Is-Better Strategy for Constructing Homoligand Polypyridyl Ruthenium Complexes as Photosensitizers for Infrared Two-Photon Photodynamic Therapy

Tang,

Wang,

Yang

et al. 2023

Inorg. Chem.

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Section: Photodynamic Therapymentioning

confidence: 99%

“…In addition to these attractive photophysical properties, the synthetic versatility accounting for the tunable excitation and emission wavelengths dramatically enriches their fine-tuning potential for desired properties. Excellent reviews focused on the progress of metal-based PSs have been respectively published by McFarland, [13,14] Gasser, [15] Weinstein, [16] and Turro. [17] Metal-based PSs have entered clinical trials or been approved for cancer therapies, to date, including Rostaporfin (Purlytin○R, for breast cancer and Kaposi's sarcoma treatment, under the phase II clinical trial), Motexafin Lutetium (Lutrin○Ror Antrin○R, for prostate cancer treatment, under the phase II clinical trial), Sulfonated Aluminum Phthalocyanine (Photosens○R, for lung, liver, breast, skin and gastrointestinal cancer treatment, has been clinically approved by Russia), Padeliporfin/WST09 (TOOKAD○R, for recurrent prostate cancer, under phase II clinical trial), derivative Padeliporfin/WST11 (TOOKAD○R soluble, has been clinically approved in more than 33 countries), and TDL1433 (for nonmuscle invasive bladder cancer treatment, under phase II clinical trial), giving new hope to myriad patients.…”

Section: Introductionmentioning

confidence: 99%

Recent Progress in Photodynamic Immunotherapy with Metal‐Based Photosensitizers

et al. 2022

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Cancer ranks as a leading cause of death. There is an urgent need to develop minimally invasive methods to eradicate tumors and prevent their recurrence. As a light‐driven modality, photodynamic therapy takes advantage of high tumor selectivity and low normal tissue damage. However, it shows poor potential for preventing tumor recurrence. Immunotherapy is currently being used as an alternative treatment for the control of malignant diseases. Although immunotherapy can establish long‐time immune memory and efficiently protects treated patients from cancer relapse, its clinical efficacy is limited by the minority of patients’ responding rate. Recently, photodynamic immunotherapy, which utilizes photosensitizers as an immunotherapy trigger to exert synergistic effects of photodynamic therapy and tumor immunotherapy, has attracted considerable interest. Like all the newly proposed treatments, there is still room for improvement. In this mini review, the progress in photodynamic immunotherapy with metal‐based photosensitizers is summarized. It is hoped that this review can give a broad update on photodynamic immunotherapy and inspire readers.

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“…To circumvent this drawback, PSs with absorption within the phototherapy window (600–900 nm) need to be developed, which can be achieved by the red-shifted OPA or upconverted TPA process. However, some studies have shown that a number of Ru(II) complexes also have a relatively weak δ value, which also limits their practical application in this area. , In addition, the triplet state lifetime is still insufficient to achieve the maximum intermolecular energy transfer or electron transfer efficiency. , …”

Section: Introductionmentioning

confidence: 99%

“…22,23 In addition, the triplet state lifetime is still insufficient to achieve the maximum intermolecular energy transfer or electron transfer efficiency. 24,25 For the above reasons, many researchers are working to design and synthesize pure organic PSs. The development of organic PSs molecules, however, is limited by the small δ, poor water solubility, and slow ISC process.…”

Section: Introductionmentioning

confidence: 99%

Theoretical Investigation of Ru(II) Complexes with Long Lifetime and a Large Two-Photon Absorption Cross-Section in Photodynamic Therapy

et al. 2023

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Two-photon photodynamic therapy (TP-PDT), as a new method for cancer, has shown unique advantages in tumors. A low two-photon absorption cross-section (δ) in the biologic spectral window and a short triplet state lifetime are the important issues faced by the current photosensitizers (PSs) in TP-PDT. In this paper, the photophysical properties of a series of Ru(II) complexes were studied by density functional theory and time-dependent density functional theory methods. The electronic structure, one- and two-photon absorption properties, type I/II mechanisms, triplet state lifetime, and solvation free energy were calculated. The results showed that the substitution of methoxyls by pyrene groups greatly improved the lifetime of the complex. Furthermore, the addition of acetylenyl groups subtly enhanced δ. Overall, complex 3b possess a large δ(1376 GM), a long lifetime (136 μs), and better solvation free energy. It is hoped that it can provide valuable theoretical guidance for the design and synthesis of efficient two-photon PSs in the experiment.

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Ru(II) containing photosensitizers for photodynamic therapy: A critique on reporting and an attempt to compare efficacy

Cited by 40 publications

References 150 publications

More-Is-Better Strategy for Constructing Homoligand Polypyridyl Ruthenium Complexes as Photosensitizers for Infrared Two-Photon Photodynamic Therapy

More-Is-Better Strategy for Constructing Homoligand Polypyridyl Ruthenium Complexes as Photosensitizers for Infrared Two-Photon Photodynamic Therapy

Recent Progress in Photodynamic Immunotherapy with Metal‐Based Photosensitizers

Theoretical Investigation of Ru(II) Complexes with Long Lifetime and a Large Two-Photon Absorption Cross-Section in Photodynamic Therapy

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