Bis[Pyrrolyl Ru(II)] Triads: a New Class of Photosensitizers for Metal-Organic Photodynamic Therapy

A new family of ten dinuclear Ru(II) complexes based on the bis[pyrrolyl Ru(II)] triad scaffold, where two Ru(bpy)2 centers are separated by a variety of organic linkers, was prepared to evaluate the influence of the organic chromophore on the spectroscopic and in vitro photodynamic therapy (PDT) properties of the compounds. The bis[pyrrolyl Ru(II)] triads absorbed strongly throughout the visible region, with several members having molar extinction coefficients (e) ≥104 at 600–620 nm and longer. Phosphorescence quantum yields were generally less than 0.1% and in some cases undetectable. The singlet oxygen quantum yields ranged from 5% to 77% and generally correlated with their photocytotoxicities toward human leukemia (HL-60) cells regardless of the wavelength of light used. Dark cytotoxicities varied ten-fold, with EC50 values in the range of 10–100 µM and phototherapeutic indices (PIs) as large as 5,400 and 260 with broadband visible (28 J cm-2, 7.8 mW cm-2) and 625-nm red (100 J cm-2, 42 mW cm-2) light, respectively. The bis[pyrrolyl Ru(II)] triad with a pyrenyl linker (5h) was especially potent, with an EC50 value of 1 nM and PI >27,000 with visible light and subnanomolar activity with 625-nm light (100 J cm-2, 28 mW cm-2). The lead compound 5h was also tested in a tumor spheroid assay using the HL60 cell line and exhibited greater photocytotoxcicity in this more resistant model (EC50=60 nM and PI>1,200 with 625-nm light) despite a lower dark cytotoxicity. The in vitro PDT effects of 5h extended to bacteria, where submicromolar EC50 values and PIs >300 against S. mutans and S. aureus were obtained with visible light. This activity was attenuated with 625-nm red light, but PIs were still near 50. The ligand-localized 3ππ* state contributed by the pyrenyl linker of 5h likely plays a key role in its phototoxic effects toward cancer cells and bacteria.

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TLD1433-Mediated Photodynamic Therapy with an Optical Surface Applicator in the Treatment of Lung Cancer Cells In Vitro

Pharmaceuticals ◽

10.3390/ph13070137 ◽

2020 ◽

Vol 13 (7) ◽

pp. 137 ◽

Cited By ~ 1

Author(s):

Sarah Chamberlain ◽

Houston D. Cole ◽

John Roque ◽

David Bellnier ◽

Sherri A. McFarland ◽

...

Keyword(s):

Lung Cancer ◽

Photodynamic Therapy ◽

Cell Viability ◽

Light Propagation ◽

Residual Disease ◽

Red Light ◽

Optical Surface ◽

Light Fluence ◽

532 Nm

Intra-operative photodynamic therapy (IO-PDT) in combination with surgery for the treatment of non-small cell lung cancer and malignant pleural mesothelioma has shown promise in improving overall survival in patients. Here, we developed a PDT platform consisting of a ruthenium-based photosensitizer (TLD1433) activated by an optical surface applicator (OSA) for the management of residual disease. Human lung adenocarcinoma (A549) cell viability was assessed after treatment with TLD1433-mediated PDT illuminated with either 532- or 630-nm light with a micro-lens laser fiber. This TLD1433-mediated PDT induced an EC50 of 1.98 μM (J/cm2) and 4807 μM (J/cm2) for green and red light, respectively. Cells were then treated with 10 µM TLD1433 in a 96-well plate with the OSA using two 2-cm radial diffusers, each transmitted 532 nm light at 50 mW/cm for 278 s. Monte Carlo simulations of the surface light propagation from the OSA computed light fluence (J/cm2) and irradiance (mW/cm2) distribution. In regions where 100% loss in cell viability was measured, the simulations suggest that >20 J/cm2 of 532 nm was delivered. Our studies indicate that TLD1433-mediated PDT with the OSA and light simulations have the potential to become a platform for treatment planning for IO-PDT.

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Toluidine blue O and porphyrin-mediated photodynamic therapy on three main pathogenic bacteria of periodontitis using portable LED phototherapy device

Journal of Innovative Optical Health Sciences ◽

10.1142/s1793545815500170 ◽

2015 ◽

Vol 08 (04) ◽

pp. 1550017 ◽

Cited By ~ 3

Author(s):

Xuewei Jiang ◽

Zhichao Fan ◽

Yili Yu ◽

Chenying Shao ◽

Yuanzhen Suo ◽

...

Keyword(s):

Photodynamic Therapy ◽

Toluidine Blue ◽

Pathogenic Bacteria ◽

Light Emitting Diode ◽

Red Light ◽

In Vitro Screening ◽

Light Emitting ◽

Led Phototherapy ◽

Prevotella Melaninogenica

Photodynamic therapy (PDT) has been commonly used in treating many diseases, such as cancer and infectious diseases. We investigated the different effects of PDT on three main pathogenic bacteria of periodontitis — Prevotella melaninogenica (P.m.), Porphyromonas gingivalis (P.g.) and Aggregatibacter actinomycetemcomitans (A.a.). The portable red light-emitting diode (LED) phototherapy device was used to assess the exogenous PDT effects with different light doses and photosensitizer concentrations (Toluidine blue O, TBO). The portable blue LED phototherapy device was used to assess the endogenous PDT effects with the use of endogenous photosensitizers (porphyrin) under different light doses. We found out that both exogenous and endogenous PDT were able to restrict the growth of all the three bacteria significantly. Moreover, the optimal PDT conditions for these bacteria were obtained through this in vitro screening and could guide the clinical PDT on periodontitis.

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Mitochondria-targeted porphyrin-based photosensitizers containing triphenylphosphonium cations showing efficient in vitro photodynamic therapy effects

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424619501682 ◽

2019 ◽

Vol 23 (11n12) ◽

pp. 1505-1514 ◽

Cited By ~ 1

Author(s):

Xing Guo ◽

Hao Wu ◽

Wei Miao ◽

Yangchun Wu ◽

Erhong Hao ◽

...

Keyword(s):

Photodynamic Therapy ◽

Cancer Therapy ◽

Fluorescence Spectroscopy ◽

Hela Cells ◽

Photophysical Properties ◽

Quantum Yields ◽

Subcellular Organelle

Subcellular organelle-targeted photosensitizers have recently reported to be effective photodynamic therapy (PDT) agents. In this work, three porphyrin-derived photosensitizers, containing one, two or four triphenylphosphonium targeting groups, were synthesized and characterized by NMR, HRMS, UV-vis and fluorescence spectroscopy. These photosensitizers showed similar photophysical properties to classical porphyrins and exhibited excellent [Formula: see text]O[Formula: see text] quantum yields in acetonitrile. Subcellular colocalization indicated that all three photosensitizers specifically stain the mitochondria of HeLa cells. Photosensitizer mito-dp, containing two triphenylphosphonium cations was found to be the most uptaken by cells and exhibited the best PDT effect with an effective phototoxicity (IC[Formula: see text] (light) [Formula: see text] 12.4 nM), suggestive of a higher practicable potential of mitochondria-targeted PDT agents in cancer therapy.

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Novel Meso-substituted Porphyrin Derivatives and its Potential use in Photodynamic Therapy of Cancer

10.21203/rs.3.rs-531250/v1 ◽

2021 ◽

Author(s):

Pablo Vallecorsa ◽

Gabriela Di Venosa ◽

M. Belén Ballatore ◽

Dario Ferreyra ◽

Leandro Mamone ◽

...

Keyword(s):

Photodynamic Therapy ◽

Normal Skin ◽

Hair Follicles ◽

Systemic Administration ◽

Mammary Adenocarcinoma ◽

Quantum Yields ◽

High Accumulation ◽

Photodynamic Therapy Of Cancer ◽

Potential Use

Abstract Background: Photodynamic therapy (PDT) is an anticancer treatment that utilizes the interaction of light and a photosensitiser (PS), promoting tumour cell death mediated by generation of reactive oxygen species. In this study, we evaluated the in vitro photoactivity of four meso-substituted porphyrins and a porphyrin coupled to a fullerene. Methods: The cell line employed was the LM3 mammary adenocarcinoma, and the PS with the best photokilling activity was administered to mice bearing the LM3 subcutaneously implanted adenocarcinoma. The TEMCP4+ porphyrin and its analogue TEMCC4+ chlorine contain four identical carbazoyl substituents at the meso positions of the tetrapyrrolic macrocycle and have A4 symmetry. The TAPP derivative also has A4 symmetry, and it is substituted at the meso positions by aminopropoxy groups. The DAPP molecule has ABAB symmetry with aminopropoxy and the trifluoromethyl substituents in trans positions. The TCP-C604+ dyad is formed by a porphyrin unit covalently attached to the fullerene C60.Results: The PSs are taken up by the cells with the following efficiency: TAPP> TEMCP4+= TEMCC4+> DAPP >TCP-C604+, and the amount of intracellular PS correlates fairly with the photodamage degree, but also the quantum yields of singlet oxygen influence the PDT outcome. TAPP, DAPP, TEMCC4+ and TEMCP4+ exhibit high photoactivity against LM3 mammary carcinoma cells, being TAPP the most active. After topical application of TAPP on the skin of mice bearing LM3 tumours, the molecule is localized mainly in the stratum corneum, and at a lower extent in hair follicles and sebaceous glands. Systemic administration of TAPP produces a tumour: normal skin ratio of 31.4, and high accumulation in intestine and lung.Conclusion: The results suggest a potential use of topical TAPP for the treatment of actinic keratosis and skin adnexal neoplasms. In addition, selectivity for tumour tissue after systemic administration highlights the selectivity of and potentiality of TAPP as a new PS.

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Quinolin-8-yloxy-substituted zinc(II) phthalocyanines for enhanced in vitro photodynamic therapy

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424618500669 ◽

2018 ◽

Vol 22 (09n10) ◽

pp. 807-813 ◽

Cited By ~ 2

Author(s):

Juanjuan Chen ◽

Yuting Fang ◽

Hong Liu ◽

Naisheng Chen ◽

Shengping Chen ◽

...

Keyword(s):

Photodynamic Therapy ◽

Singlet Oxygen ◽

Clinical Application ◽

Cellular Uptake ◽

Culture Medium ◽

Anticancer Agent ◽

Quantum Yields ◽

Anticancer Efficacy ◽

Self Aggregation

Photodynamic therapy (PDT) is an innovative and promising modality to treat various tumors. In this study, two novel zinc(II) phthalocyanines substituted with quinolin-8-yloxy groups at the [Formula: see text]-position, namely mono(quinolin-8-yloxy) zinc(II) phthalocyanine (ZnPc-Q1) and tetra(quinolin-8-yloxy) zinc(II) phthalocyanine (ZnPc-Q4), have been synthesized and fully characterized. With quinolin-8-yloxy, these two phthalocyanines exhibit less self-aggregation in DMF and culture medium, high singlet oxygen quantum yields, mitochondria localization and high photodynamic activities (IC[Formula: see text] values as low as 2 nM). Compared to ZnPc-Q4, ZnPc-Q1 exhibits higher cellular uptake and lower IC[Formula: see text] values. Benefitting from its higher anticancer efficacy and lack of isomers, ZnPc-Q1 is a highly promising anticancer agent in clinical application.

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Photophysicochemical Properties and In Vitro Phototherapeutic Effects of Iodoquinoline- and Benzothiazole-Derived Unsymmetrical Squaraine Cyanine Dyes

Applied Sciences ◽

10.3390/app9245414 ◽

2019 ◽

Vol 9 (24) ◽

pp. 5414 ◽

Cited By ~ 1

Author(s):

Sofia Friães ◽

Eurico Lima ◽

Renato E. Boto ◽

Diana Ferreira ◽

José R. Fernandes ◽

...

Keyword(s):

Photodynamic Therapy ◽

Singlet Oxygen ◽

Cell Lines ◽

Light Emitting Diode ◽

Cyanine Dyes ◽

Quantum Yields ◽

Light Emitting ◽

Diode System ◽

Hepg2 Cell Lines

The search to replace conventional cancer treatment therapies, such as chemotherapy, radiotherapy and surgery has led over the last ten years, to a substantial effort in the development of several classes of photodynamic therapy photosensitizers with desired photophysicochemical and photobiological properties. Herein we report the synthesis of 6-iodoquinoline- and benzothiazole-based unsymmetrical squaraine cyanine dyes functionalized with amine groups located in the four-membered central ring. Their photodegradation and singlet oxygen production ability, as well as their in vitro photocytotoxicity against Caco-2 and HepG2 cell lines using a 630.8 ± 0.8 nm centered light-emitting diode system, were also investigated. All photosensitizer candidates displayed strong absorption within the tissue transparency spectral region (650–850 nm). The synthesized dyes were found to have moderate light stability. The potential of these compounds is evidenced by their cytotoxic activity against both tumor cell lines, highlighting the zwitterionic unsubstituted dye, which showed more intense photodynamic activity. Although the singlet oxygen quantum yields of these iodinated derivatives are considered low, it could be concluded that their introduction into the quinoline heterocycle was highly advantageous as it played a role in increasing selective cytotoxicity in the presence of light. Thus, the novel synthesized dyes present photophysicochemical and in vitro photobiological properties that make them excellent photosensitizer candidates for photodynamic therapy.

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Photophysicochemical properties and photodynamic therapy activity of chloroindium(III) tetraarylporphyrins and their gold nanoparticle conjugates

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424618501146 ◽

2019 ◽

Vol 23 (01n02) ◽

pp. 34-45 ◽

Cited By ~ 8

Author(s):

Rodah C. Soy ◽

Balaji Babu ◽

David O. Oluwole ◽

Njemuwa Nwaji ◽

James Oyim ◽

...

Keyword(s):

Photodynamic Therapy ◽

Quantum Yield ◽

Singlet Oxygen ◽

Dose Range ◽

Heavy Atom ◽

Therapeutic Window ◽

Quantum Yields ◽

Yield Values ◽

Yield Formula

Novel chloroindium(III) complexes of tetra(4-methylthiophenyl)porphyrin (2a) and tetra-2-thienylporphyrin (2b) dyes have been synthesized and characterized. The main goal of the project was to identify fully symmetric porphyrin dyes with Q-band regions that lie partially in the therapeutic window that are suitable for use in photodynamic therapy (PDT). 2a and 2b were found to have fluorescence quantum yield values [Formula: see text] 0.01 and moderately high singlet oxygen quantum yields (0.54−0.73) due to heavy atom effects associated with the sulfur and indium atoms. The dark toxicity and PDT activity against epithelial breast cancer cells (MCF-7) were investigated over a dose range of 3.0−40 [Formula: see text]g [Formula: see text] mL[Formula: see text]. The in vitro dark cytotoxicity of 2a is significantly lower than that of 2b at [Formula: see text] 40 [Formula: see text]g [Formula: see text] mL[Formula: see text]. 2a was conjugated with gold nanoparticles (AuNPs) to form a nanoconjugate (2a-AuNPs), which exhibited a higher singlet oxygen quantum yield ([Formula: see text] value and PDT activity than was observed for 2a alone. The results suggest that the AuNPs nanoconjugates of readily synthesized fully symmetric porphyrin dyes are potentially suitable for PDT applications, if meso-aryl substituents that provide scope for nanoparticle conjugation can be introduced that shift the Q bands into the therapeutic window.

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