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

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.

scholarly journals Novel meso-substituted porphyrin derivatives and its potential use in photodynamic therapy of cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
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.

Synthesis and photophysical properties of amphiphilic halogenated bacteriochlorins: new opportunities for photodynamic therapy of cancer

2009 ◽  
Vol 13 (04n05) ◽  
pp. 567-573 ◽  
Author(s):  
Mariette M. Pereira ◽  
Carlos J.P. Monteiro ◽  
Ana V.C. Simões ◽  
Sara M.A. Pinto ◽  
Luís G. Arnaut ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Photophysical Properties ◽  
Synergetic Effect ◽  
In Vitro Cytotoxicity ◽  
Recent Contribution ◽  
Photodynamic Therapy Of Cancer ◽  
Promising Treatment ◽  
Potential Use ◽  
Effect Of Light

Photodynamic therapy (PDT) is a promising treatment for several types of cancers. It involves the synergetic effect of light, oxygen and an appropriate photosensitizer. Extensive studies on the synthetic modulation of the structure of tetrapyrrolic macrocycles allowed for the optimization of chemical and physical properties of such photosensitizers. The progress from porphyrins to chlorins and more recently to bacteriochlorins clearly shows the improvements achieved in PDT photosensitizers. This paper summarizes our recent contribution to the synthesis of stable amphiphilic halogenated meso-tetraarylbacteriochlorins. Their photophysics, in vitro cytotoxicity and phototoxicity are presented and their potential use as photosensitizer for PDT application is assessed.

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

2020 ◽  
Author(s):  
Deborah A. Smithen ◽  
Susan Monro ◽  
Mitch Pinto ◽  
John A. Roque III ◽  
Roberto M. Diaz-Rodriguez ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Visible Light ◽  
Red Light ◽  
Visible Region ◽  
Hl60 Cell ◽  
Quantum Yields ◽  
Human Leukemia ◽  
New Family ◽  
Hl60 Cell Line

A new family of ten dinuclear Ru(II) complexes based on the bis[pyrrolyl Ru(II)] triad scaffold, where two Ru(bpy)<sub>2</sub> 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) ≥10<sup>4</sup> 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 EC<sub>50</sub> 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<sup>-2</sup>, 7.8 mW cm<sup>-2</sup>) and 625-nm red (100 J cm<sup>-2</sup>, 42 mW cm<sup>-2</sup>) 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<sup>-2</sup>, 28 mW cm<sup>-2</sup>). 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 (EC<sub>50</sub>=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 EC<sub>50</sub> values and PIs >300 against <i>S. mutans</i> and <i>S. aureus </i>were obtained with visible light. This activity was attenuated with 625-nm red light, but PIs were still near 50. The ligand-localized <sup>3</sup>ππ* state contributed by the pyrenyl linker of 5h likely plays a key role in its phototoxic effects toward cancer cells and bacteria.<br><br>

scholarly journals A long-lived cuprous bis-phenanthroline complex for the photodynamic therapy of cancer

2018 ◽  
Vol 47 (14) ◽  
pp. 4959-4967 ◽  
Author(s):  
Cynthia Al Hageh ◽  
Majd Al Assaad ◽  
Zeinab El Masri ◽  
Nawar Samaan ◽  
Mirvat El-Sibai ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Photodynamic Therapy Of Cancer ◽  
Earth Abundant ◽  
Phenanthroline Complex ◽  
Potential Use

An earth-abundant cuprous bis-phenanthroline photosensitizer showed potential use in the photodynamic therapy of cancer.

2,4,6-Triarylchalcogenopyrylium Dyes Related in Structure to the Antitumor Agent AA1 as in Vitro Sensitizers for the Photodynamic Therapy of Cancer

1999 ◽  
Vol 42 (19) ◽  
pp. 3942-3952 ◽  
Author(s):  
Kristi A. Leonard ◽  
Marina I. Nelen ◽  
Linda T. Anderson ◽  
Scott L. Gibson ◽  
Russell Hilf ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Antitumor Agent ◽  
Photodynamic Therapy Of Cancer

scholarly journals Photosensitization of a subcutaneous tumour by the natural anthraquinone parietin and blue light

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
María Laura Mugas ◽  
Gustavo Calvo ◽  
Juliana Marioni ◽  
Mariela Céspedes ◽  
Florencia Martinez ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Blue Light ◽  
Tumour Growth ◽  
Normal Skin ◽  
Multiple Comparisons ◽  
Leukemic Cells ◽  
Growth Delay ◽  
Cell Growth And Migration ◽  
Superficial Area

AbstractPhotodynamic therapy (PDT) is an anticancer treatment involving administration of a tumour-localizing photosensitizer, followed by activation by light of a suitable wavelength. In previous work, we showed that the natural anthraquinone (AQ) Parietin (PTN), was a promising photosensitizer for photodynamic therapy of leukemic cells in vitro. The present work aimed to analyze the photosensitizing ability of PTN in the mammary carcinoma LM2 cells in vitro and in vivo in a model of subcutaneously implanted tumours. Photodynamic therapy mediated by parietin (PTN-PDT) (PTN 30 µM, 1 h and 1.78 J/cm2 of blue light) impaired cell growth and migration of LM2 cells in vitro. PTN per se induced a significant decrease in cell migration, and it was even more marked after illumination (migration index was 0.65 for PTN and 0.30 for PTN-PDT, *p < 0.0001, ANOVA test followed by Tukey’s multiple comparisons test), suggesting that both PTN and PTN-PDT would be potential inhibitors of metastasis. Fluorescence microscopy observation indicated cytoplasmic localization of the AQ and no fluorescence at all was recorded in the nuclei. When PTN (1.96 mg) dissolved in dimethyl sulfoxide was topically applied on the skin of mice subcutaneously implanted with LM2 cells, PTN orange fluorescence was strongly noticed in the stratum corneum and also in the inner layers of the tumour up to approximately 5 mm. After illumination with 12.74 J/cm2 of blue light, one PDT dose at day 1, induced a significant tumour growth delay at day 3, which was not maintained in time. Therefore, we administered a second PTN-PDT boost on day 3. Under these conditions, the delay of tumour growth was 28% both on days 3 and 4 of the experiment (*p < 0.05 control vs. PTN-PDT, two-way ANOVA, followed by Sidak’s multiple comparisons test). Histology of tumours revealed massive tumour necrosis up to 4 mm of depth. Intriguingly, a superficial area of viable tumour in the 1 mm superficial area, and a quite conserved intact skin was evidenced. We hypothesize that this may be due to PTN aggregation in contact with the skin and tumour milieu of the most superficial tumour layers, thus avoiding its photochemical properties. On the other hand, normal skin treated with PTN-PDT exhibited slight histological changes. These preliminary findings encourage further studies of natural AQs administered in different vehicles, for topical treatment of cutaneous malignancies.

scholarly journals The Cellular Uptake of Sensitizers Bound to Cyclodextrin Carriers

2004 ◽  
Vol 47 (4) ◽  
pp. 313-315 ◽  
Author(s):  
Hana Kolářová ◽  
Martin Huf ◽  
Jaroslav Maceček ◽  
Pavla Nevřelová ◽  
Marek Tomečka ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cellular Uptake ◽  
Morphological Changes ◽  
Time Interval ◽  
Fluorescent Microscope ◽  
Photodynamic Therapy Of Cancer ◽  
Plate Reader ◽  
Hydroxypropyl Cyclodextrins ◽  
The Given

Photodynamic therapy of cancer uses the interaction of sensitizers and light to destroy cancer cells. In this study we tested the cellular uptake of meso-tetrakis(4-sulfonatophenyl)porphine (TPPS4) and its complex PdTPPS4 in the presence or absence of 2–hydroxypropyl-cyclodextrins (hpCDs) on G361 human melanoma cells. Self-fluorescence in G361 cells were measured by Perkin-Elmer LS50B luminometer equipped with well plate reader accessory. Morphological changes in cells have been evaluated using inversion fluorescent microscope Olympus IX 70 and image analysis. The uptake of the sensitizer PdTPPS4 at the given time interval from 1 to 48 hours is markedly higher than the uptake of TPPS4. The highest uptake was found for sensitizer PdTPPS4 in combination with hpβCD. TPPS4 and PdTPPS4 especially in the supramolecular complex with nontoxic cyclodextrin carriers represent efficient sensitizers for photodynamic therapy in vitro on G361 cells.

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

2019 ◽  
Vol 23 (11n12) ◽  
pp. 1505-1514 ◽  
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.

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

2018 ◽  
Vol 22 (09n10) ◽  
pp. 807-813 ◽  
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.

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

2019 ◽  
Vol 9 (24) ◽  
pp. 5414 ◽  
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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