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.

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

2019 ◽  
Vol 23 (01n02) ◽  
pp. 34-45 ◽  
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.

scholarly journals Photophysical Properties of Pheophorbide-a Derivatives and Their Photodynamic Therapeutic Effects on a Tumor Cell LineIn Vitro

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Kang-Kyun Wang ◽  
Jing Li ◽  
Bong-Jin Kim ◽  
Jeong-Hyun Lee ◽  
Hee-Won Shin ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Triplet State ◽  
Singlet Oxygen ◽  
Alkyl Group ◽  
Photophysical Properties ◽  
Hydroxyl Group ◽  
Quantum Yields ◽  
Therapeutic Effects ◽  
Pheophorbide A

Pheophorbide-a derivatives have been reported to be potential photosensitizers for photodynamic therapy (PDT). In this study, photophysics of pheophorbide-a derivatives (PaDs) were investigated along with their photodynamic tumoricidal effectin vitro. PaDs were modified by changing the coil length and/or making the hydroxyl group (–OH) substitutions. Their photophysical properties were studied by steady-state and time-resolved spectroscopic methods. The photodynamic tumoricidal effect was evaluated in the mouse breast cancer cell line (EMT6). Lifetime and quantum yield of fluorescence and quantum yields of triplet state and singlet oxygen were studied to determine the dynamic energy flow. The coil length of the substituted alkyl group did not significantly affect the spectroscopic properties. However, the substitution with the hydroxyl group increased the quantum yields of the triplet state and the singlet oxygen due to the enhanced intersystem crossing. In order to check the application possibility as a photodynamic therapy agent, the PaDs with hydroxyl group were studied for the cellular affinity and the photodynamic tumoricidal effect of EMT6. The results showed that the cellular affinity and the photodynamic tumoricidal effect of PaDs with the hydroxyl group depended on the coil-length of the substituted alkyl group.

Fluorescein-entrapped magnetosomes for magnetically assisted photodynamic therapy

Nanomedicine ◽  
2021 ◽  
Author(s):  
Parul ◽  
Tapas Sen ◽  
Indrajit Roy
Keyword(s):  
Photodynamic Therapy ◽  
Iron Oxide ◽  
Singlet Oxygen ◽  
Blue Light ◽  
Cellular Uptake ◽  
Oxide Nanoparticles ◽  
In Vitro Methods ◽  
Magnetic Guidance ◽  
Magnetically Assisted

Aim: We investigated the application of fluorescein (FL)-entrapped magnetosomes, in other words, silica-coated iron oxide nanoparticles entrapped within niosomes (SIO/NIO), in magnetically assisted photodynamic therapy (PDT) in vitro. Methods: Panc-1 cells were treated with the magnetosomes, with and without external magnetic guidance, and irradiated with blue light. Results & conclusion: Upon photoactivation, the FL-entrapped magnetosomes can produce higher singlet oxygen in comparison to FL-entrapped micelles, probably due to the higher release tendency of the photosensitizer from the former. In vitro studies in Panc-1 cells revealed magnetically assisted enhancement in the cellular uptake of the magnetosomes. Magnetic assistance also led to enhancement in PDT efficiency in cells treated with the FL-entrapped magnetosomes and light, thus highlighting their potential in PDT.

INFLUENCE OF SUBSTITUTIONS IN ASYMMETRIC PORPHYRINS ON INTRACELLULAR UPTAKE, SUBCELLULAR LOCALIZATION AND PHOTOTOXICITY IN HELA CELLS

2008 ◽  
Vol 20 (01) ◽  
pp. 9-17 ◽  
Author(s):  
Cheng-Liang Peng ◽  
Ping-Shan Lai ◽  
Ming-Jium Shieh
Keyword(s):  
Photodynamic Therapy ◽  
Singlet Oxygen ◽  
Biomedical Application ◽  
Intracellular Localization ◽  
Cell Uptake ◽  
Quantum Yields ◽  
Log P ◽  
Potential Candidate ◽  
Porphyrin Derivatives

The asymmetric porphyrins with different substituents show various bioactivities in biomedical application. In this study, a series of asymmetric porphyrins with varying proportion of substituents, such as hydroxyphenyl and aminophenyl, were synthesized and characterized to evaluate their cell uptake, intracellular localization, cytotoxicities and phototoxicities in vitro. Among these synthesized porphyrins, 5-(4-aminophenyl)-10,15,20-tri-(4-hydroxyphenyl)-21,23H-porphyrin (porphyrin 5), which was mainly localized in mitochondria and with high quantum yields of singlet oxygen, is a potential candidate for photodynamic therapy. The effective phototoxicity of porphyrin 5 is mainly due to the higher extent in the cells and the selective mitochondria-localization. Comparing the partition coefficients of porphyrin derivatives, the best cellular uptake performs apparently with a partition coefficient (log p) ranging from about 1.7 to 1.9. In summary, higher quantum yields of singlet oxygen, and more specific mitochondrial localization of porphyrin 5 demonstrate its potential application in photodynamic therapy.

Synthesis and Biological Evaluations of Organoruthenium Scaffolds: A Comprehensive Update

2018 ◽  
Vol 15 (2) ◽  
pp. 179-207
Author(s):  
Ashaparna Mondal ◽  
Priyankar Paira
Keyword(s):  
Singlet Oxygen ◽  
Anticancer Agents ◽  
Ruthenium Complexes ◽  
Chemotherapeutic Agents ◽  
Quantum Yields ◽  
Ros Generation ◽  
Standard Drug ◽  
Cellular Environment ◽  
Theranostic Agents

Background: Currently ruthenium complexes are immerging as effective anticancer agents due to their less toxicity, better antiproliferative and antimetastatic activity, better stability in cellular environment and most importantly variable oxidation and co-ordination states of ruthenium allows binding this molecule with a variety of ligands. So in past few years researchers have shifted their interest towards organoruthenium complexes having good fluorescent profile that may be applicable for cancer theranostics. Nowadays, photodynamic therapy has become more acceptable because of its easy and effective approach towards killing cancer cells. Objective: Objective of this review article is to shed light on synthesis, characterization, stability and fluorescence studies of various ruthenium [Ru(II) and Ru(III)] complexes and different bioactivity studies conducted with the synthesized compounds to test their candidacy as potent chemotherapeutic agents. Methods: Various heterocyclic ligands containing N,O and S as heteroatom mainly were prepared and subjected to complexation with ruthenium-p-cymene moiety. In most cases [Ru(η6-p-cymene)(µ-Cl)Cl]2 was used as ruthenium precursor and the reactions were conducted in various alcohol medium such as methanol, ethanol or propanol. The synthesized complexes were characterized by 1H NMR and 13C NMR spectroscopy, GC-MS, ESI-MS, elemental analysis and single crystal X-ray crystallography methods. Fluorescence study and stability study were conducted accordingly using water, PBS buffer or DMSO. Stable compounds were considered for cell viability studies. To study the efficacy of the compounds in ROS generation as photosensitizers, in few cases, singlet oxygen quantum yields in presence of light were calculated. Suitable compounds were selected for in vitro & in vivo antiproliferative, anti-invasive activity studies. Result: Many newly synthesized compounds were found to have less IC50 compared to a standard drug cysplatin. Those compounds were also stable preferably in physiological conditions. Good fluorescence profile and ROS generation ability were observed for few compounds. Conclusion: Numerous ruthenium complexes were developed which can be used as cancer theranostic agents. Few molecules were synthesized as photosensitizers which were supposed to generate reactive singlet oxygen species in targeted cellular environment in presence of a particular type of light and thereby ceasing cancer cell growth.

scholarly journals Ruthenium-based PACT agents based on bisquinoline chelates: synthesis, photochemistry, and cytotoxicity

2021 ◽  
Author(s):  
Anja Busemann ◽  
Ingrid Flaspohler ◽  
Xue-Quan Zhou ◽  
Claudia Schmidt ◽  
Sina K. Goetzfried ◽  
...  
Keyword(s):  
Quantum Yield ◽  
Singlet Oxygen ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Ruthenium Complex ◽  
Human Cancer ◽  
Light Irradiation ◽  
Quantum Yields ◽  
Light Activation ◽  
Human Cancer Cells

AbstractThe known ruthenium complex [Ru(tpy)(bpy)(Hmte)](PF6)2 ([1](PF6)2, where tpy = 2,2’:6’,2″-terpyridine, bpy = 2,2’-bipyridine, Hmte = 2-(methylthio)ethanol) is photosubstitutionally active but non-toxic to cancer cells even upon light irradiation. In this work, the two analogs complexes [Ru(tpy)(NN)(Hmte)](PF6)2, where NN = 3,3'-biisoquinoline (i-biq, [2](PF6)2) and di(isoquinolin-3-yl)amine (i-Hdiqa, [3](PF6)2), were synthesized and their photochemistry and phototoxicity evaluated to assess their suitability as photoactivated chemotherapy (PACT) agents. The increase of the aromatic surface of [2](PF6)2 and [3](PF6)2, compared to [1](PF6)2, leads to higher lipophilicity and higher cellular uptake for the former complexes. Such improved uptake is directly correlated to the cytotoxicity of these compounds in the dark: while [2](PF6)2 and [3](PF6)2 showed low EC50 values in human cancer cells, [1](PF6)2 is not cytotoxic due to poor cellular uptake. While stable in the dark, all complexes substituted the protecting thioether ligand upon light irradiation (520 nm), with the highest photosubstitution quantum yield found for [3](PF6)2 (Φ[3] = 0.070). Compounds [2](PF6)2 and [3](PF6)2 were found both more cytotoxic after light activation than in the dark, with a photo index of 4. Considering the very low singlet oxygen quantum yields of these compounds, and the lack of cytotoxicity of the photoreleased Hmte thioether ligand, it can be concluded that the toxicity observed after light activation is due to the photoreleased aqua complexes [Ru(tpy)(NN)(OH2)]2+, and thus that [2](PF6)2 and [3](PF6)2 are promising PACT candidates. Graphic abstract

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>

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