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1.
Biochim Biophys Acta Bioenerg ; 1861(10): 148234, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32485158

RESUMO

Photosystem II (PS II) catalyzes the light-driven process of water splitting in oxygenic photosynthesis. Four core membrane-spanning proteins, including D1 that binds the majority of the redox-active co-factors, are surrounded by 13 low-molecular-weight (LMW) proteins. We previously observed that deletion of the LMW PsbT protein in the cyanobacterium Synechocystis sp. PCC 6803 slowed electron transfer between the primary and secondary plastoquinone electron acceptors QA and QB and increased the susceptibility of PS II to photodamage. Here we show that photodamaged ∆PsbT cells exhibit unimpaired rates of oxygen evolution if electron transport is supported by HCO3- even though the cells exhibit negligible variable fluorescence. We find that the protein environment in the vicinity of QA and QB is altered upon removal of PsbT resulting in inhibition of QA- oxidation in the presence of 2,5-dimethyl-1,4-benzoquinone, an artificial PS II-specific electron acceptor. Thermoluminescence measurements revealed an increase in charge recombination between the S2 oxidation state of the water-oxidizing complex and QA- by the indirect radiative pathway in ∆PsbT cells and this is accompanied by increased 1O2 production. At the protein level, both D1 removal and replacement, as well as PS II biogenesis, were accelerated in the ∆PsbT strain. Our results demonstrate that PsbT plays a key role in optimizing the electron acceptor complex of the acceptor side of PS II and support the view that repair and biogenesis of PS II share an assembly pathway that incorporates both de novo synthesis and recycling of the assembly modules associated with the core membrane-spanning proteins.


Assuntos
Proteínas de Bactérias/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Synechocystis/metabolismo , Synechocystis/efeitos da radiação , Estabilidade Enzimática/efeitos da radiação , Luz/efeitos adversos , Oxigênio Singlete/metabolismo
2.
Arch Biochem Biophys ; 686: 108364, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32315653

RESUMO

Fucoxanthin (Fx), a major carotenoid found in brown seaweed, is known to show a unique and wide variety of biological activities. Upon absorption, Fx is metabolized to fucoxanthinol and amarouciaxanthin, and these metabolites mainly accumulate in visceral white adipose tissue (WAT). As seen in other carotenoids, Fx can quench singlet oxygen and scavenge a wide range of free radicals. The antioxidant activity is related to the neuroprotective, photoprotective, and hepatoprotective effects of Fx. Fx is also reported to show anti-cancer activity through the regulation of several biomolecules and signaling pathways that are involved in either cell cycle arrest, apoptosis, or metastasis suppression. Among the biological activities of Fx, anti-obesity is the most well-studied and most promising effect. This effect is primarily based on the upregulation of thermogenesis by uncoupling protein 1 expression and the increase in the metabolic rate induced by mitochondrial activation. In addition, Fx shows anti-diabetic effects by improving insulin resistance and promoting glucose utilization in skeletal muscle.


Assuntos
Suplementos Nutricionais/análise , Alga Marinha/química , Xantofilas/química , Xantofilas/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Descoberta de Drogas , Radicais Livres/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/metabolismo , Resistência à Insulina , Fígado/metabolismo , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Depuradores/metabolismo , Oxigênio Singlete/metabolismo , Proteína Desacopladora 1/química , Proteína Desacopladora 1/metabolismo , Xantofilas/efeitos adversos , beta Caroteno/análogos & derivados , beta Caroteno/química
3.
Electron. j. biotechnol ; 44: 14-18, Mar. 2020. ilus, graf
Artigo em Inglês | LILACS | ID: biblio-1087629

RESUMO

BACKGROUND: Although bioactive metabolites capable of causing oxidative photo-necrosis in plant tissues have been identified in fungi, little is known about this type of mechanism in bacteria. These metabolites act as photosensitizers that generate reactive oxygen species (ROS) capable of causing damage to cells. In addition, these metabolites can pass into an energetically excited state when they receive some luminous stimulus, a condition in which they interact with other molecules present in the environment, such as molecular oxygen (O2), also known as triplet oxygen (3 O2), generating ROS. RESULTS: The suspension of the bacterial culture of Pseudomonas cedrina was shown to produce foliar necrosis in papaya leaves (Carica papaya L.) only in the presence of sunlight, which is evidence of photosensitizing mechanisms that generate singlet oxygen (1 O2). From the chemical study of extracts obtained from this bacteria, 3-(4-(2-carboxipropyl) phenyl) but-2-enoic acid (1) was isolated. This compound, in the presence of light and triplet oxygen (3 O2), was able to oxidize ergosterol to its peroxide, since it acted as a photosensitizer producing 1 O2, with which it was corroborated that a photosensitization reaction occurs, mechanism by which this bacterium could prove to cause oxidative foliar photo-necrosis. CONCLUSIONS: P. cedrina was able to induce oxidative foliar photo-necrosis because of its potential ability to produce photosensitizing metabolites that generate singlet oxygen in the plants it colonizes. Based on the above, it can be proposed that some bacteria can cause oxidative foliar photo-necrosis as an important mechanism in the pathogenesis of host species.


Assuntos
Doenças das Plantas/microbiologia , Pseudomonas/fisiologia , Carica/microbiologia , Oxigênio Singlete/metabolismo , Pseudomonas/metabolismo , Ácidos , Espécies Reativas de Oxigênio , Folhas de Planta/microbiologia , Foto-Oxidação , Luz , Necrose
4.
Nanoscale ; 12(9): 5332-5340, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32090217

RESUMO

Bicontinuous nanospheres (BCNs) are underutilized self-assembled nanostructures capable of simultaneous delivery of both hydrophilic and hydrophobic payloads. Here, we demonstrate that BCNs assembled from poly(ethylene glycol)-block-poly(propylene sulfide) (PEG-b-PPS), an oxidation-sensitive copolymer, are stably retained within cell lysosomes following endocytosis, resisting degradation and payload release for days until externally triggered. The oxygen scavenging properties and enhanced stability of the bicontinuous PEG-b-PPS nanoarchitecture significantly protected cells from typically cytotoxic application of pro-apoptotic photo-oxidizer pheophorbide A and chemotherapeutic camptothecin. The photo-oxidation triggered transition from a bicontinuous to micellar morphology overcame this stability, allowing on-demand cytosolic delivery of camptothecin for enhanced control over off-on cytotoxicity. These results indicate that inducible transitions in the nanostructure morphology can influence intracellular stability and toxicity of self-assembled nanotherapeutics.


Assuntos
Citosol/metabolismo , Luz , Micelas , Nanoestruturas/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Camptotecina/química , Camptotecina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Clorofila/análogos & derivados , Clorofila/química , Clorofila/farmacologia , Portadores de Fármacos/química , Endocitose , Lisossomos/metabolismo , Camundongos , Oxirredução , Polietilenoglicóis/química , Células RAW 264.7 , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo , Sulfetos/química
5.
Nanoscale ; 12(9): 5587-5600, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32100776

RESUMO

As one of the most promising noninvasive therapeutic modalities, sonodynamic therapy (SDT) can focus the ultrasound energy on tumor sites located in deep tissue and locally activate the preloaded sonosensitizer to kill tumor cells. However, exploring sonosensitizers with high SDT efficacy and desirable biosafety is still a significant challenge. Herein, we utilized the hydrophilic-hydrophobic self-assembly technology to assemble the hydrophobic organic dye Ce6 and broad spectral anti-cancer agent Paclitaxel with hydrophilic organic dye IR783 to generate a nanoscale sonosensitizer, Ce6-PTX@IR783, without the introduction of extra nanomaterials into the fabrication to guarantee high therapeutic biosafety and further potential clinical translation. The constructed nanodrug was endowed with an external ultrasound-activatable chemo-sonodynamic effect and photoacoustic imaging performance via integrating multiple moieties into one nanosystem. Ce6 could enhance the sonodynamic effect, while PTX exerted a chemotherapeutic effect, and IR783 was applied to increase tumor-specific accumulation and assist in fulfilling photoacoustic imaging. In particular, the small particle size (70 nm) of Ce6-PTX@IR783 contributed to the increased tumor accumulation via the enhanced permeability and retention effect. The high synergistically chemo-sonodynamic therapeutic efficacy has been successfully demonstrated in vitro and in vivo, in addition to the demonstrated high biodegradability, biocompatibility and biosafety. This facile self-assembly procedure provides an intriguing strategy for highly efficient utilization of hydrophobic drugs and is liable to realize large-scale production and further clinical translation.


Assuntos
Antineoplásicos Fitogênicos/química , Nanopartículas/química , Paclitaxel/química , Porfirinas/química , Radiossensibilizantes/química , Nanomedicina Teranóstica/métodos , Animais , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Endocitose , Feminino , Corantes Fluorescentes/química , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Radiossensibilizantes/farmacologia , Radiossensibilizantes/uso terapêutico , Oxigênio Singlete/metabolismo , Distribuição Tecidual , Transplante Heterólogo
6.
Inorg Chem ; 59(6): 3919-3933, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32096986

RESUMO

We report the synthesis and photochemical and biological characterization of Ru(II) complexes containing π-expansive ligands derived from dimethylbenzo[i]dipyrido[3,2-a:2',3'-c]phenazine (Me2dppn) adorned with flanking aryl substituents. Late-stage Suzuki couplings produced Me2dppn ligands substituted at the 10 and 15 positions with phenyl (5), 2,4-dimethylphenyl (6), and 2,4-dimethoxyphenyl (7) groups. Complexes of the general formula [Ru(tpy)(L)(py)](PF6)2 (8-10), where L = 4-7, were characterized and shown to have dual photochemotherapeutic (PCT) and photodynamic therapy (PDT) behavior. Quantum yields for photodissociation of monodentate pyridines from 8-10 were about 3 times higher than that of parent complex [Ru(tpy)(Me2dppn)(py)](PF6)2 (1), whereas quantum yields for singlet oxygen (1O2) production were ∼10% lower than that of 1. Transient absorption spectroscopy indicates that 8-10 possess long excited state lifetimes (τ = 46-50 µs), consistent with efficient 1O2 production through population and subsequent decay of ligand-centered 3ππ* excited states. Complexes 8-10 displayed greater lipophilicity relative to 1 and association to DNA but do not intercalate between the duplex base pairs. Complexes 1 and 8-10 showed photoactivated toxicity in breast and prostate cancer cell lines with phototherapeutic indexes, PIs, as high as >56, where the majority of cell death was achieved 4 h after treatment with Ru(II) complexes and light. Flow cytometric data and rescue experiments were consistent with necrotic cell death mediated by the production of reactive oxygen species, especially 1O2. Collectively, this study confirms that DNA intercalation by Ru(II) complexes with π-expansive ligands is not required to achieve photoactivated cell death.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Antineoplásicos/efeitos da radiação , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , Complexos de Coordenação/efeitos da radiação , DNA/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Radical Hidroxila/metabolismo , Ligantes , Luz , Necrose/induzido quimicamente , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/metabolismo , Fármacos Fotossensibilizantes/efeitos da radiação , Rutênio/química , Oxigênio Singlete/metabolismo
7.
Chemistry ; 26(8): 1697, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31922634

RESUMO

Invited for the cover of this issue is the group of Torres at the University of Madrid. The image of the cover of this issue depicts cancer cells being destroyed by reactive singlet oxygen produced by ruthenium phthalocyanine glycoconjugates under red light. The work, developed at the Universities of Madrid, Aveiro, Lisbon and Coimbra, describes ruthenium phthalocyanines as powerful bladder cancer PDT agents. Read the full text of the article at 10.1002/chem.201903546.


Assuntos
Compostos Organometálicos/química , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/metabolismo , Humanos , Compostos Organometálicos/síntese química , Compostos Organometálicos/uso terapêutico , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico
8.
J Photochem Photobiol B ; 203: 111777, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31931387

RESUMO

Despite the high in vitro efficacy of photodynamic therapeutics, lack of tumor targeting significantly reduces their in vivo efficacy and thus limits their clinical use. Photoimmunotherapy (PIT) is a new synthetic strategy to target and treat cancer by photodynamic therapy (PDT). In this study, we describe design and synthesis of a third-generation photosensitizer comprising a PEGylated-phthalocyanine star-polymer photosensitizer that covalently bound to a myeloma tumor-selective antibody (MAb) via the carbodiimide chemistry. The free photosensitizer demonstrated a minimum dark toxicity when tested in mammalian myeloma cell line (SP2/OR); and a moderate phototoxicity after irradiation with non thermal laser red light as a result of light-induced production of cytotoxic singlet oxygen species. Covalent attachment of the photosensitizer (Pc) to the MAb resulted in a significantly enhanced phototoxicity. This is mainly ascribed to the fact that internalization enhances phototoxicity of Pc-MAb bioconjugates. The radioactivated photoimmuno-conjugates 131I(PcMAb) demonstrated the highest phototoxicity to myeloma cells. The suggested bioconjugates are promising candidates as multiple therapeutic models for in vivo treatment of myeloma.


Assuntos
Anticorpos Monoclonais/química , Indóis/química , Fármacos Fotossensibilizantes/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Imunoterapia , Indóis/farmacologia , Radioisótopos do Iodo/química , Marcação por Isótopo , Luz , Camundongos , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Oxigênio Singlete/metabolismo
9.
J Photochem Photobiol B ; 204: 111802, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31981990

RESUMO

Suitable properties as well as eco-friendly synthesis of photoluminescent Au nanoclusters (NCs) make them promising compounds for biomedical diagnostics and visualization applications. However, the potential photochemical activity of such agents on cancerous cells is largely unknown. The nanoclusters (BSA-Au NCs) were synthetized in the presence of BSA (an average hydrodynamic diameter was about 9.4 nm, while the size of the metal cluster was <1.3 nm according to atomic force microscopy measurements) and possessed a broad photoluminescence band at 680 nm in buffered (pH 7.2) aqueous medium. The photochemical activity was studied by adding two fluorescent probes (dihydrorhodamine or Singlet Oxygen Sensor Green) for detection of reactive oxygen species in samples irradiated at 405 nm to minimize direct excitation of the probes. The photoluminescence measurements evidenced the capability of BSA-Au NCs to generate reactive oxygen species upon light exposure, while the observed sensitivity of the photoluminescence properties might be used to indicate photooxidative processes in the medium. The viability test performed on breast cancer cells after incubation with BSA-Au NCs and subsequent irradiation revealed notable difference in induced phototoxicity between two cell lines, which was not the case after the corresponding treatment using the photosensitizer chlorin e6.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Espécies Reativas de Oxigênio/metabolismo , Soroalbumina Bovina/química , Oxigênio Singlete/metabolismo , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Feminino , Corantes Fluorescentes/química , Humanos , Lasers Semicondutores , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/toxicidade , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/química , Oxigênio Singlete/química , Espectrometria de Fluorescência
10.
J Phys Chem Lett ; 11(4): 1228-1238, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31990196

RESUMO

Sonodynamic therapy eliminates cancer cells with reactive oxygen species (ROS) triggered by ultrasound whose energy is spatiotemporally controllable, is safe to human tissues and organs, and penetrates deeply through tissues. Its application, however, is hindered by the scarcity of sonodynamic sensitizers. We herein demonstrate piezoelectric materials as a new source of sonodynamic sensitizers, using few-layer black phosphorus (BP) nanosheet as a model. BP nanosheet exhibited ultrasound-excited cytotoxicity to cancer cells via ROS generation, thereby suppressing tumor growth and metastasis without causing off-target toxicity in tumor-bearing mouse models. The ultrasonic wave introduces mechanical strain to the BP nanosheet, leading to piezoelectric polarization which shifts the conduction band of BP more negative than O2/·O2- while its valence band more positive than H2O/·OH, thereby accelerating the ROS production. This work identifies a new mechanism for discovering sonodynamic sensitizers and suggests BP nanosheet as an excellent sensitizer for tumor sonodynamic therapy.


Assuntos
Nanoestruturas/química , Fósforo/química , Ondas Ultrassônicas , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Camundongos , Nanoestruturas/toxicidade , Neoplasias/patologia , Neoplasias/radioterapia , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo , Transplante Heterólogo , Ultrassonografia
11.
J Photochem Photobiol B ; 204: 111803, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32000112

RESUMO

Infectious diseases constitute a serious problem for human health and life. Although many bacterial and fungal infections can be successfully cured by commonly used antibiotics, a new threat emerges in the form of microbial resistance. For this reason, researchers try to find not only new active pharmaceutical ingredients for conventional antibiotherapy but also try to develop new strategies of microbial inactivation. Photodynamic antimicrobial chemotherapy, which relies on reactive oxygen species generated in situ in the presence of a photosensitizer and with the light of an appropriate wavelength, is one of them. Porphyrazines have been considered as potential photosensitizers for anticancer and antimicrobial photodynamic therapy. In this study, three tribenzoporphyrazines with dendrimeric peripheral substituents were subjected to in vitro antimicrobial photocytotoxicity study. One magnesium(II) tribenzoporphyrazine with peripheral 3,5-bis(3,5-dimethoxybenzyloxy)benzylsulfanyl substituents was synthesized and subjected to physicochemical characterization using NMR, UV-Vis, and mass spectrometry techniques. In photochemical studies this molecule revealed moderate singlet oxygen generation ability (ΦΔDMF = 0.12, ΦΔDMSO = 0.13). The other two magnesium(II) tribenzoporphyrazines applied in the biological study were 4-[3,5-di(hydroxymethyl)phenoxy]butylsulfanyl-substituted tribenzoporphyrazine and 4-[3,5-bis(benzyloxy)benzyloxy]phenyl-substituted tribenzopyrazinoporphyrazine. For the assessment, three microbial strains were chosen: Gram-positive bacteria Staphylococcus aureus ATCC 25923, Gram-negative bacteria Escherichia coli ATCC 25922, and fungal strain Candida albicans ATCC 10231. Very high activity against Staphylococcus aureus at low 10-6 M concentration was recorded for magnesium(II) tribenzoporphyrazines with peripheral 3,5-bis(3,5-dimethoxybenzyloxy)benzylsulfanyl and 4-[3,5-di(hydroxymethyl)phenoxy]butylsulfanyl substituents with calculated log reductions of 4.4 and 4.8, respectively. It is worth noting that magnesium(II) tribenzoporphyrazine with 4-[3,5-di(hydroxymethyl)phenoxy]butylsulfanyl substituents revealed also 3.2 log reduction in bacterial growth at the concentration 10-7 M.


Assuntos
Anti-Infecciosos/farmacologia , Dendrímeros/química , Pirazinas/química , Staphylococcus aureus/efeitos dos fármacos , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Candida albicans/efeitos dos fármacos , Candida albicans/efeitos da radiação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos da radiação , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos da radiação , Luz , Testes de Sensibilidade Microbiana , Pirazinas/síntese química , Pirazinas/farmacologia , Oxigênio Singlete/metabolismo , Staphylococcus aureus/efeitos da radiação
12.
J Med Chem ; 63(4): 1699-1708, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-31967820

RESUMO

Singlet oxygen can severely damage biological tissue, which is exploited in photodynamic therapy (PDT). In PDT, the effective range is limited by the distribution of the photosensitizer (PS) and the illuminated area. However, no distinction is made between healthy and pathological tissue, which can cause undesired damage. This encouraged us to exploit the more acidic pH of cancerous tissue and design pH-controllable singlet oxygen-generating boron-dipyrromethene (BODIPY) dyes. A pH sensitivity of the dyes is achieved by the introduction of an electronically decoupled, photoinduced electron transfer (PET)-capable subunit in meso-position of the BODIPY core. To favor triplet-state formation as required for singlet oxygen generation, iodine substituents were introduced at the chromophore core. The resulting pH-controlled singlet oxygen-generating dyes with pKa values in the physiological range were subsequently assessed regarding their potential as pH-controlled PS for PDT. Using HeLa cells, we could successfully demonstrate markedly different pH-dependent cytotoxicities upon illumination.


Assuntos
Compostos de Boro/farmacologia , Corantes Fluorescentes/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Oxigênio Singlete/metabolismo , Compostos de Boro/síntese química , Compostos de Boro/efeitos da radiação , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Luz , Imagem Óptica , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Nanomedicina Teranóstica
13.
Chemistry ; 26(5): 1091-1102, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31743947

RESUMO

Spin-orbit charge-transfer intersystem crossing (SOCT-ISC) is useful for the preparation of heavy atom-free triplet photosensitisers (PSs). Herein, a series of perylene-Bodipy compact electron donor/acceptor dyads showing efficient SOCT-ISC is prepared. The photophysical properties of the dyads were studied with steady-state and time-resolved spectroscopies. Efficient triplet state formation (quantum yield ΦT =60 %) was observed, with a triplet state lifetime (τT =436 µs) much longer than that accessed with the conventional heavy atom effect (τT =62 µs). The SOCT-ISC mechanism was unambiguously confirmed by direct excitation of the charge transfer (CT) absorption band by using nanosecond transient absorption spectroscopy and time-resolved electron paramagnetic resonance (TREPR) spectroscopy. The factors affecting the SOCT-ISC efficiency include the geometry, the potential energy surface of the torsion, the spin density for the atoms of the linker, solvent polarity, and the energy matching of the 1 CT/3 LE states. Remarkably, these heavy atom-free triplet PSs were demonstrated as a new type of efficient photodynamic therapy (PDT) reagents (phototoxicity, EC50 =75 nm), with a negligible dark toxicity (EC50 =78.1 µm) compared with the conventional heavy atom PSs (dark toxicity, EC50 =6.0 µm, light toxicity, EC50 =4.0 nm). This study provides in-depth understanding of the SOCT-ISC, unveils the design principles of triplet PSs based on SOCT-ISC, and underlines their application as a new generation of potent PDT reagents.


Assuntos
Materiais Biocompatíveis/química , Fármacos Fotossensibilizantes/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Desenho de Fármacos , Espectroscopia de Ressonância de Spin Eletrônica , Elétrons , Células HeLa , Humanos , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/farmacologia , Teoria Quântica , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo , Solventes/química , Marcadores de Spin
14.
J Photochem Photobiol B ; 202: 111703, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31810036

RESUMO

Despite the continuous development of medicine, there is still a lack of effective and fully safe protocols for the treatment of neoplastic diseases. The drug-drug conjugates approach seems to give a chance to obtain more efficient molecules. New alkoxy and metronidazole substituted porphyrins were synthesized. Novel porphyrins were purified by flash column chromatography and characterized using NMR, MS, UV-Vis and HPLC. The Nuclear Magnetic Resonance study was performed to annotate experimentally observed 1H NMR and 13C NMR signals of new compounds. The 2D NMR techniques such as 1H-1H COSY (Correlation Spectroscopy), 1H-13C HSQC (Heteronuclear Single Quantum Correlation) and 1H-13C HMBC (Heteronuclear Multiple Bond Correlation) were used for the structure elucidation of the new compounds. In the range of 250-450 nm of the absorption spectra, the Soret band was observed, whereas the Q band was noted in the range of 500-650 nm. Compounds revealed a fluorescence quantum yield in the range 0.03-0.12. Singlet oxygen generation quantum yields up to 0.54 were determined. Electrochemical properties has also been studied. It has been noticed electropolymerization of compound bearing 5-nitroimidazole substituents. The photodynamic activity of the studied porphyrins against A549 and HEK001/HPV16 cancer cells were examined. The most active against A549 and HEK 001/HPV16 was light-excited trioxanonylporphyrin with the values of IC50 equal to 0.49 µM and 50 nM respectively.


Assuntos
Nitroimidazóis/química , Fármacos Fotossensibilizantes/química , Porfirinas/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Técnicas Eletroquímicas , Humanos , Luz , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/síntese química , Porfirinas/farmacologia , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo
15.
Chemistry ; 26(8): 1789-1799, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31605633

RESUMO

The synthesis of ruthenium(II) phthalocyanines (RuPcs) endowed with one carbohydrate unit-that is, glucose, galactose and mannose-and a dimethylsulfoxide (DMSO) ligand at the two axial coordination sites, respectively, is described. Two series of compounds, one unsubstituted at the periphery, and the other one bearing eight PEG chains at the isoindole meta-positions, have been prepared. The presence of the axial DMSO unit significantly increases the phthalocyanine singlet oxygen quantum yields, related to other comparable RuPcs. The compounds have been evaluated for PDT treatment in bladder cancer cells. In vitro studies have revealed high phototoxicity for RuPcs unsubstituted at their periphery. The phototoxicity of PEG-substituted RuPcs has been considerably improved by repeated light irradiation. The choice of the axial carbohydrate introduced little differences in the cellular uptake for both series of photosensitizers, but the phototoxic effects were considerably higher for compounds bearing mannose units.


Assuntos
Compostos Organometálicos/química , Fármacos Fotossensibilizantes/síntese química , Oxigênio Singlete/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Luz , Compostos Organometálicos/síntese química , Compostos Organometálicos/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Espectrofotometria , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/metabolismo
16.
Chemosphere ; 238: 124687, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31524622

RESUMO

The development of highly efficient and green catalytic oxidation process based on peroxymonosulfate (PMS) activation has been identified to be a significant yet challenging objective in the environmental catalysis field. A simple, environmentally benign and highly effective catalytic oxidation system was innovatively constructed by coupling NaBO2 and PMS for the removal of Acid Red 1. The catalytic mechanism in the NaBO2/PMS system was elucidated by electron paramagnetic resonance (EPR) combined with several radical capture reagents (ascorbic acid, methanol, tert-butyl alcohol, ethanol and l-histidine). The experimental results indicated that singlet oxygen (1O2) severed as the predominant reactive oxygen species (ROS) rather than the HO or during the catalytic oxidation process, at variance with the reported radical pathway in the Co2+/PMS system. Inspiringly, p-benzoquinone (p-BQ) as a trapping agent in most advanced oxidation process could be turned into the positive one in the NaBO2/PMS system, achieving a nearly 3-times enhancement in terms of the rate constant for AR1 removal. More interestingly, sodium chloride (NaCl) presented the same enhancement effect as p-benzoquinone due to generation of hypochlorous acid (HOCl) and more 1O2, which was completely different from the reported. This study develops a highly efficient green oxidation process and opens up a new insight in the remediation of contaminated water.


Assuntos
Boratos/química , Oxirredução , Peróxidos/química , Rodaminas/análise , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Catálise , Oxigênio Singlete/metabolismo
17.
Chem Commun (Camb) ; 56(7): 1078-1081, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31872834

RESUMO

A boron dipyrromethene based photosensitiser substituted with a 1,2,4,5-tetrazine moiety has been prepared of which the photoactivity can be activated upon an inverse-electron-demand Diels-Alder reaction with trans-cyclooctene derivatives. By using a biotin-conjugated trans-cyclooctene to tag the biotin-receptor-positive HeLa cells, this photosensitiser exhibits site-specific activation through cycloaddition, leading to high photocytotoxicity.


Assuntos
Compostos de Boro/farmacologia , Compostos Heterocíclicos com 1 Anel/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/efeitos da radiação , Biotina/análogos & derivados , Biotina/síntese química , Biotina/farmacologia , Compostos de Boro/síntese química , Compostos de Boro/efeitos da radiação , Linhagem Celular Tumoral , Reação de Cicloadição , Ciclo-Octanos/síntese química , Ciclo-Octanos/química , Ciclo-Octanos/farmacologia , Compostos Heterocíclicos com 1 Anel/síntese química , Compostos Heterocíclicos com 1 Anel/efeitos da radiação , Humanos , Luz , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Oxigênio Singlete/metabolismo
18.
Chem Commun (Camb) ; 55(100): 15057-15060, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31777882

RESUMO

We report a novel nanophotosensitizer via one-step covalent assembly of dopamine and genipin. This is the first report unveiling the photodynamic effect of dopamine-based materials. These nanophotosensitizers can also act as pH-responsive drug nanocarriers via a catechol-boronate linkage, thus achieving combined PDT and chemotherapy for highly efficient cancer treatment.


Assuntos
Dopamina/química , Portadores de Fármacos/química , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Ácidos Borônicos/química , Catecóis/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Oxigênio Singlete/metabolismo
19.
J Photochem Photobiol B ; 200: 111647, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31648133

RESUMO

Photoactive materials called photosensitizers can be used for treatment of different types of cancer in combination with light source. In this paper, we have investigated pro-oxidant and antioxidant potentials of four graphene based nanomaterials (graphene oxide-GO, graphene quantum dots-GQDs, carbon quantum dots-CQDs and N-doped carbon quantum dots-N-CQDs) depending on the presence/absence of visible light source. Structural and optical properties of these materials and their potentials for reactive oxygen species generation/quenching are investigated by applying different microscopy and spectroscopy techniques (transmission electron microscopy, FTIR, UV-Vis, photoluminescence, electron paramagnetic resonance). Results show that all types of quantum dots has pro-oxidant and antioxidant potentials whereas GO demonstrated only moderate antioxidant effect. The best free radical scavenger is CQDs sample in the absence of light. CQDs are the best singlet oxygen generator under blue light irradiation as well. To check photo-cytotoxicity of these materials, photo-cytotoxic concentrations of the GO, GQDs, CQDs and N-CQDs were determined for three cellular lines: human rhabdomyosarcoma (RD), cell line derived from human cervix carcinoma Hep2c (HeLa) and fibroblast cell line from murine (L2OB). Cytotoxicity test has indicated that all samples are much less photocytotoxic than cis-diamminedichloroplatinum (cis-DPP). The production method and doping of quantum dots affect the photodynamic activity of tested samples very much.


Assuntos
Antioxidantes/química , Grafite/química , Oxidantes/química , Carbono/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Grafite/toxicidade , Humanos , Microscopia Confocal , Pontos Quânticos/química , Pontos Quânticos/toxicidade , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo
20.
Photochem Photobiol Sci ; 18(11): 2657-2660, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31624823

RESUMO

Mr4511 from Methylobacterium radiotolerans is a 164 amino acid protein built of a flavin mononucleotide (FMN) binding, blue-light responsive LOV (Light, Oxygen, Voltage) core domain plus flanking regions. In contrast to the majority of LOV domains, Mr4511 lacks a tryptophan residue that was previously identified as a major quencher for the FMN triplet state in photosensitizers for singlet oxygen (SO) engineered from these photoreceptors. Here we show that for Mr4511 it is sufficient to only mutate the reactive cysteine responsible for the photocycle (Cys71) in the native protein to generate an efficient SO photosensitizer: both C71S and C71G variants exhibit SO quantum yields of formation, ΦΔ, around 0.2 in air-saturated solutions. Under oxygen saturated conditions, ΦΔ reaches ∼0.5 in deuterated buffer. The introduction of Trp112 in the canonical position for LOV domains dramatically lowers ΦΔ to values comparable to miniSOG, one of the early FMN binding proteins touted as a SO sensitizer. Besides its SO properties, Mr4511 is also exceedingly robust against denaturation with urea and is more photostable than free FMN.


Assuntos
Proteínas de Bactérias/metabolismo , Methylobacterium/metabolismo , Oxigênio Singlete/metabolismo , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Mononucleotídeo de Flavina/química , Mononucleotídeo de Flavina/metabolismo , Polarização de Fluorescência , Mutagênese Sítio-Dirigida , Oxigênio/química , Ligação Proteica , Teoria Quântica , Alinhamento de Sequência , Ureia/química
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