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1.
Mater Sci Eng C Mater Biol Appl ; 109: 110604, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32228929

RESUMO

Self-aggregation of hydrophobic porphyrin-based photosensitizers (PSs) in aqueous biological environment decreases their bioavailability and in vivo therapeutic efficacy, which hampers their clinical use in photodynamic therapy (PDT). In the current study, we explore three new supramolecular systems based of hydrophobic PSs (i.e. 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP) or 5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin (P1COOH)) non-covalently or covalently attached to ß-CD. The two non-covalent solid inclusion complexes (ß-CD)2/mTHPP and [(ß-CD)/P1COOH]4 are prepared by a new co-precipitation@lyophilization combined method and the covalent conjugate ß-CD-P1 by click chemistry. The binding type effect and effectiveness on the disaggregation in aqueous medium and in vitro PDT efficacy against glioblastoma cancer cells of PSs are investigated for the three ß-CD/PS systems. The findings reveal a remarkable improvement of the disaggregation and in vitro PDT activity of these ß-CD/PS systems compared to the free PSs, except for [(ß-CD)/P1COOH]4 inclusion complex caused by J-type self-aggregation of the inclusion complex in tetrameric form. ß-CD-P1 conjugate shows the higher in vitro PDT efficacy compared to the other ß-CD/PS systems. Overall, the results indicate that the disaggregation in aqueous medium and in vitro PDT activity of hydrophobic PSs can be improved by their binding to ß-CD and the covalent binding is the best approach.

2.
Phys Chem Chem Phys ; 22(3): 1222-1241, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31850421

RESUMO

Through the use of tunable vacuum ultraviolet light generated by the DESIRS VUV synchrotron beamline, a jet-stirred reactor was coupled for the first time to an advanced photoionization mass spectrometer based upon a double imaging PhotoElectron PhotoIon COincidence (i2PEPICO) scheme. This new coupling was used to investigate the low-temperature oxidation of n-pentane, a prototype molecule for gasoline or diesel fuels. Experiments were performed under quasi-atmospheric pressure (1.1 bar) with a residence time of 3 s for two equivalence ratios (1/3 and 0.5) with a fuel initial mole fraction of 0.01. The measured time-of-flight mass spectra are in good agreement with those previously obtained with other photoionization mass spectrometers and, like those previous ones, display several m/z peaks for which the related species assignation is ambiguous. This paper shows how the analysis of the coincident mass-tagged Threshold PhotoElectron Spectra (TPES) together with first principle computations, consisting of the determination of the adiabatic ionization energies and the spectra of some products, may assist products' identification. The results mostly confirm those previously obtained by photoionization mass spectrometry and gas chromatography, but also allow a more accurate estimation of the 1-pentene/2-pentene mole fraction ratio. Our data also indicate a higher formation of acetone and methyl ethyl ketone than what is predicted by current models, as well as the presence of products that were not previously taken into account, such as methoxyacetylene, methyl vinyl ketone or furanone. The formation of three, four and five membered ring cyclic ethers is confirmed along with linear ketones: 2- and 3-pentanone. A significant general trend in indicating higher amounts of ketones than are indicated by gas chromatography is noted. Finally, TPES of alkenylhydroperoxides are also provided for the first time and constrains on the isomers identification are provided.

3.
Pharmaceuticals (Basel) ; 12(4)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671658

RESUMO

Photodynamic therapy (PDT) has drawn great interest in recent years mainly due to its low side effects and few drug resistances. Nevertheless, one of the issues of PDT is the need for oxygen to induce a photodynamic effect. Tumours often have low oxygen concentrations, related to the abnormal structure of the microvessels leading to an ineffective blood distribution. Moreover, PDT consumes O2. In order to improve the oxygenation of tumour or decrease hypoxia, different strategies are developed and are described in this review: 1) The use of O2 vehicle; 2) the modification of the tumour microenvironment (TME); 3) combining other therapies with PDT; 4) hypoxia-independent PDT; 5) hypoxia-dependent PDT and 6) fractional PDT.

4.
Environ Technol ; : 1-10, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31180807

RESUMO

This paper addresses the residual toxicity of waters after photocatalysis treatments. The initial waters contain 7 mg L-1 of sulfaquinoxaline (SQX) which is a sulfonamide antibiotic generally recorded inside the water. The contaminated waters are treated by photocatalytic degradation process with bare titania and titania covered with polyaniline (PANI) conducting polymer. The degradation of SQX is conducted at different pH in order to find the optimal condition to obtain SQX concentration relatively equal to zero in the shortest amount of time. This occurs for PANI/TiO2 at pH 12 and TiO2 at pH 4. Toxicity assays (concentration of biomass, pigmentation tests, and cells counting) are undertaken on the microalgae Chlorella vulgaris in order to evaluate the residual toxicity of the 2 treated waters. The toxicity results highlight that the water treated by PANI/TiO2 at pH 12 is the less toxic towards the algae cells. The water processed by bare titania at acidic pH displays unneglectable toxicity towards the algae cells which are larger than the toxicity of the original SQX solution.

5.
Photodiagnosis Photodyn Ther ; 22: 115-126, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29581041

RESUMO

In this study, light-sensitive photosensitizers (Chlorin e6, Ce6) were linked to TiO2 and SiO2 nanoparticles (NPs) in order to develop new kinds of NP-based drug delivery systems for cancer treatment by PDT. TiO2 or SiO2 NPs were modified either by the growth of a polysiloxane layer constituted of two silane reagents ((3-aminopropyl)triethoxysilane (APTES) and tetraethyl orthosilicate (TEOS)) around the core (PEGylated NPs: TiO2@4Si-Ce6-PEG, SiO2@4Si-Ce6-PEG) or simply modified by APTES alone (APTES-modified NPs: TiO2-APTES-Ce6, SiO2-APTES-Ce6). Ce6 was covalently attached onto the modified TiO2 and SiO2 NPs via an amide bond. The absorption profile of the hybridized NPs was extended to the visible region of the light. The physicochemical properties of these NPs were explored by TEM, HR-TEM, XRD, FTIR and zeta potential. The photophysical characteristics including the light absorption, the fluorescence properties and the production reactive oxygen species (1O2 and HO) were also addressed. In vitro experiments on glioblastoma U87 cells were performed to evaluate the photodynamic efficiency of the new hybridized NPs. The cells were exposed to different concentrations of NPs and illuminated (λexc = 652 nm, fluence rate 10 J/cm2). In contrast to the PEGylated NPs, the APTES-modified nanosystems were found to be more efficient for PDT. An interesting photodynamic effect was observed in the case of TiO2-APTES-Ce6 NPs. After illumination, the viability of U87 was decreased by 89% when they were exposed to 200 µg/mL of TiO2-APTES-Ce6 NPs, which corresponds to 0.22 µM of Ce6. The same effect can be obtained with free photosensitizer but using a higher concentration of 10 µM of Ce6.


Assuntos
Nanopartículas/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Dióxido de Silício/química , Titânio/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Microscopia de Fluorescência , Fármacos Fotossensibilizantes/administração & dosagem , Polietilenoglicóis/química , Porfirinas/administração & dosagem , Propilaminas/química , Espécies Reativas de Oxigênio , Silanos/química
6.
Bioorg Med Chem ; 26(3): 688-702, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29338907

RESUMO

Further improvements in Photodynamic therapy (PDT) necessitate that the dye targets more selectively tumour tissues or neovascularization than healthy cells. Different enzymes such as matrix metalloproteinases (MMPs) are overexpressed in tumour areas. Among these MMPs, gelatinases (MMP-2 and MMP-9) and its activator MMP-14 are known to play a key role in tumour angiogenesis and the growth of many cancers such as glioblastoma multiforme (GBM), an aggressive malignant tumour of the brain. These last years, the concept of photodynamic molecular beacons (PMB) became interesting for controlling the photosensitizer's ability to generate singlet oxygen (1O2) close to target biomolecules as MMPs. We report herein novel PMBs triggered by MMP-2 and/or MMP-9 and/or MMP-14, comprising a photosensitizer and a singlet oxygen quencher linked by MMP cleavable peptide linker (H-GRIGFLRTAKGG-OH). First of all, we focused on the synthesis and the photophysical study of different derivatives photosensitizer-peptide. This preliminary work concluded on an influence of the nature and the distance from the peptide, but not of the position of the photosensitizer in these derivatives on the proteolytic enzymatic action. The nature of the quencher used (a blackberry quencher (BBQ-650) or a black hole quencher (BHQ3)) does not influence the enzymatic action. We also studied the influence of an additional PEG spacer. Finally, the synthesis, the singlet oxygen quenching efficiency and the enzymatic activation of these new MMP- cleavable-PMBs were compared.


Assuntos
Peptídeos/química , Fármacos Fotossensibilizantes/química , Sequência de Aminoácidos , Animais , Linhagem Celular Tumoral , Metaloproteinase 14 da Matriz/genética , Metaloproteinase 14 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Peptídeos/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo , Espectrometria de Fluorescência
7.
Bioconjug Chem ; 28(9): 2493-2506, 2017 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-28853858

RESUMO

A novel compound consisting of a cationic porphyrin covalently attached to a derivative of polymyxin B has been synthesized and presents enhanced activity and targeting properties compared to the usual cationic porphyrins recognized as efficient photosensitizers in photodynamic antimicrobial chemotherapy (PACT). A synthesis pathway was established to preserve the bactericidal activity of the peptide. Accordingly, the N-terminal amino acid (l-2,4-diaminobutyric acid) of polymyxin B (PMB) was switched for a cysteine residue. Then, the resulting derivative of PMB was covalently bound to 5-(4-aminophenyl)-10,15,20-tri(4-N-methylpyridyl)-21H,23H-porphyrin using a thiol-maleimide "click" coupling. The peptide-coupled photosensitizer has demonstrated an improved PACT efficiency compared to the cationic porphyrin alone. This enhancement has been observed against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli in particular. Flow cytometry analyses and confocal imaging microscopy demonstrated that the porphyrin-peptide conjugate selectively adhered to the cell walls of either Gram-positive or Gram-negative bacteria, thus justifying the damages induced by singlet oxygen production.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Polimixina B/farmacologia , Porfirinas/farmacologia , Antibacterianos/química , Infecções Bacterianas/tratamento farmacológico , Cátions/química , Cátions/farmacologia , Linhagem Celular , Escherichia coli/efeitos dos fármacos , Humanos , Fármacos Fotossensibilizantes/química , Polimixina B/química , Porfirinas/química , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
8.
Photochem Photobiol ; 93(6): 1439-1448, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28574176

RESUMO

We report the design and synthesis of europium-doped gadolinium oxysulfide nanoscintillators Gd2 O2 S:Eu3+ conjugated with two different photosensitizers (PSs): a zinc chlorin (ZnTPC) and a zinc phtalocyanine (ZnPc) by covalent bonding through a layer of N-(3-trimethoxysilylpropyl)diethylenetriamine (TPDA). These conjugates were designed to be activated under X-ray excitation to allow a photodynamic effect, although this desired outcome was not achieved in this study. The monodispersed nanoparticles of ∼70 nm diameter were pegylated to be stabilized in aqueous suspension. It was shown that the PSs conserved their photophysical properties once conjugated to the nanoscintillator and efficient singlet oxygen was obtained upon photo-irradiation. However, no energy transfer was observed from the nanoscintillator to the photosensitizer neither under photo- nor X-ray irradiation.

9.
J Photochem Photobiol B ; 173: 12-22, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28554072

RESUMO

Polymer-lipid-PEG hybrid nanoparticles were investigated as carriers for the photosensitizer (PS), 5,10,15,20-Tetrakis(4-hydroxy-phenyl)-21H,23H-porphine (pTHPP) for use in photodynamic therapy (PDT). A self-assembled nanoprecipitation technique was used for preparing two types of core polymers poly(d,l-lactide-co-glycolide) (PLGA) and poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) with lipid-PEG as stabilizer. The resulting nanoparticles had an average particle size of 88.5±3.4nm for PLGA and 215.0±6.3nm for PHBV. Both nanoparticles exhibited a core-shell structure under TEM with high zeta potential and loading efficiency. X-ray powder diffraction analysis showed that the encapsulated pTHPP molecules in polymeric nanoparticles no longer had peaks of free pTHPP in the crystalline state. The pTHPP molecules encapsulated inside the polymeric core demonstrated improved photophysical properties in terms of singlet oxygen generation and cellular uptake rate in a FTC-133 human thyroid carcinoma cell line, compared to non-encapsulated pTHPP. The pTHPP-loaded polymer-lipid-PEG nanoparticles showed better in vitro phototoxicity compared to free pTHPP, in both time- and concentration-dependent manners. Overall, this study provides detailed analysis of the photophysical properties of pTHPP molecules when entrapped within either PLGA or PHBV nanoparticle cores, and demonstrates the effectiveness of these systems for delivery of photosensitizers. The two polymeric systems may have different potential benefits, when used with cancer cells. For instance, the pTHPP-loaded PLGA system requires only a short time to show a PDT effect and may be suitable for topical PDT, while the delayed photo-induced cytotoxic effect of the pTHPP-loaded PHBV system may be more suitable for cancer solid tumors. Hence, both pTHPP-encapsulated polymer-lipid-PEG nanoparticles can be considered promising delivery systems for PDT cancer treatment.


Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Porfirinas/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Ácido Láctico/química , Lipídeos/química , Tamanho da Partícula , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Poliésteres/química , Polietilenoglicóis/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros/química , Porfirinas/farmacologia , Oxigênio Singlete/metabolismo , Espectrometria de Fluorescência , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Difração de Raios X
10.
Foods ; 6(1)2017 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-28231085

RESUMO

Carotenoid pigments were extracted and purified from persimmon fruits using accelerated solvent extraction (ASE). Eleven pigments were isolated and five of them were clearly identified as all-trans-violaxanthine, all-trans-lutein, all-trans-zeaxanthin all-trans-cryptoxanthin and all-trans-ß-carotene. Absorption and fluorescence spectra were recorded. To evaluate the potential of ¹O2 quenching of the purified carotenoids, we used a monocarboxylic porphyrin (P1COOH) as the photosensitizer to produce ¹O2. The rate constants of singlet oxygen quenching (Kq) were determined by monitoring the near-infrared (1270 nm) luminescence of ¹O2 produced by photosensitizer excitation. The lifetime of singlet oxygen was measured in the presence of increasing concentrations of carotenoids in hexane. Recorded Kq values show that all-trans-ß-cryptoxanthin, all-trans-ß-carotene, all-trans-lycopene and all-trans-zeaxanthin quench singlet oxygen in hexane efficiently (associated Kq values of 1.6 × 108, 1.3 × 108, 1.1 × 108 and 1.1 × 108 M-1·s-1, respectively). The efficiency of singlet oxygen quenching of ß-cryptoxanthin can thus change the consideration that ß-carotene and lycopene are the most efficient singlet oxygen quenchers acting as catalysts for deactivation of the harmful ¹O2.

11.
Bioorg Med Chem ; 25(1): 1-10, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27769669

RESUMO

Recent researches in photodynamic therapy have focused on novel techniques to enhance tumour targeting of anticancer drugs and photosensitizers. Coupling a photosensitizer with folic acid could allow more effective targeting of folate receptors which are over-expressed on the surface of many tumour cells. In this study, different folic acid-OEG-conjugated photosensitizers were synthesized, characterized and their photophysical properties were evaluated. The introduction of an OEG does not significantly improve the hydrophilicity of the FA-porphyrin. All the FA-targeted photosensitizers present good to very good photophysical properties. The best one appears to be Ce6. Molar extinction coefficient, fluorescence and singlet oxygen quantum yields were determined and were compared to the corresponding photosensitizer alone.


Assuntos
Dietilaminas/química , Ácido Fólico/análogos & derivados , Fármacos Fotossensibilizantes/química , Porfirinas/química , Técnicas de Química Sintética , Dietilaminas/síntese química , Ácido Fólico/síntese química , Humanos , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Porfirinas/síntese química
12.
Eur J Pharm Sci ; 93: 419-30, 2016 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-27575880

RESUMO

Folic acid is a small molecule, also known as vitamin B9. It is an essential compound involved in important biochemical processes. It is widely used as a vector for targeted treatment and diagnosis especially in cancer therapeutics. Nevertheless, not many authors address the problem of folic acid degradation. Several researchers reported their observations concerning its denaturation, but they generally only took into account one parameter (pH, temperature, light or O2etc.). In this review, we will focus on five main parameters (assessed individually or in conjunction with one or several others) that have to be taken into account to avoid the degradation of folic acid: light, temperature, concentration, oxygen and pH, which are the most cited in the literature. Scrupulous bibliographic research enabled us to determine two additional degradation factors that are the influence of singlet oxygen and electron beam on folic acid stability, which are not considered as among the prime factors. Although these two factors are not commonly present as compared to the others, singlet oxygen and electron beams intervene in new therapeutic technologies and must be taken in consideration for further applications such photodynamic or X-rays therapies.


Assuntos
Ácido Fólico/química , Estabilidade de Medicamentos , Ácido Fólico/efeitos da radiação , Concentração de Íons de Hidrogênio , Oxigênio/química , Temperatura , Raios Ultravioleta
13.
PLoS One ; 10(10): e0140645, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26485711

RESUMO

UVA radiation (320-400 nm) is a major environmental agent that can exert its deleterious action on living organisms through absorption of the UVA photons by endogenous or exogenous photosensitizers. This leads to the production of reactive oxygen species (ROS), such as singlet oxygen (1O2) and hydrogen peroxide (H2O2), which in turn can modify reversibly or irreversibly biomolecules, such as lipids, proteins and nucleic acids. We have previously reported that UVA-induced ROS strongly inhibit DNA replication in a dose-dependent manner, but independently of the cell cycle checkpoints activation. Here, we report that the production of 1O2 by UVA radiation leads to a transient inhibition of replication fork velocity, a transient decrease in the dNTP pool, a quickly reversible GSH-dependent oxidation of the RRM1 subunit of ribonucleotide reductase and sustained inhibition of origin firing. The time of recovery post irradiation for each of these events can last from few minutes (reduction of oxidized RRM1) to several hours (replication fork velocity and origin firing). The quenching of 1O2 by sodium azide prevents the delay of DNA replication, the decrease in the dNTP pool and the oxidation of RRM1, while inhibition of Chk1 does not prevent the inhibition of origin firing. Although the molecular mechanism remains elusive, our data demonstrate that the dynamic of replication is altered by UVA photosensitization of vitamins via the production of singlet oxygen.


Assuntos
Replicação do DNA/efeitos da radiação , DNA/efeitos da radiação , Peróxido de Hidrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Oxigênio Singlete/metabolismo , Raios Ultravioleta , Linhagem Celular , DNA/metabolismo , Relação Dose-Resposta à Radiação , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Humanos , Oxirredução
14.
Phys Chem Chem Phys ; 16(28): 14826-33, 2014 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-24921680

RESUMO

The synthesis and photophysical properties of small gold nanoparticles (NPs, AuNP-[Ru-PFF]) surface functionalized by 5-substituted-1,10-phenanthroline-ligand based Ru(II) complexes are described. Luminescence of the grafted and confined Ru(II) complexes is totally quenched on the gold surface. Nonlinear optical properties were determined via Z-scan measurements in the range 600-1300 nm for both the free Ru(II) complex and the related NPs. In the short wavelength range (around 600 nm) the behaviour switches from that of two-photon absorption (2PA) for the complex to saturable absorption for the NPs. 2PA applications such as optical power limiting or two-photon dioxygen sensitization can be anticipated for these nanoplatforms.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Compostos Organometálicos/química , Fenantrolinas/química , Rutênio/química , Estrutura Molecular , Compostos Organometálicos/síntese química , Tamanho da Partícula , Propriedades de Superfície
15.
Photochem Photobiol Sci ; 11(5): 803-11, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22362130

RESUMO

This paper presents energy transfer occurring in small organically modified core-shell nanoparticles (core lanthanide oxide, shell polysiloxane) (diameter < 10 nm) conjugated with photosensitizers designed for photodynamic therapy applications. These nanoparticles covalently encapsulate a photosensitizing PDT drug in different concentrations. Stable dispersions of the nanoparticles were prepared and the photophysical properties of the photosensitizers were studied and compared to those of the photosensitizers in solution. Increasing the photosensitizer concentration in the nanoparticles was not found to cause any changes in the absorption properties while fluorescence and singlet oxygen quantum yields decreased. As a possible explanation, we have suggested that both long distance energy transfer such as FRET and self-quenching could occur into the nanoparticles. A simple "trend" model of this kind of energy transfer complies with results of experiments on steady state fluorescence and singlet oxygen luminescence.


Assuntos
Nanopartículas/química , Fármacos Fotossensibilizantes/química , Portadores de Fármacos/química , Transferência de Energia , Fluorescência , Transferência Ressonante de Energia de Fluorescência , Humanos , Lantânio/química , Luminescência , Modelos Químicos , Neoplasias/tratamento farmacológico , Óxidos/química , Processos Fotoquímicos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Siloxanas/química , Oxigênio Singlete/química , Espectrometria de Fluorescência
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