Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.018
Filtrar
1.
Int J Nanomedicine ; 14: 7065-7078, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31507320

RESUMO

Background:  Metal-free, water-soluble and highly stable meso-tetra-(4-sulfonatophenyl) porphyrin (TPPS4) has been studied for their singlet oxygen quantum yield. However, TPPS4 suffers from inherent shortcomings. To address these, TPPS4 was conjugated to ternary copper indium sulphide/ zinc sulphide (CuInS2/ZnS) quantum dots (QDs). Purpose:  We herein report for the first time the synthesis of TPPS4-CuInS/ZnS QDs conjugate as an improved photosensitizer. Methods:  Water-soluble TPPS4 was synthesized from tetraphenylporphyrin (TPPH2) after silica-gel purification. The CuInS/ZnS QDs were synthesized by hydrothermal method at a Cu:In ratio of 1:4. The porphyrin-QDs conjugate was formed via the daggling sulfonyl bond of the porphyrin and amine bond of the QDs. The effect of pH on the optical properties of TPPS4 was evaluated. The effect of Zn:Cu + In ratio on the ZnS shell passivation was examined to reduce structural defects on the as-synthesized QDs. Results : Various spectroscopic techniques were used to confirm the successful conversion of the organic TPPH2 to water-soluble TPPS4. The singlet oxygen generation evaluation shows an improved singlet oxygen quantum yield from 0.19 for the porphyrin (TPPS4) alone to 0.69 after conjugation (CuInS/ZnS-TPPS4) with an increase in the reaction rate constant (k (s-1)).


Assuntos
Cobre/química , Índio/química , Porfirinas/síntese química , Porfirinas/farmacologia , Pontos Quânticos/química , Sulfetos/síntese química , Compostos de Zinco/síntese química , Concentração de Íons de Hidrogênio , Fenômenos Ópticos , Fármacos Fotossensibilizantes , Porfirinas/química , Pontos Quânticos/ultraestrutura , Oxigênio Singlete/química , Espectroscopia de Infravermelho com Transformada de Fourier , Sulfetos/química , Temperatura Ambiente , Compostos de Zinco/química
2.
Analyst ; 144(17): 5284-5291, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31372627

RESUMO

5,10,15,20-Tetrakis(4-carboxyl phenyl)porphyrin (Por) modified Co(OH)2 deposited on the surface of GO nanocomposites (Por/Co(OH)2/GO) were prepared and characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and XRD. For the first time, H2TCPP/Co(OH)2/GO is found to have enhanced peroxidase-like activity and catalyze the oxidation of the substrate 3,3,5,5-tetramethylbenzidine (TMB) by hydrogen peroxide (H2O2). Notably, the colorless TMB rapidly transformed into blue oxTMB in just 60 s, which was easily observed visually. The catalytic kinetics of H2TCPP/Co(OH)2/GO is in accord with the Michaelis-Menten equation. The catalytic mechanism of H2TCPP/Co(OH)2/GO nanocomposites is attributed to hydroxyl radicals (˙OH), due to decomposition of H2O2, which is verified by using terephthalic acid as a fluorescent probe. What's more, H2O2 can be detected in a wide linear detection range from 5 to 35 mM with a detection limit of 0.385 mM. Furthermore, based on the excellent peroxidase-like activity of H2TCPP/Co(OH)2/GO, a colorimetric sensor is established to sensitively detect glutathione (GSH) in a linear range from 10 to 300 µM with a low detection limit of 9.5 µM.


Assuntos
Cobalto/química , Grafite/química , Hidróxidos/química , Nanocompostos/química , Peroxidases/química , Porfirinas/química , Benzidinas/química , Materiais Biomiméticos , Técnicas Biossensoriais/métodos , Catálise , Glutationa/análise , Peróxido de Hidrogênio/química , Radical Hidroxila/química , Cinética , Limite de Detecção , Oxirredução , Sensibilidade e Especificidade , Propriedades de Superfície
3.
Chem Asian J ; 14(19): 3320-3328, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31407483

RESUMO

The supramolecular complexation of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) with heptakis(2,3,6-tri-O-methyl)-ß-cyclodextrin (TMCD) has been known to be highly specific in aqueous media. In this study, we have used NMR spectroscopy to reveal that this supramolecular system also works even in biologically crowded media such as serum, blood, and urine. A 13 C-labeled heptakis(2,3,6-tri-O-methyl-13 C)-ß-cyclodextrin (13 C-TMCD) was synthesized and studied using one-dimensional (1D) HMQC spectroscopy in serum and blood. The 1D HMQC spectrum of 13 C-TMCD showed clear signals due to the 2-, 3-, and 6-O13 CH3 groups, whose chemical shifts changed upon addition of TPPS due to quantitative formation of the 13 C-TMCD/TPPS=2/1 inclusion complex in such biological media. The 1 H NMR signals of non-isotope-labeled TPPS included by 13 C-TMCD were detected using the 13 C-filtered ROESY technique. A pharmacokinetic study of 13 C-TMCD and its complex with TPPS was carried out in mice using the 1D HMQC method. The results indicated that (1) 1D HMQC is an effective technique for monitoring the inclusion phenomena of 13 C-labeled cyclodextrin in biological media and (2) the intermolecular interaction between 13 C-TMCD and TPPS is highly selective even in contaminated media like blood, serum, and urine.


Assuntos
Porfirinas/química , beta-Ciclodextrinas/química , Animais , Ânions/química , Isótopos de Carbono/química , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Porfirinas/sangue , Porfirinas/urina , beta-Ciclodextrinas/sangue , beta-Ciclodextrinas/urina
4.
Chemistry ; 25(55): 12801-12809, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31381210

RESUMO

Photodynamic therapy (PDT) is a promising cancer ablation method, but its efficiency is easily affected by several factors, such as the insufficient delivery of photosensitizers, low oxygen levels as well as long distance between singlet oxygen and intended organelles. A multifunctional nanohybrid, named MGAB, consisting of gelatin-coated manganese dioxide and albumin-coated gold nanoclusters, was designed to overcome these issues by improving chlorin e6 (Ce6) delivery and stimulating oxygen production in lysosomes. MGAB were quickly degraded in a high hydrogen peroxide, high protease activity, and low pH microenvironment, which is closely associated with tumor growth. The Ce6-loaded MGAB were picked up by tumor cells through endocytosis, degraded within the lysosomes, and released oxygen and photosensitizers. Upon near-infrared light irradiation, the close proximity of oxygen with photosensitizer within lysosomes enabled the production of cytotoxic singlet oxygen, resulting in more effective PDT.


Assuntos
Portadores de Fármacos/química , Endocitose/fisiologia , Lisossomos/química , Compostos de Manganês/química , Óxidos/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Oxigênio Singlete/metabolismo , Humanos , Raios Infravermelhos , Oxigênio , Fármacos Fotossensibilizantes/farmacocinética , Porfirinas/metabolismo , Oxigênio Singlete/química
5.
Anticancer Res ; 39(8): 4199-4206, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366506

RESUMO

BACKGROUND/AIM: We previously synthesized a glucose-conjugated chlorin compound e6 (G-chlorin e6), and reported that it has very strong antitumor effects. The aim of the present study was to synthesize acetylated glucose-conjugated chlorin (AcN003HP) and evaluate its antitumor effect and excretion. MATERIALS AND METHODS: To evaluate the antitumor effect of AcN003HP, its IC50 was calculated as well as its accumulation in cancer cells was examined by flow cytometry. Confocal microscopy was used to observe the intracellular localization of AcN003HP. The excretion and antitumor effects of AcN003HP were also evaluated in vivo. RESULTS: AcN003HP showed stronger antitumor effects and accumulation into cancer cells compared to talaporfin sodium, a conventional photosensitizer. AcN003HP was localized in the endoplasmic reticulum. In a xenograft tumor mouse model, AcN003HP showed longer excretion time from the body than G-chlorin e6, and photodynamic therapy using AcN003HP showed very strong antitumor effects. CONCLUSION: The safety, improved controllability, and robust antitumor effects suggest AcN003HP as a good next-generation photosensitizer.


Assuntos
Neoplasias Gastrointestinais/terapia , Glucose/administração & dosagem , Fotoquimioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Acetilação/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Retículo Endoplasmático/efeitos dos fármacos , Citometria de Fluxo , Neoplasias Gastrointestinais/patologia , Glucose/síntese química , Glucose/química , Humanos , Camundongos , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Porfirinas/administração & dosagem , Porfirinas/síntese química , Porfirinas/química , Ensaios Antitumorais Modelo de Xenoenxerto
6.
J Phys Chem A ; 123(34): 7470-7485, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31361130

RESUMO

Advances in the utilization of porphyrinoids for photomedicine, catalysis, and artificial photosynthesis require a fundamental understanding of the relationships between their molecular connectivity and resulting electronic structures. Herein, we analyze how the replacement of two pyrrolic Cß═Cß bonds of a porphyrin by two lactone (O═C-O) moieties modulates the ground-state thermodynamic stability and electronic structure of the resulting five possible pyrrole-modified porphyrin isomers. We made these determinations based on density functional theory (DFT) and time-dependent DFT computations of the optical spectra of all regioisomers. We also analyzed the computed magnetically induced currents of their aromatic π-systems. All regioisomers adopt the tautomeric state that maximizes aromaticity, whether or not transannular steric strains are incurred. In all isomers, the O═Cß-Oß bonds were found to support a macrocycle diatropic ring current. We attributed this to the delocalization of nonbonding electrons from the ring oxa- and oxo-atoms into the macrocycle. As a consequence of this delocalization, the dilactone regioisomers are as-or even more-aromatic than their hydroporphyrin congeners. The electronic structures follow different trends for the bacteriochlorin- and isobacteriochlorin-type isomers. The presence of either oxo- or oxa-oxygens conjugated with the macrocyclic π-system was found to be the minimal structural requirement for the regioisomers to exhibit distinct electronic properties. Our computational methods and mechanistic insights provide a basis for the systematic exploration of the physicochemical properties of porphyrinoids as a function of the number, relative orientation, and degree of macrocycle-π-conjugation of ß-substituents, in general, and for dilactone-based porphyrinic chromophores, in particular.


Assuntos
Lactonas/química , Porfirinas/química , Teoria da Densidade Funcional , Isomerismo , Modelos Químicos , Conformação Molecular , Oxazóis/química , Termodinâmica
7.
Chemistry ; 25(51): 11847-11851, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31353639

RESUMO

The controlled self-assembly of porphyrin derivatives (TCPP, tetrakis(4-carboxyphenyl)porphyrin) within Fmoc-protected (Fmoc=9-Fluorenylmethyloxycarbonyl) dipeptide (Fmoc-TL-NH2 ) nanofibers is demonstrated. The biocatalytic co-assembly in aqueous medium generated an energy transfer hydrogel. Depending on the concentrations of porphyrin used, the resulting nanofibrous gels show two distinct regions of self-assembly behavior that is, integration of TCPP into nanostructures to produce two-component co-assembly fibers, or heterogeneous self-aggregation of TCPP within the self-assembled matrix observed at higher concentrations. The mode of assembly directly impacts on the energy transfer efficiency of these nanostructures. These results show that reversible biocatalytic co-assembly of structural and functional components enables fine-tuning of peptide/porphyrin energy transfer nanostructures.


Assuntos
Dipeptídeos/química , Peptídeos/química , Porfirinas/química , Biocatálise , Transferência de Energia , Hidrogéis/química , Nanofibras/química , Nanoestruturas/química
8.
J Photochem Photobiol B ; 197: 111548, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31288120

RESUMO

The visible light combined with photosensitizers (PSs) is exploited in both antitumoral and antimicrobial fields inducing a photo-oxidative stress within the target cells. Among the different PSs, porphyrins belong to the family of the most promising compounds to be used in clinical photodynamic applications. Although in the last years many porphyrins have been synthesised and tested, only a few reports concern the in vitro effects of the 5,15-diarylporphyrins. In this work, the activity of four 5,15-diarylporphyrins (compounds 7-10), bearing alkoxy-linked pyridinium appendixes, have been tested on cancer cell lines and against bacterial cultures. Among the synthetized PSs, compounds 7 and 9 are not symmetrically substituted porphyrins showing one cationic charge tethered at the end of one 4C or 8C carbon chains, respectively. On the other hand, compounds 8 and 10 are symmetrically substituted and show two chains of C4 and C8 carbons featuring a cationic charge at the end of both chains. The dicationic 8 and 10 were more hydrophilic than monocationic 7 and 9, outlining that the presence of two pyridinium salts have a higher impact on the solubility in the aqueous phase than the lipophilic effect exerted by the length of the alkyl chains. Furthermore, these four PSs showed a similar rate of photobleaching, irrespective of the length and number of chains and the number of positive charges. Among the eukaryotic cell lines, the SKOV3 cells were particularly sensitive to the photodynamic activity of all the tested diarylporphyrins, while the HCT116 cells were found more sensitive to PSs bearing C4 chain (7 and 8), regardless the number of cationic charges. The photo-induced killing effect of these porphyrins was also tested against two different bacterial cultures. As expected, the Gram positive Bacillus subtilis was more sensitive than the Gram negative Escherichia coli, and the dicationic porphyrin 8, bearing two C4 chains, was the most efficient on both microorganisms. In conclusion, the new compound 8 seems to be an optimal candidate to deepen as versatile anticancer and antibacterial photosensitizer.


Assuntos
Antibacterianos/química , Antineoplásicos/química , Fármacos Fotossensibilizantes/química , Porfirinas/química , Antibacterianos/síntese química , Antibacterianos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Cátions/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Luz , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/síntese química , Porfirinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo
9.
Chem Commun (Camb) ; 55(65): 9590-9605, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31334709

RESUMO

The study of artificial receptor molecules with the intention to mimic enzyme-substrate binding processes and catalysis in nature has always been a traditional area of research in supramolecular chemistry. Along this line, our group has developed a family of porphyrin cage compounds based on glycoluril and employed these in host-guest binding studies, as components of allosterically controlled self-assembled processes, in which structural changes in the cage upon complexation of a guest or a ligand change binding equilibria, and as enzyme mimics in supramolecular catalysis. In a recently started research program aimed at developing a new molecular approach to long-term data storage, porphyrin cage compounds are studied as molecular machines to encode information into synthetic polymer chains. In this Feature Article we will give an overview of the above aspects of our porphyrin cage compounds and place them in the context of related systems reported in the literature.


Assuntos
Alquinos/química , Materiais Biomiméticos/química , Imidazóis/química , Porfirinas/química , Receptores Artificiais/química , Materiais Biomiméticos/síntese química , Catálise , Imidazóis/síntese química , Ligantes , Metaloporfirinas/síntese química , Metaloporfirinas/química , Nanotecnologia/métodos , Porfirinas/síntese química , Receptores Artificiais/síntese química , Estereoisomerismo , Termodinâmica
10.
Photochem Photobiol Sci ; 18(8): 1910-1922, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31328761

RESUMO

New porphyrin/4-oxoquinoline conjugates were synthesized from the Heck coupling reaction of a ß-brominated porphyrin with 1-allyl-4-oxoquinoline derivatives, followed by demetallation and deprotection affording the promising photosensitizers 9a-e. Singlet oxygen studies have demonstrated that all the porphyrin/4-oxoquinoline conjugates 9a-e were capable of producing cytotoxic species and found to be excellent photosensitizing agents in the inactivation of S. aureus by the antimicrobial photodynamic therapy (aPDT) protocol.


Assuntos
4-Quinolonas/farmacologia , Antibacterianos/farmacologia , Fotoquimioterapia , Porfirinas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , 4-Quinolonas/química , Antibacterianos/síntese química , Antibacterianos/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Porfirinas/química
11.
Chem Soc Rev ; 48(16): 4387-4400, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31237282

RESUMO

Bioinspired nanostructures can be the ideal functional smart materials to bridge the fundamental biology, biomedicine and nanobiotechnology fields. Among them, short peptides are among the most preferred building blocks as they can self-assemble to form versatile supramolecular architectures displaying unique physical and chemical properties, including intriguing optical features. Herein, we discuss the progress made over the past few decades in the design and characterization of optical short peptide nanomaterials, focusing on their intrinsic photoluminescent and waveguiding performances, along with the diverse modulation strategies. We review the complicated optical properties and the advanced applications of photoactive short peptide self-assemblies, including photocatalysis, as well as photothermal and photodynamic therapy. The diverse advantages of photoactive short peptide self-assemblies, such as eco-friendliness, morphological and functional flexibility, and ease of preparation and modification, endow them with the capability to potentially serve as next-generation, bio-organic optical materials, allowing the bridging of the optics world and the nanobiotechnology field.


Assuntos
Nanoestruturas/química , Peptídeos/química , Catálise , Glucose/análise , Humanos , Hidrogéis/química , Luz , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Porfirinas/química , Porfirinas/uso terapêutico
12.
Photochem Photobiol Sci ; 18(7): 1700-1708, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31214675

RESUMO

The ever growing world-population poses challenges concerning the need for more food free of pesticide residues. The most common means to control plant pathogens is through the application of pesticides, which raises concerns over safety for humans and the environment. Recently, Photodynamic Inactivation (PDI) of microorganisms using natural photosensitizers has shown itself to be a powerful tool to combat bacteria and fungi. This study investigates the efficacy of PDI against the Gram(+) bacterial plant pathogen Rhodococcus fascians and Gram(-) Xanthomonas axonopodis and Erwinia amylovora using two chlorin e6 derivatives as photosensitizers: anionic sodium magnesium chlorophyllin (Chl, approved as food additive E140) in combination with cell wall permeabilizing agents (Na2EDTA or Polyaspartic acid sodium salt (PA)) and B17-0024, a mixture of chlorin e6 derivatives with cationic moieties at physiological pH. Both photosensitizers show excellent efficacy against R. fascians, whereby B17-0024 is phototoxic at a one order of magnitude lower concentration than Chl (10 µM B17-0024: relative inactivation (r.i.) >7.5 × 106, 100 µM Chl: r.i. 2.2 × 106, illumination with 26.6 J cm-2, 395 nm). The phototreatment of Gram(-) bacteria with Chl requires the obligatory use of cell wall permeabilizing agents like Na2EDTA (X. axonopodis) or PA (E. amylovora) to induce significant killing (more than 7 log units at 100 µM). On the other hand, B17-0024 proves to be a highly effective photosensitizer inducing bacterial inactivation at very low concentrations (10 µM for R. fascians and X. axonopodis, 100 µM for E. amylovora) without additives. In summary, PDI using both the natural photosensitizer Chl in combination with cell wall permeabilizing agents is effective and environmentally friendly. As an alternative, B17-0024 is highly photoactive against all model strains tested - even without cell wall permeabilizing agents. The photodynamic approach based on chlorin e6 derivatives should add to the growers' toolbox as a preferred alternative for the control of phytopathogens.


Assuntos
Produtos Agrícolas/microbiologia , Erwinia amylovora/efeitos da radiação , Luz , Rhodococcus/efeitos da radiação , Xanthomonas axonopodis/efeitos da radiação , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Erwinia amylovora/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Porfirinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Rhodococcus/efeitos dos fármacos , Xanthomonas axonopodis/efeitos dos fármacos
13.
Curr Med Chem ; 26(24): 4506-4536, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31119997

RESUMO

Traditionally, natural medicines have been administered as plant extracts, which are composed of a mixture of molecules. The individual molecular species in this mixture may or may not contribute to the overall medicinal effects and some may even oppose the beneficial activity of others. To better control therapeutic effects, studies that characterized specific molecules and describe their individual activity that have been performed over the past decades. These studies appear to underline that natural products are particularly effective as antioxidants and anti-inflammatory agents. In this systematic review we aimed to identify potent anti-inflammatory natural products and relate their efficacy to their chemical structure and physicochemical properties. To identify these compounds, we performed a comprehensive literature search to find those studies, in which a dose-response description and a positive control reference compound was used to benchmark the observed activity. Of the analyzed papers, 7% of initially selected studies met these requirements and were subjected to further analysis. This analysis revealed that most selected natural products indeed appeared to possess anti-inflammatory activities, in particular anti-oxidative properties. In addition, 14% of the natural products outperformed the remaining natural products in all tested assays and are attractive candidates as new anti-inflammatory agents.


Assuntos
Anti-Inflamatórios/química , Produtos Biológicos/química , Animais , Anti-Inflamatórios/uso terapêutico , Produtos Biológicos/uso terapêutico , Cumarínicos/química , Cumarínicos/uso terapêutico , Edema/tratamento farmacológico , Edema/patologia , Plantas Medicinais/química , Plantas Medicinais/metabolismo , Porfirinas/química , Porfirinas/uso terapêutico , Relação Estrutura-Atividade
14.
Nanomedicine (Lond) ; 14(10): 1343-1365, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31084393

RESUMO

Nanoscale metal-organic frameworks (MOFs) have been widely used as controlled drug delivery vehicles and cancer therapy agents due to their intrinsic superior properties. Scientists have made remarkable achievements in the field of nanomedicine by using the MOFs and MOF-based multifunctional nanomaterials due to the easy synthesis into nanoscale and functionalization. In this review, we highlight the recent progress of nanoscale MOFs as drug delivery vehicles for cancer theranostics. We divide the discussion into three parts. The first and second parts focus on the drug delivery of unmodified MOF and modified MOFs, respectively, while the third part focuses on porphyrin MOFs as photosensitizers for photodynamic therapy. Finally, we conclude by identifying areas of research that we believe will propel the translation and application of MOFs.


Assuntos
Antineoplásicos/química , Portadores de Fármacos/química , Estruturas Metalorgânicas/química , Nanopartículas/química , Animais , Liberação Controlada de Fármacos , Humanos , Nanomedicina , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Porfirinas/química
15.
Chem Commun (Camb) ; 55(44): 6241-6244, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31086880

RESUMO

Glutathione (GSH) in tumors consumes 1O2 and seriously inhibits the PDT effect. MnO2-coated porphyrin metal-organic frameworks are developed to realize the oxidation of GSH by MnO2 for enhanced PDT, activated MR imaging, and controllable release of DOX as magnetic resonance imaging guided drug-PDT dual-therapy.


Assuntos
Glutationa/metabolismo , Imagem por Ressonância Magnética/métodos , Compostos de Manganês/química , Estruturas Metalorgânicas/química , Óxidos/química , Fotoquimioterapia/métodos , Porfirinas/química , Terapia Combinada
16.
Chem Commun (Camb) ; 55(44): 6269-6272, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31086908

RESUMO

Porphyrin-based covalent organic polymer nanoparticles were synthesized via a Schiff base reaction at room temperature. The resulting product showed a good photodynamic effect and a high photothermal conversion efficiency (34.88%). Both in vitro and in vivo experiments demonstrated the enhanced antitumor efficacy via synergistic photodynamic and photothermal therapy.


Assuntos
Antineoplásicos/farmacologia , Nanopartículas , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fototerapia/métodos , Polietilenoglicóis/farmacologia , Porfirinas/farmacologia , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Células HeLa , Humanos , Camundongos , Microscopia Eletrônica de Varredura , Fármacos Fotossensibilizantes/química , Porfirinas/química , Difração de Pó , Bases de Schiff/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Cell Physiol Biochem ; 52(6): 1325-1338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31050281

RESUMO

BACKGROUND/AIMS: Atherosclerosis is a chronic inflammatory cardiovascular disease. Macrophages are major components of atherosclerotic plaques and play a key role in the development of atherosclerosis by secreting a variety of pro-inflammatory factors. Our previous studies have confirmed that upconversion nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) mediated photodynamic therapy (PDT) can promote cholesterol efflux and induce apoptosis in THP-1 macrophages. In this study, we investigated whether reactive oxygen species (ROS) generated by UCNPs-Ce6-mediated PDT can induce autophagy to inhibit the expression of pro-inflammatory factor in M1 peritoneal macrophages. METHODS: Peritoneal macrophages were collected from C57/BL6 mice injected with 3% thioglycollate broth medium and induced by lipopolysaccharides and interferon-γ. Intracellular ROS production was assessed by 2'-7'-dichloroflorescein diacetate and flow cytometry. Autophagy was assayed by western blot, transmission electron microscopy and immunofluorescence. Pro-inflammatory cytokines were detected by enzyme-linked immunosorbent assay and western blot. RESULTS: Model M1 peritoneal macrophages were established after 24 h induction. Protein expression levels of LC3 II and Beclin1, and degradation of p62 increased and peaked at 2 h in the PDT group. Meanwhile, levels of inflammatory cytokines iNOS, IL-12, and TNF-α markedly decreased after PDT. The increase in autophagy levels and decrease in pro-inflammatory cytokines were significantly inhibited by 3-methyladenine. Furthermore, ROS generated by UCNPs- Ce6 mediated PDT activated autophagy. The expression of autophagy related-protein and inflammatory cytokines iNOS, IL-12, and TNF-α were inhibited by the ROS inhibitor N-acetyl cysteine. CONCLUSION: ROS generated by UCNPs-Ce6-mediated PDT activated autophagy and inhibited the expression of pro-inflammatory factors of M1 peritoneal macrophage via the PI3K/AKT/mTOR signaling pathway.


Assuntos
Autofagia/efeitos dos fármacos , Nanopartículas Metálicas/química , Porfirinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Proteína Beclina-1/metabolismo , Interleucina-12/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fotoquimioterapia , Porfirinas/química , Porfirinas/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
18.
J Photochem Photobiol B ; 195: 39-50, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31075653

RESUMO

Photodynamic therapy (PDT) of cancer uses photosensitizers (PS), a light source and oxygen to generate high levels of reactive oxygen species (ROS), that exert a cytotoxic action on tumor cells. Recently, it has been shown that mixed non-symmetrical diaryl porphyrins, with two different pendants, are more photodynamically active than symmetrical diaryl porphyrins. In the present study, we investigate the in vitro photodynamic effects of four novel non-symmetrical diaryl porphyrins, two of which bear one pentafluoro-phenyl and one bromo-alkyl (apolar) pendant, whereas the two others bear one pentafluoro-phenyl and one cationic pyridine pendant. The four compounds were tested in a small panel of human cancer cell lines, and their photodynamic activities were compared with that of m-THPC (Foscan), currently the most successful PS approved for clinical use in cancer PDT. The results of the cytotoxicity studies indicate that the two molecules bearing the cationic pendant are more potent in vitro than those with the apolar pendant, and that they are as potent as Foscan. To gain further insights into the mechanism of PS-induced phototoxicity, induction of apoptotic, autophagic and necrotic cell death, and generation of reactive oxygen species (ROS) were evaluated in cancer cells following exposure to the PSs and irradiation. The effect of the PSs on the migratory activity of the cells was also assessed. The data obtained from this work support a greater potency of diaryl porphyrins with a positive charge in inducing cell death, as compared to those with the bromo-alkyl pendant; most importantly, some of these novel compounds exhibit features that might make them superior to the clinically approved PS Foscan.


Assuntos
Fármacos Fotossensibilizantes/síntese química , Porfirinas/química , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/efeitos da radiação , Humanos , Luz , Neoplasias/tratamento farmacológico , Fotodegradação , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
19.
Phys Chem Chem Phys ; 21(19): 10095-10104, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31062770

RESUMO

The first step in the biodegradation of imidazolium-based ionic liquids involves the insertion of the -OH group into the alkyl side chain, and it is believed to be triggered by cytochrome P450. However, at present, there is a lack of fundamental understanding of why the hydroxylation process is observed only for longer alkyl chain analogues. As the initial step of the hydroxylation reaction involves the ionic liquid binding to Fe-porphyrin (FeP) - the catalytic center of cytochrome P450, the orientation of ionic liquids presented to FeP is expected to play a crucial role in eventual hydroxylation of the alkyl side chain. In order to elucidate the chain-length dependent binding preferences exhibited by the homologous series of 1-n-alkyl-3-methylimidazolium (n = 2, 4, 6, 8, and 10) [Cnmim]+ cations, a quantum mechanical treatment of the cations in the presence of free base porphyrin (FBP) and FeP is carried out at the B3LYP-D2 and M06 levels. The binding energy of different complexes with FBP and FeP is investigated by considering three vastly different starting relative orientations of the cations with respect to FBP and FeP: tail down, tail up, and interplanar. Our calculations of binding energies reveal that the cation orientations initiated from the tail down conformations (alkyl chain facing the porphyrin molecules) are progressively destabilized as the alkyl chain length increases. The decomposition of the binding energies into various energetic contributions shows that the interaction energy between the cations and porphyrin molecules varies with the cation geometries presented to porphyrin molecules and is the primary determinant of the magnitude of the binding energies. We further demonstrate that the propensity of the cation-FeP complexes to acquire an electron, the next step in the hydroxylation reaction cycle upon substrate binding, is favored independent of the cations and conformations, suggesting that this step is not the reason for the low biodegradability of short alkyl chain bearing cations. Furthermore, the weaker binding of the ionic liquid to FeP is anticipated to facilitate dioxygen binding to FeP, the step following the electron transfer reaction. Overall, the results of the present calculations indicate that the destabilization of the tail down conformations relative to the other two conformations correlates with the experimental results of the chain length-dependent biodegradation of imidazolium-based ionic liquids.


Assuntos
Teoria da Densidade Funcional , Imidazóis/química , Líquidos Iônicos/química , Porfirinas/química , Sítios de Ligação , Cátions/química , Conformação Molecular
20.
Sensors (Basel) ; 19(9)2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31052151

RESUMO

The odor information produced in Saccharomyces cerevisiae culture is one of the important characteristics of yeast growth status. This work innovatively presents the quantitative monitoring of cell concentration during the yeast culture process using a homemade color sensor. First, a color sensor array, which could visually represent the odor changes produced during the yeast culture process, was developed using eleven porphyrins and one pH indicator. Second, odor information of the culture substrate was obtained during the process using the homemade color sensor. Next, color components, which came from different color sensitive spots, were extracted first and then optimized using the ant colony optimization (ACO) algorithm. Finally, the back propagation neural network (BPNN) model was developed using the optimized feature color components for quantitative monitoring of cell concentration. Results demonstrated that BPNN models, which were developed using two color components from FTPPFeCl (component B) and MTPPTE (component B), can obtain better results on the basis of both the comprehensive consideration of the model performance and the economic benefit. In the validation set, the average of determination coefficient R P 2 was 0.8837 and the variance was 0.0725, while the average of root mean square error of prediction (RMSEP) was 1.0033 and the variance was 0.1452. The overall results sufficiently demonstrate that the optimized sensor array can satisfy the monitoring accuracy and stability of the cell concentration in the process of yeast culture.


Assuntos
Técnicas Biossensoriais , Técnicas de Cultura de Células , Rastreamento de Células , Saccharomyces cerevisiae/isolamento & purificação , Algoritmos , Cor , Concentração de Íons de Hidrogênio , Redes Neurais (Computação) , Porfirinas/química , Saccharomyces cerevisiae/crescimento & desenvolvimento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA