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1.
Top Curr Chem (Cham) ; 378(2): 21, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32030541

RESUMO

DNA nanostructures hold great promise for various applications due to their remarkable properties, including programmable assembly, nanometric positional precision, and dynamic structural control. The past few decades have seen the development of various kinds of DNA nanostructures that can be employed as useful tools in fields such as chemistry, materials, biology, and medicine. Aptamers are short single-stranded nucleic acids that bind to specific targets with excellent selectivity and high affinity and play critical roles in molecular recognition. Recently, many attempts have been made to integrate aptamers with DNA nanostructures for a range of biological applications. This review starts with an introduction to the features of aptamer-functionalized DNA nanostructures. The discussion then focuses on recent progress (particularly during the last five years) in the applications of these nanostructures in areas such as biosensing, bioimaging, cancer therapy, and biophysics. Finally, challenges involved in the practical application of aptamer-functionalized DNA nanostructures are discussed, and perspectives on future directions for research into and applications of aptamer-functionalized DNA nanostructures are provided.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , DNA/química , Nanoestruturas/química , Técnicas Eletroquímicas , Terapia Genética , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Imagem Óptica/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico
2.
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
3.
J Photochem Photobiol B ; 203: 111763, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31931382

RESUMO

Photodynamic therapy (PDT) is a clinical modality that allows the destruction of tumor cells and microorganisms by reactive oxygen species, formed by the combination of photosensitizer (PS), molecular oxygen and adequate wavelength light. This research, through a clean methodology that involves pressurized liquids extraction (PLE), obtained a highly antimicrobial extract of Tetragonia tetragonoides, which rich in chlorophylls as photosensitizers. The Chlorophylls-based extract (Cbe-PLE) presented pharmacological safety, through the maintenance of cellular viability. In addition, Cbe-PLE showed great efficacy against Staphylococcus aureus, with severe dose-dependent damage to the cell wall of the pathogen. The obtained product has a high potential for the development of photostimulated phytotherapic formulations for clinical applications in localized infections, as a complementary therapeutic alternative to antibiotics.


Assuntos
Aizoaceae/química , Extratos Vegetais/química , Aizoaceae/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Clorofila/química , Clorofila/farmacologia , Luz , Camundongos , Testes de Sensibilidade Microbiana , Nanoestruturas/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Folhas de Planta/química , Folhas de Planta/metabolismo , Caules de Planta/química , Caules de Planta/metabolismo , Staphylococcus aureus/efeitos dos fármacos
4.
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
5.
J Photochem Photobiol B ; 202: 111672, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31778952

RESUMO

In highly proliferating cancer cells oncogenic mutations reprogram the metabolism and increase the production of reactive oxygen species (ROS). Cancer cells prevent ROS accumulation by upregulating antioxidant systems. Here we show that an increase of oxidative stress (ROS and singlet oxygen), generated by photoactivated TMPyP4, results in the upregulation of KRAS and Nrf2, the major regulator of the redox homeostasis. In agreement with a previous observation, the ectopic expression of KRAS G12D or G12 V is found to stimulate Nrf2. This suggests that ROS, KRAS and Nrf2 establish a molecular axis controlling the redox homeostasis in cancer cells. We found that this axis also modulates the function of the NF-kB/Snail/RKIP circuitry, regulating the survival and apoptosis pathways. Our data show that low ROS levels, obtained when Nrf2 is activated by KRAS, results in the upregulation of prosurvival Snail and simultaneous downregulation of proapoptotic RKIP: an expression pattern favouring cell proliferation. By contrast, high ROS levels, obtained when Nrf2 is inhibited by a small molecule (luteolin), favour apoptosis by upregulating proapoptotic RKIP and downregulating prosurvival Snail. The results of this study are useful to design efficient photodynamic therapy (PDT) against cancer. We hypothesize that cancer cells can be sensitized to PDT when the photosensitizer is used in the presence of an inhibitor of Nrf2 (adjuvant). To test this hypothesis, we used luteolin (3',4',5,7-tetrahydroflavone) as Nrf2 inhibitor, since it reduces the expression of Nrf2 and increases intracellular ROS. By means of colony formation and viability assays we found that when Nrf2 is inhibited, PDT shows an increase of efficiency up to 45%.


Assuntos
Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Fator 2 Relacionado a NF-E2/genética , Neoplasias/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Proteína de Ligação a Fosfatidiletanolamina/genética , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/genética , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo
6.
J Photochem Photobiol B ; 202: 111722, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31785445

RESUMO

Nowadays, the study of well-known sensitizers for photodynamic therapy and search for new ones are intensively conducted. In the present work supramolecular organization of crown-ether and phosphoryl-containing phthalocyanines ({Mgcr8Pc, I, and М[R4Pc] (M = Zn2+, R = -OPhP(O)(OH)(OC5H11), II; M = 2H+, R = -OPhP(O)(OH)(OC5H11), III; M = 2H+, -OPhP(O)(OH)2), IIIa}, respectively) was studied in microheterogeneous media. The role of a metal ion of a macrocycle in monomerization of phosphoryl-containing Pc in the presence of water-soluble poly(N-vinylpyrrolidone) was revealed. Some photobiological properties of compound I as possible photosensitizer with respect to human adenocarcinoma cells, HeLa, were analyzed. So, the light and dark cytotoxicity of I (IC50 dose) was 1.83 µÐœ and higher than 25 µÐœ, respectively. The reactive oxygen species (ROS) formation studied with use of fluorescent ROS detector DCFH2 revealed the plateau on the curves of fluorescence intensity vs time after 30 min of irradiation and ROS are almost not produced after the end of irradiation. In HeLa cells, accumulation of compounds I and II as well as fluorescent DCF presence were shown by confocal microscopic images. At concentration of 5 µM, compound I easily penetrates into the cell localizing primarily in the perinuclear region, whereas compound II mainly remains in the periphery of the cells in the fluorescent-active state. The results obtained allow us to continue the study of these interesting compounds.


Assuntos
Éteres de Coroa/química , Indóis/química , Metais/química , Fármacos Fotossensibilizantes/química , Polivinil/química , Pirrolidinas/química , Espécies Reativas de Oxigênio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células HeLa , Humanos , Luz , Microscopia Confocal , Fármacos Fotossensibilizantes/metabolismo , Fármacos Fotossensibilizantes/farmacologia
7.
J Photochem Photobiol B ; 202: 111725, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31790880

RESUMO

Photodynamic therapy (PDT) is an expanding treatment modality due to its minimally invasive localized activity and few adverse effects. This therapy requires photosensitive compounds, which have high sensitivity to light exposure. Thus, in this work, the in vitro antitumor activity of meso-tetra(3- and 4-pyridyl)porphyrins (3-TPyP and 4-TPyP) in metastatic melanoma cell (WM1366 line) and non-tumoral Ovarian lineage Chinese Hamister (CHO) was evaluated using photodynamic process. Cell viability tests, molecular docking, annexin V, confocal microscopy and qRT-PCR were performed. Our results show that both porphyrins inhibited the viability of metastatic melanoma cells when exposed to light and did not alter viability in the dark. In addition, they did not demonstrate cytotoxicity in non-tumor cells. Molecular coupling demonstrated platinum porphyrin affinity for the N-terminal region of APO B-100, LDL receptor, and therefore of the cells under study. Genes such as Caspase 3 and 9, P21, Bax / BCL2, MnSod and GSH showed increased expression. For meta isomer 3-PtTPyP treatment, caspase-9 and caspase-3 expression levels showed a 4.89 and 3.23-fold increase, respectively, while for the para isomer 4-PtTPyP, this change was 3.77 and 12.16-fold, respectively. We also observed an upregulated expression of p21, a protein well-known by its action in cell cycle arrest in a p53-dependent manner. Conclusion: 3-PtTPyP and 4-PtTPyP demonstrated antitumor effect on WM1366 cells, inducing apoptosis and significant alteration of cell cytoskeleton actin. Our work shows that platinum(II) porphyrins may be promising photosensitizers for the treatment of metastatic melanoma by PDT.


Assuntos
Portadores de Fármacos/química , Fármacos Fotossensibilizantes/química , Platina/química , Porfirinas/química , Animais , Apoptose/efeitos dos fármacos , Sítios de Ligação , Células CHO , Caspase 3/genética , Caspase 3/metabolismo , Cátions/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cricetinae , Cricetulus , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Luz , Melanoma/metabolismo , Melanoma/patologia , Simulação de Acoplamento Molecular , Fármacos Fotossensibilizantes/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
8.
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
9.
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
10.
Chem Commun (Camb) ; 56(6): 940-943, 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31850455

RESUMO

Endowing BODIPY PDT agents with the ability to probe lipid droplets is demonstrated to boost their phototoxicity, allowing the efficient use of highly fluorescent dyes (poor ROS sensitizers) as phototoxic agents. Conversely, this fact opens the way to the development of highly bright ROS photosensitizers for performing photodynamic theragnosis (fluorescence bioimaging and photodynamic therapy) from a single simple agent. On the other hand, the noticeable capability of some of the reported dyes to probe lipid droplets in different cell lines under different conditions reveals their use as privileged probes for advancing the study of interesting lipid droplets by fluorescence microscopy.


Assuntos
Compostos de Boro/química , Corantes Fluorescentes/química , Gotículas Lipídicas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Células HeLa , Humanos , Microscopia de Fluorescência , Estrutura Molecular , Imagem Óptica
11.
Chemosphere ; 238: 124552, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31437631

RESUMO

An optical sensor membrane was prepared by electrostatic self-assembled technique for online detection of cadmium ion (II) (Cd(II)). The optical indicator 5,10,15,20-tetrakis(4-N-methylpyridyl) porphyrin p-toluenesulfonate (TMPyP) was adsorbed on a hydrolyzed polyacrylonitrile (PAN) membrane by electrostatic attraction and further immobilized through layer-by-layer deposition of poly(allylamine hydrochloride) (PAH) and poly(sodium 4-styrenesulfonate) (PSS) on the membrane surface. The electrostatic self-assembly of polyelectrolytes on the membrane is influenced by pH and salt concentration of polyelectrolytes. The optical sensor membrane shows distinct color and spectral response to Cd(II) under static and flow-through conditions based on the coordination of TMPyP with Cd(II). A faster detection of Cd(II) is achieved at higher feed concentration of Cd(II) or appropriate lower immobilization capacity of TMPyP on the membrane. The flow-through detection is also influenced by the flow rate; higher flow rate led to faster response to Cd(II) during filtration. Compared with the static process, the flow-through conditions are more conducive to faster analysis of ppb level concentration of Cd(II) (10-3 mg L-1) due to a promoted mass transfer and filtration enrichment. Hence, the development of the optical sensor membrane in this study demonstrated the prospect to make membranes multifunctional with advantages for online chromatic warning in addition to adsorption/rejection of heavy metal ions in the solutions that are treated.


Assuntos
Resinas Acrílicas/química , Técnicas Biossensoriais/métodos , Cádmio/análise , Membranas Artificiais , Fármacos Fotossensibilizantes/química , Polieletrólitos/química , Porfirinas/química , Adsorção , Eletricidade Estática
12.
Niger J Clin Pract ; 22(12): 1654-1661, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31793470

RESUMO

Background: Incomplete eradication of plaque bacteria from the plaque retentive sites and the emerging problem of antibiotic resistance led the scientific community to explore new antimicrobial strategies for improved results and shun antibiotic resistance. Objective: The purpose of this in-vitro study was to evaluate the antimicrobial effect of a novel light based therapy and to assess the susceptibility of oral plaque bacteria to light based technologies with and without photosensitizers. Materials and Methods: Four oral plaque bacterial strains were isolated from the dental plaque sample collected from the patients and exposed to various light based technologies and photodynamic therapy (PDT) with and without photosensitizers. The cultures were analysed for viable colony forming unit (CFU) counts. One-way analysis of variance was used to statistically analyse differences and the Student-Newman-Keuls method to perform multiple comparison procedures. Results: All groups showed remarkable reduction in the CFUs as compared to control group with use of light based technologies and PDT in this study. The difference of antimicrobial effect between all tested groups either with light based technologies and PDT with control group showed significant reduction in CFUs. Conclusions: From the results of this study, we concluded that light based technologies and PDT could be a valuable alternative therapy to mechanical debridement in the prevention of growth and recolonisation of oral plaque bacteria.


Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Placa Dentária/microbiologia , Placa Dentária/terapia , Bolsa Periodontal/microbiologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Bactérias/classificação , Bactérias/isolamento & purificação , Carga Bacteriana/efeitos dos fármacos , Placa Dentária/tratamento farmacológico , Cavidade Pulpar/efeitos dos fármacos , Cavidade Pulpar/microbiologia , Humanos , Técnicas In Vitro , Azul de Metileno/administração & dosagem , Azul de Metileno/uso terapêutico , Bolsa Periodontal/terapia , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/uso terapêutico , Titânio
13.
Zhonghua Yan Ke Za Zhi ; 55(12): 904-910, 2019 Dec 11.
Artigo em Chinês | MEDLINE | ID: mdl-31874503

RESUMO

Objective: To study the safety and efficacy of topography-guided customized excimer laser subepithelial ablation combined with accelerated collagen cross-linking technique in treatment of early keratoconus. Methods: Ninteen patients(20 eyes) (13 males 14 eyes, and 6 females 6 eyes), aged 12 to 44 years (24.7±8.0) were diagnosed as keratoconus by three-dimensional corneal topography and tomography, clinical history and examinations, and classified as KC1~KC3. Based on the classical excimer laser subepithelial keratomileusis (LASEK) method, topography guided laser ablation was performed with an excimer laser system (WaveLight EX500). After laser ablation, the corneal stromal bed was immersed with 0.1% riboflavin for 10 minutes, and then was irradiated by ultraviolet light (Avedro KXL) at 30 mW/cm(2) for 4 minutes. All the patients were followed up for more than 12 months. The uncorrected visual acuity (UCVA), diopter, best corrected visual acuity (BSCVA), corneal topography, central corneal endothelial cell density (ECD), hexagonal cell percentage (HEX), coefficient of variation (CV) and other indicators were observed. For normal distribution variables, Dunnett-t test was used before and after operation, and Wilcoxon test was used for variables with abnormal distribution. And the complications were recorded. Results: There was no loss of BSCVA at 12 months postoperatively, 20% of the eyes had no change of BSCVA, and 15% of the eyes gained 1 line of BSCVA, 15% of the eyes gained 2 lines of BSCVA, 50% of the eyes gained 3 lines and more of BSCVA. There was no significant difference in UCVA, BSCVA, manifest refractive spherical equivalent (MRSE) and the cylinder at 3 months postoperatively (P>0.05). The BSCVA were significantly improved at 6 and 12 months postoperatively compared with those before operation (t=3.095, 3.079, <0.05). Although there was no significant difference in UCVA and MRSE, the cylinder was significantly reduced at 6 and 12 months postoperatively (t=-2.890, -2.435, P<0.05). Apex curvature (Kapex) and mean pupil power (MPP) within 4.5mm of central cornea decreased significantly (Z=-2.903, P<0.01; Z=-2.667, P<0.01). Even though the thinnest corneal thickness decreased from pre-operational (461.9±31.1) µm to post-operational (416.6±27.0) µm (Z=-3.059, P<0.01), the cornea became regular with keratometric asymmetry index of anterior corneal surface decreased (Z=-2.667, P<0.01). The corneal optical quality parameters were improved. There was no significant difference in ECD, HEX and CV at 12 months postoperatively (P>0.05). Twelve months after operation, grade 0, 0.5, 1 and 2 haze were seen on 20%, 55%, 20% and 5% corneas respectively. Conclusions: The topography guided excimer laser ablation combined with accelerated corneal collagen cross linking is safe and effective in treatment of early stage keratoconus. It can significantly improve corneal regularity while preventing keratoconus progression, so as to improve the best corrected visual acuity postoperatively. (Chin J Ophthalmol, 2019, 55: 904-910).


Assuntos
Ceratocone , Terapia a Laser , Adolescente , Adulto , Criança , Colágeno , Córnea , Substância Própria , Topografia da Córnea , Reagentes para Ligações Cruzadas , Feminino , Humanos , Ceratocone/terapia , Masculino , Fármacos Fotossensibilizantes , Raios Ultravioleta , Adulto Jovem
14.
Biomed Khim ; 65(6): 507-512, 2019 Oct.
Artigo em Russo | MEDLINE | ID: mdl-31876521

RESUMO

Cytotoxic and photoinduced activity of chlorine e6 (Ce6) in phospholipid nanoparticles with specific tumor targeting and cell-penetrating peptides was studied in vitro using human fibrosarcoma cells HT-1080. It was shown, that the binding of cell-penetrating peptide R7 - alone or combined with the peptide containing specific targeting motif NGR (Asn-Gly-Arg) - resulted in 3-fold decrease of Ce6 photoinduced activity as compared with that in nanoparticles without peptides (IC50 values were 0.7 µg/ml and 2.1 µg/ml, respectively). The NGR influence was unexpectedly low - less than 20% (IC50 1.7 µg/ml). This suggests the more importance of Ce6 cell penetration in this case, than of NGR-mediated targeting. The effect of inclusion of both peptides on the total cytotoxicity of Ce6 was minimal (10-16 times less than on the specific photoinduced activity). The obtained results - together with earlier shown effects on improvement of the pharmacokinetics of Ce6 in vivo after its embedding into phospholipid nanoparticles - indicate the prospects of using the obtained phospholipid nanoparticles system for photodynamic therapy.


Assuntos
Nanopartículas , Neoplasias/tratamento farmacológico , Peptídeos/farmacologia , Fotoquimioterapia , Porfirinas/química , Linhagem Celular Tumoral , Humanos , Fármacos Fotossensibilizantes
15.
J Biomed Nanotechnol ; 15(12): 2305-2320, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31748013

RESUMO

Verteporfin photodynamic therapy (PDT) has been approved for the treatment of exudative age-related macular degeneration (AMD) for over a decade. However, its extensive application has been impeded by inevitably collateral tissue damage and immediate induction of angiogenesis, in addition to the need of multiple treatments. In order to develop prospective photosensitizers for clinical use, a triphenyl phosphonium-modified cationic liposomal hypocrellin B (TPP cationic LHB) for angiogenic targeting and endothelial internalization was constructed. With optimal PDT parameters, TPP cationic LHB can lead to death of choroid-retinal vascular endothelial cells while cause negligible damage to collateral retinal pigment epithelium cells. This is likely due to the mitochondria targeting and effective intracellular singlet oxygen generation of TPP cationic LHB in vascular endothelial cells. Additionally, in vivo chick chorioallantoic membrane assay indicated the elevated neovessel-targeting ability and photo-induced anti-angiogenic activity of TPP cationic LHB. Furthermore, TPP cationic LHB PDT is able to maintain neovessel occlusion for an extended period of time compared with verteporfin PDT, without inducing significant increased expression of some angiogenic factors, such as vascular endothelial growth factor and integrin αvß3. This study describes a facile strategy that may be useful for developing new-generation photosensitizers to circumvent the limitations of PDT treatment of exudative AMD.


Assuntos
Degeneração Macular , Perileno/análogos & derivados , Fotoquimioterapia , Quinonas/uso terapêutico , Animais , Neovascularização de Coroide , Células Endoteliais , Lipossomos , Degeneração Macular/tratamento farmacológico , Perileno/uso terapêutico , Fármacos Fotossensibilizantes , Estudos Prospectivos , Fator A de Crescimento do Endotélio Vascular
16.
Chem Commun (Camb) ; 55(99): 14898-14901, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31687688

RESUMO

We demonstrate herein an effective cascade reaction for combined photodynamic and starvation therapy in treating breast tumors based on a photosensitizer and CO prodrug decorated NMOF. The PDT-induced ROS can further trigger CO release, and the high antitumor efficiency derived from both 1O2 and CO is well confirmed by in vitro assays and in vivo trials.


Assuntos
Compostos de Boro/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Estruturas Metalorgânicas , Nanoestruturas , Fármacos Fotossensibilizantes/uso terapêutico , Monóxido de Carbono/química , Feminino , Humanos , Manganês/química , Pró-Fármacos/uso terapêutico , Oxigênio Singlete/química
17.
J Photochem Photobiol B ; 200: 111654, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31671373

RESUMO

The Enterococcus faecalis is a microorganism that causes multiple forms of resistance to a wide range of drugs used clinically. aPDT is a technique in which a visible light activates photosensitizer (PS), resulting in generation of reactive oxygen species that kill bacteria unselectively via an oxidative burst. aPDT is an alternative to antibiotics with the advantage of not causing resistance. The search for an alternative treatment of infections caused by E. faecalis, without using antibiotics, is off great clinical importance. The aim of present investigation was to assess the efficacy of using 3.32 ηg/mL of 1,9-dimethylmethylene blue (DMMB) as photosensitizer associated with the use of either Laser (λ660 nm) or LED (λ632 ±â€¯2 nm) using different energy densities (6, 12 and 18 J/cm2) to kill E. faecalis in vitro. Under different experimental conditions, 14 study groups, in triplicate, were used to compare the efficacy of the aPDT carried out with either the laser or LED lights using different energy densities associated to DMMB. The most probable number method (MPN) was used for quantitative analysis. Photodynamic antimicrobial effectiveness was directly proportional to the energy density used, reaching at 18 J/cm2, 99.999998% reduction of the counts of E. faecalis using both light sources. The results of this study showed that the use of 3.32 ηg/mL of DMMB associated with the use 18 J/cm2 of LED light (λ632 ±â€¯2 nm) reduced >7-log counts of planktonic culture of E. faecalis.


Assuntos
Enterococcus faecalis/efeitos dos fármacos , Luz , Azul de Metileno/análogos & derivados , Fármacos Fotossensibilizantes/farmacologia , Animais , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/veterinária , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Azul de Metileno/química , Azul de Metileno/farmacologia , Azul de Metileno/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico
18.
Chem Commun (Camb) ; 55(93): 14081-14084, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31696872

RESUMO

Cholesterol (CHOL) is an indispensable component of liposomes. Incorporation of 7-dehydrocholesterol (7-DHC) instead of CHOL can efficiently enhance the anticancer activity of photosensitizer-encapsulated liposomes upon irradiation, yielding an IC50 value about half of that of CHOL-based controls. The photo-oxidation of 7-DHC into its endoperoxide form by singlet oxygen may account for the enhanced therapeutic effect, realizing an efficient combination of photodynamic therapy (PDT) and photoactivated chemotherapy.


Assuntos
Antineoplásicos/farmacologia , Desidrocolesteróis/farmacologia , Lipossomos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Desidrocolesteróis/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lipossomos/química , Imagem Óptica , Tamanho da Partícula , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo
20.
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
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