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Possibility for a full optical determination of photodynamic therapy outcome

VOLLET-FILHO, J. D.; MENEZES, P. F. C.; MORIYAMA, L. T.; GRECCO, C.; SIBATA, C.; ALLISON, R. R.; SILVA, O. Jr. Castro e; BAGNATO, V. S.
Fonte: AMER INST PHYSICS Publicador: AMER INST PHYSICS
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
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The efficacy of photodynamic therapy (PDT) depends on a variety of parameters: concentration of the photosensitizer at the time of treatment, light wavelength, fluence, fluence rate, availability of oxygen within the illuminated volume, and light distribution in the tissue. Dosimetry in PDT requires the congregation of adequate amounts of light, drug, and tissue oxygen. The adequate dosimetry should be able to predict the extension of the tissue damage. Photosensitizer photobleaching rate depends on the availability of molecular oxygen in the tissue. Based on photosensitizers photobleaching models, high photobleaching has to be associated with high production of singlet oxygen and therefore with higher photodynamic action, resulting in a greater depth of necrosis. The purpose of this work is to show a possible correlation between depth of necrosis and the in vivo photosensitizer (in this case, Photogem (R)) photodegradation during PDT. Such correlation allows possibilities for the development of a real time evaluation of the photodynamic action during PDT application. Experiments were performed in a range of fluence (0-450 J/cm(2)) at a constant fluence rate of 250 mW/cm(2) and applying different illumination times (0-1800 s) to achieve the desired fluence. A quantity was defined (psi) as the product of fluorescence ratio (related to the photosensitizer degradation at the surface) and the observed depth of necrosis. The correlation between depth of necrosis and surface fluorescence signal is expressed in psi and could allow...

Phototransformation of hematoporphyrin in aqueous solution: Anomalous behavior at low oxygen concentration

PRATAVIEIRA, S.; SANTOS, P. L. A.; MENEZES, P. F. C.; KURACHI, Cristina; SIBATA, C. H.; JARVI, M. T.; WILSON, B. C.; BAGNATO, Vanderlei Salvador
Fonte: MAIK NAUKA/INTERPERIODICA/SPRINGER Publicador: MAIK NAUKA/INTERPERIODICA/SPRINGER
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
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The photoactivation of a photosensitizer is the initial step in photodynamic therapy (PDT) where photochemical reactions result in the production of reactive oxygen species and eventually cell death. In addition to oxidizing biomolecules, some of these photochemical reactions lead to photosensitizer degradation at a rate dependent on the oxygen concentration among other factors. We investigated photodegradation of Photogem A (R) (28 mu M), a hematoporphyrin derivative, at different oxygen concentrations (9.4 to 625.0 mu M) in aqueous solution. The degradation was monitored by fluorescence spectroscopy. The degradation rate (M/s) increases as the oxygen concentration increases when the molar ratio of oxygen to PhotogemA (R) is greater than 1. At lower oxygen concentrations (< 25 mu M) an inversion of this behavior was observed. The data do not fit a simple kinetic model of first-order dependence on oxygen concentration. This inversion of the degradation rate at low oxygen concentration has not previously been demonstrated and highlights the relationship between photosensitizer and oxygen concentrations in determining the photobleaching mechanism(s). The findings demonstrate that current models for photobleaching are insufficient to explain completely the effects at low oxygen concentration.; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); CEPID; FAPESP; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); CAPES; Canadian Cancer Society/NCIC; Canadian Cancer Society/NCIC

Analysis of the combined effect of lasers of different wavelengths for PDT outcome using 600, 630, and 660 nm

ATIF, M.; FAKHAR-E-ALAM, M.; SABINO, L. G.; IKRAM, M.; ARAUJO, M. T. de; KURACHI, Cristina; BAGNATO, Vanderlei Salvador; ALSALHI, M. S.
Fonte: WILEY-BLACKWELL Publicador: WILEY-BLACKWELL
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
27.20222%
We investigated the effects of photodynamic therapy (PDT) outcome when combining three laser systems that produce light in three different wavelengths (600, 630, and 660 nm). Cooperative as well as independent effects can be observed. We compared the results of the combined wavelengths of light with the effect of single laser for the excitation of the photosensitizer. In the current experiment, the used photosensitizer was Photogem (R) (1.5 mg/kg). Combining two wavelengths for PDT, their cumulative dose and different penetrability may change the overall effect of the fluence of light, which can be effective for increasing the depth of necrosis. This evaluation was performed by comparing the depth and specific aspect of necrosis obtained by using single and dual wavelengths for irradiation of healthy liver of male Wistar rats. We used 15 animals and divided them in five groups of three animals. First, Photogem (R) was administered; follow by measurement of the fluorescence spectrum of the liver before PDT to confirm the level of accumulation of photosensitizer in the tissue. After that, an area of 1 cm(2) of the liver was illuminated using different laser combinations. Qualitative analysis of the necrosis was carried out through histological and morphological study. [GRAPHICS] (a) - microscopic images of rat liver cells...

Non-homogeneous liver distribution of photosensitizer and its consequence for photodynamic therapy outcome

VOLLET-FILHO, Jose Dirceu; CARACANHAS, Monica Andrioli; GRECCO, Clovis; FERREIRA, Juliana; KURACHI, Cristina; BAGNATO, Vanderlei Salvador
Fonte: ELSEVIER SCIENCE BV Publicador: ELSEVIER SCIENCE BV
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
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Background: Photodynamic therapy is mainly used for treatment of malignant lesions, and is based on selective location of a photosensitizer in the tumor tissue, followed by light at wavelengths matching the photosensitizer absorption spectrum. In molecular oxygen presence, reactive oxygen species are generated, inducing cells to die. One of the limitations of photodynamic therapy is the variability of photosensitizer concentration observed in systemically photosensitized tissues, mainly due to differences of the tissue architecture, cell lines, and pharmacokinetics. This study aim was to demonstrate the spatial distribution of a hematoporphyrin derivative, Photogem(R), in the healthy liver tissue of Wistar rats via fluorescence spectroscopy, and to understand its implications on photodynamic response. Methods: Fifteen male Wistar rats were intravenously photosensitized with 1.5 mg/kg body weight of Photogem(R). Laser-induced fluorescence spectroscopy at 532nm-excitation was performed on ex vivo liver slices. The influence of photosensitizer surface distribution detected by fluorescence and the induced depth of necrosis were investigated in five animals. Results: Photosensitizer distribution on rat liver showed to be greatly non-homogeneous. This may affect photodynamic therapy response as shown in the results of depth of necrosis. Conclusions: As a consequence of these results...

Estudos sinérgicos de fármacos fotossensibilizadores utilizados na terapia fotodinâmica e fluidos magnéticos utilizados em hipertermia celular; Studies synergic of photosensitizer drug used in the Photodynamic therapy and magnetic fluids used in cellular Hyperthermia

Oliveira, Daniela Manfrim de
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 04/08/2006 PT
Relevância na Pesquisa
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O principal interesse neste estudo foi a proposição de uma nova classe de material que permite a ação combinada da Terapia Fotodinâmica (TFD) e da Hipertermia (HPT), projetadas para trabalhar sinergicamente, que possa levar a uma considerável regressão de tumores neoplásicos após mínimas doses de dissipação de calor e/ou fotossensitização luminosa. Esta nova classe de material se baseia em um lipossoma de longo tempo de circulação associado ao fármaco fotossensibilizador (FS) zinco ftalocianina (ZnPC), na presença de fluido magnético (FM) constituído por nanopartículas de ferrita de cobalto (CoFe2O4) recobertas com ácido cítrico. As propriedades fotofísicas (em meio orgânico e em meio lipossomal) e os estudos fotobiológicos em células da linhagem B-16 foram desenvolvidos para avaliar as propriedades da ZnPC na ausência e na presença de FM. As propriedades fotofísicas da ZnPC em meio orgânico e lipossomal, na ausência e na presença de FM, foram realizadas empregando-se técnicas de espectroscopia no estado estacionário e resolvido no tempo. Foi possível determinar importantes parâmetros que elucidaram o potencial fotodinâmico da partícula mista ZnPC/FM com um apropriado sistema de liberação...

"Identificação e quantificação de fotossensibilizador em tecido hepático por espectroscopia de fluorescência e sua importância na terapia fotodinâmica"; "Photosensitizer identification and quantification in liver tissue by fluorescence spectroscopy and its importance on photodinamic therapy"

Vollet Filho, José Dirceu
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 26/02/2007 PT
Relevância na Pesquisa
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A Terapia Fotodinâmica (TFD) é uma técnica que provoca dano celular pela ação de um fotossensibilizador (FS), com seletividade de localização em tecido tumoral; a luz que, absorvida pelo FS, leva-o a um estado tripleto metaestável; e oxigênio molecular, o qual recebe a energia absorvida pelo FS, passando a um estado singleto de alta capacidade oxidativa. A técnica é bem sucedida no tratamento de lesões como câncer, mas enfrenta, entretanto, dificuldades para a determinação de sua dosimetria. Uma delas é a quantificação da distribuição do FS no tecido tratado. Este trabalho tem três objetivos: a obtenção de informação quantitativa por espectros de fluorescência de fluoróforos em meios turvos; a demonstração da distribuição do FS Photogem® em fígados sadios de ratos Wistar e suas implicações na dosimetria; e a melhoria de um dos modelos existentes para previsão da profundidade de necrose (Ynec), importante parâmetro no estudo da TFD. Realizaram-se os experimentos em três fases: na primeira, tentou-se reconstruir o espectro do fígado sadio a partir de uma composição de espectros isolados de fluoróforos endógenos do fígado. Na segunda, realizaram-se estudos com corantes alimentícios Coralim-Mix® nas cores azul...

Estudos fotofísicos e in vitro em modelo animal do fármaco fotossensibilizador Foscan® incorporado em nanoemulsão: avaliação como sistema de liberação em Terapia Fotodinâmica do câncer de pele; Photophysical studies and in vitro animal model of Foscan photosensitizer into nanoemulsion: evaluation as drug delivery system on Photodynamic Therapy of skin cancer

Lucas Primo, Fernando
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 25/05/2006 PT
Relevância na Pesquisa
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A Terapia Fotodinâmica (TFD) é uma modalidade terapêutica que vem atuar no tratamento de diversos tipos de câncer, com interesse crescente nas últimas décadas. Atuando de forma pouco invasiva e complementar as terapias tradicionais, a TFD consiste basicamente na administração sistêmica ou tópica de um fármaco fotossensibilizador (FS) seguido pela exposição da lesão à luz visível resultando na regressão tumoral caracterizada por processos de morte celular, sendo que, o fármaco fotossensibilizador e a radiação luminosa separadamente não induzem nenhum tipo de dano aos tecidos. A radiação monocromática utilizada na maioria dos casos é do tipo LASER sendo direcionada sobre a lesão por um conjunto de fibras ópticas. A maioria dos estudos até o presente momento sugerem um mecanismo comum de ação para a TFD. Após a excitação do fotossensibilizador para os estados excitados singlete e triplete, e por transferência de energia para o oxigênio molecular (O2) leva a morte tumoral ocasionada por espécies reativas de oxigênio definidas como EROS (1O2, O2_ ,OH, H2O2) além de outras formas radicalares (CH3, NO2, R-CO2, etc.) que atacam centros específicos dentro dos sistemas celulares, desencadeando a morte de tais tecidos por processos de necrose e/ou apoptose celular. Neste trabalho de pesquisa avaliamos a interação do fármaco fotossensibilizador Foscan® com Nanoemulsões biodegradáveis como sistemas de liberação em TFD-tópica. Na primeira etapa do trabalho foram realizados estudos físico-químicos para avaliação da estabilidade termodinâmica e determinação de alguns parâmetros morfológicos. Consecutivamente...

Caracterização físico-química e fotodinâmica de fotossensibilizadores: efeito da modificação química para aumentar a solubilidade em meio aquoso; Physical-Chemistry and photodynamic characterization of photosensitizers: effect of chemical modification to increase the solubility in aqueous medium

Gonçalves, Joyce Laura da Silva
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 29/04/2015 PT
Relevância na Pesquisa
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A hidrofobicidade e a estrutura planar do orbital π estendido de fotossensibilizadores do tipo clorina e hipericina podem favorecer a agregação destes compostos em meio aquoso. Esta agregação pode reduzir a eficiência fotodinâmica e a aplicabilidade destes compostos em diagnósticos e na Terapia fotodinâmica. Uma estratégia para minimizar esta limitação é a modificação destas moléculas pela inserção de grupos hidrofílicos. Neste trabalho foram utilizadas técnicas espectroscópicas para caracterizar as propriedades físico-químicas e fotodinâmicas de derivados de clorina (CHL), e hipericina (HY) obtidos por meio de inserções dos grupos hidrofílicos trizma e glucamina, respectivamente: Clorina-Trizma (CHL-T) e Hipericina Glucamina (HY-G). Os resultados mostraram que estas modificações estruturais aumentaram em até 20% a solubilidade destes compostos em meio aquoso. No entanto, devido à solubilidade parcial dos fotossensibilizadores na ausência de cargas elétricas foram identificados agregados do tipo H em meio ácido, neutro e na presença de íons em solução aquosa. Tais agregados foram solubilizados em meio alcalino e por microambientes micelares dos surfactantes CTAB, SDS e Tween 20. Os agregados do tipo H acarretaram ainda na redução da constante de velocidade de fotobranqueamento e da formação de oxigênio singleto dos fotossensibilizadores em meio aquoso. Contudo...

Evaluation of chitosan gel as antibiotic and photosensitizer delivery

Fontana, Carla Raquel; dos Santos Junior, David Sotero; Bosco, Joseane Maria; Spolidorio, Denise M.; Marcantonio, Rosemary Adriana Chierici
Fonte: Informa Healthcare Publicador: Informa Healthcare
Tipo: Artigo de Revista Científica Formato: 417-422
ENG
Relevância na Pesquisa
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); This work suggests the use of chitosan gel imbued with the photosensitizer Photogem and with the antibiotic Tetraclin as a possible drug delivery system. The results reveal a decrease in the photosensitizer level of toxicity. Besides, the interaction between Photogem and chitosan gel causes a red shift in the photosensitizer spectrum, increasing its absorption in the therapeutic window (600-700 nm). These characteristics indicate this compound as a promising natural polymer-based photosensitizer carrier for photodynamic therapy. In summary, our results show that pure and doped chitosan gel may have potential application for antimicrobial action, being an excellent alternative when local control of the drug administration, provided by the gel, is required.

A novel chlorin derivative of Meso-tris(pentafluorophenyl)-4-pyridylporphyrin: synthesis, photophysics and photochemical properties

Maestrin,Ana Paula J.; Ribeiro,Anderson O.; Tedesco,Antonio Cláudio; Neri,Cláudio R.; Vinhado,Fábio S.; Serra,Osvaldo A.; Martins,Patrícia R.; Iamamoto,Yassuko; Silva,Ana Margarida G.; Tomé,Augusto C.; Neves,Maria G. P. M. S.; Cavaleiro,José A. S.
Fonte: Sociedade Brasileira de Química Publicador: Sociedade Brasileira de Química
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2004 EN
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Photodynamic therapy (PDT) is based on the accumulation of a photosensitizer, such as a porphyrin or a chlorin, in a malignant tissue after its administration. Chlorins exhibit photophysical properties similar to those of the porphyrin macrocycles, but with intensified and red-shifted Q bands, making chlorin-containing systems even better candidates for PDT. In this contribution, we report the synthesis of 5,10,15-tris(pentafluorophenyl)-20-(4-pyridyl)porphyrin, (2) and its transformation to the novel chlorin derivatives 4, (5,10,20-tris(pentafluorophenyl)-15-(4-pyridyl)-tetrahydro-1H- N-methyl-pyrrolo [3,4-b]porphyrin and 5, (5,10,15-tris(pentafluorophenyl)-20-(4-pyridyl)-tetrahydro-1H- N-methyl-pyrrolo[3,4-b]porphyrin) by 1,3-dipolar cycloaddition with an azomethine ylide. The new products have been characterized by UV-Vis, ¹H NMR and FAB-MS. The photophysics, photochemical and photobleaching properties of chlorin 4 have been evaluated. Its quantum yield of photobleaching (phiPb, mol Einstein-1) was 0.047±0.014. In order to demonstrate the production of ¹O2 when 4 is used as a photosensitizer, uric acid tests have been carried out. The results indicate that chlorin 4 can be considered a promising photosensitizer in PDT.

Photosensitizer binding to lipid bilayers as a precondition for the photoinactivation of membrane channels.

Rokitskaya, T I; Block, M; Antonenko, Y N; Kotova, E A; Pohl, P
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/2000 EN
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The photodynamic activity of sulfonated aluminum phthalocyanines (AlPcS(n), 1

Minimally-invasive debulking of ovarian cancer in the rat pelvis by means of photodynamic therapy using the pegylated photosensitizer PEG-m-THPC

Hornung, R; Fehr, M K; Monti-Frayne, J; Tromberg, B J; Berns, M W; Tadir, Y
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em /10/1999 EN
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Interstitial photodynamic therapy (PDT) using the pegylated photosensitizer PEG-m-THPC was evaluated as a minimally-invasive procedure to selectively debulk unrespectable pelvic ovarian cancer (NuTu-19) in immunocompetent rats. To assess tumour selectivity, PEG-m-THPC at dosages of 0.3, 3.0 and 30 mg kg−1 body weight was administered intravenously to 30 rats 4 weeks following tumour induction. Eight days later laser light at 652 nm and optical doses ranging from 100 to 900 J cm−1 diffuser-length was delivered by an interstitial cylindrical diffusing fibre inserted blindly into the pelvis. Three days following light application, the volume of necrosis was measured and the damage to pelvic organs was assessed histologically on cross sections. For analysis of survival, 20 tumour-bearing rats received PDT using drug doses of 3 or 9 mg kg−1 body weight and an optical dose of 900 J cm−1 diffuser-length, whereas ten untreated tumour-bearing rats served as controls. The histological assessment of PDT induced necrosis showed a non-linear dose–response for both the photosensitizer dose and the optical dose. The lowest drug dose activated with the highest optical dose did not induce more necrosis than seen in tumour-bearing control animals. The same optical dose induced necrosis of 17 mm in diameter using 30 mg kg−1 and 11 mm using 3 mg kg−1 photosensitizer. The optical threshold for induction of significant necrosis was between 100 and 300 J cm−1 diffuser-length for 30 mg kg−1 and between 300 and 500 J cm−1 for 3 mg kg−1 PEG-m-THPC. Significant damage to normal pelvic organs was only seen if 30 mg kg−1 photosensitizer was activated with optical doses of 700 J cm−1 or more. In the survival study...

Intratumor Administration of the Photosensitizer Pc 4 Affords Photodynamic Therapy Efficacy and Selectivity at Short Drug-Light Intervals1

Foster, Thomas H; Giesselman, Benjamin R; Hu, Rui; Kenney, Malcolm E; Mitra, Soumya
Fonte: Neoplasia Press Inc. Publicador: Neoplasia Press Inc.
Tipo: Artigo de Revista Científica
Publicado em /04/2010 EN
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We evaluated intratumor (IT) versus intravenous (IV) administration of the photosensitizer Pc 4 with respect to tumor photosensitizer concentration, specificity, and responses to irradiation. BALB/c mice bearing intradermal EMT6 tumors were given 0.3 mg/kg Pc 4 injected IT or IV through the tail vein. Photosensitizer concentration was evaluated by chloroform extraction and localization assessed by fluorescence imaging and spectroscopy in vivo. Tumors were irradiated at 667 nm, 50 mW/cm2, and 100 J/cm2. Cures were defined as no palpable tumor 90 days after irradiation. Tumor Pc 4 concentrations 1 hour after IT administration were 35,000-fold higher than measured 24 hours after IV administration (0.112 vs 0.317 x 10-5 µg Pc 4/mg tumor). Exquisite tumor selectivity was observed 1 hour after IT injection. Fluorescence imaging of freshly sectioned tumors revealed no regions devoid of sensitizer at this time point, with pixel intensities in a midline section within a factor of 3 of the peak intensity. For identical photosensitizer doses, IT administration significantly improved tumor responses to irradiation, with more than 70% of tumors cured with IT-Pc 4-PDT. In this model, IT-Pc 4 administration provides improved tumor control, greater selectivity...

Targeted Delivery of a Photosensitizer to Aggregatibacter actinomycetemcomitans Biofilm▿ †

Suci, Peter; Kang, Sebyung; Gmür, Rudolf; Douglas, Trevor; Young, Mark
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
EN
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The ability to selectively target specific biofilm species with antimicrobials would enable control over biofilm consortium composition, with medical applications in treatment of infections on mucosal surfaces that are colonized by a mixture of beneficial and pathogenic microorganisms. We functionalized a genetically engineered multimeric protein with both a targeting moiety (biotin) and either a fluorophore or a photosensitizer (SnCe6). Biofilm microcolonies of Aggregatibacter actinomycetemcomitans, a periodontal pathogen, were targeted with the multifunctional dodecamer. Streptavidin was used to couple biotinylated dodecamer to a biotinylated anti-A. actinomycetemcomitans antibody. This modular targeting approach enabled us to increase the loading of photosensitizer onto the cells by a cycle of amplification. Scanning laser confocal microscopy was used to characterize transport of fluorescently tagged dodecamer into the microcolonies and targeting of the cells with biotin-labeled, fluorescently tagged dodecamer. Light-induced activity of the targeted photosensitizer reduced the viability of A. actinomycetemcomitans biofilm, as indicated by membrane permeability to propidium iodide. The functionalized multimeric protein promises to be a useful tool for controlling periodontal biofilm consortia and offers a modular design whereby moieties that target different species can be readily combined with the functionalized protein construct.

Cell specific aptamer-photosensitizer conjugates as a molecular tool in photodynamic therapy

Mallikaratchy, Prabodhika; Tang, Zhiwen; Tan, Weihong
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/2008 EN
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This paper describes the application of a molecular construct of a photosensitizer and an aptamer for photo-therapeutically targeting tumor cells. The key step in increasing selectivity in chemotherapeutic drugs is to create effective molecular platforms that could target cancer cells but not normal cells. Recently, we have developed a strategy via cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) to obtain cell specific aptamers using intact viable cells as targets to select aptamers that can recognize cell membrane proteins with high selectivity and excellent affinity. We have identified an aptamer TD05 that only recognizes Ramos cells, a Burkitt’s lymphoma cell line. Here, the high specificity of aptamers in target cell binding and an efficient phototherapy reagent, Ce6, are molecularly engineered to construct a highly selective Aptamer-photosensitizer conjugates (APS) to effectively destroy target cancer cells. Introduction of the APS conjugates followed by irradiation of light selectively destroyed target Ramos cells but not acute lymphoblastic leukemia and myeloid leukemia cell lines. This study demonstrates that the use of cancer specific aptamers conjugated to a photosensitizer will enhance the selectivity of photodynamic therapy. Coupled with the advantages of the cell-SELEX in generating multiple effective aptamers for diseased cell recognition...

Photosensitizer delivery to vulnerable atherosclerotic plaque: comparison of macrophage-targeted conjugate versus free chlorine(e6)

Tawakol, Ahmed; Castano, Ana P.; Anatelli, Florencia; Bashian, Gregory; Stern, Jeremy; Zahra, Touqir; Gad, Faten; Chirico, Stephanie; Ahmadi, Atosa; Fischman, Alan J.; Muller, James E.; Hamblin, Michael R.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em //2006 EN
Relevância na Pesquisa
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We have previously shown that a conjugate (MA-ce6) between maleylated serum albumin and the photosensitizer chlorin(e6) (ce6) is targeted in vitro to macrophages via class A scavenger receptors. We now report on the ability of this conjugate to localize in macrophage-rich atherosclerotic plaques in vivo. Both the conjugate and the free photosensitizer ce6 are studied after injection into New Zealand White rabbits that are rendered atherosclerotic by a combination of aortic endothelial injury and cholesterol feeding into normal rabbits. Rabbits are sacrificed at 6 and 24 h after injection and intravascular fluorescence spectroscopy is carried out by fiber-based fluorimetry in intact blood-filled arteries. Surface spectrofluorimetry of numbered excised aortic segments together with injured and normal iliac arteries is carried out, and quantified ce6 content by subsequent extraction and quantitative fluorescence determination of the arterial segments and also of nontarget organs. There is good agreement between the various techniques for quantifying ce6 localization, and high contrast between arteries from atherosclerotic and normal rabbits is obtained. Fluorescence correlates with the highest burden of plaque in the aorta and the injured iliac artery. The highest accumulation in plaques is obtained using MA-ce6 at 24 h. Free ce6 gives better accumulation at 6 h compared to 24 h. The liver...

Receptor-Targeting Phthalocyanine Photosensitizer for Improving Antitumor Photocytotoxicity

Xu, Peng; Chen, Jincan; Chen, Zhuo; Zhou, Shanyong; Hu, Ping; Chen, Xueyuan; Huang, Mingdong
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 31/05/2012 EN
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Photodynamic therapy (PDT) is a promising therapeutic modality which uses a photosensitizer to capture visible light resulting in phototoxicity in the irradiated region. PDT has been used in a number of pathological indications, including tumor. A key desirable feature of the photosensitizer is the high phototoxicity on tumor cells but not on normal cells. In this study, we conjugate a gonadotropin-releasing hormone (GnRH) to a photosensitizer, Zinc phthalocyanine (ZnPc), in order to enhance its specificity to breast cancer, which over-expresses GnRH receptor. ZnPc has unique advantages over other photosensitizers, but is difficult to derivatize and purify as a single isomer. We previously developed a straight-forward way to synthesize mono-substituted β-carboxy-phthalocyanine zinc (ZnPc-COOH). Photophysical and photochemical parameters of this ZnPc-GnRH conjugate including fluorescence quantum yield (Фf), fluorescence decay time (τs) and singlet oxygen quantum yield (ФΔ) were evaluated and found comparable with that of ZnPc, indicating that addition of a GnRH peptide does not significantly alter the generation of singlet oxygen from ZnPc. Cellular uptakes and phototoxicities of this conjugate were tested and found significantly enhanced on human breast cancer cell lines overexpressing GnRH receptors (MDA-MB-231 and MCF-7 cells) compared to cells with low levels of GnRH receptors...

Photochemical model of Photodynamic Therapy applied to skin diseases by a topical photosensitizer

Fanjul Vélez, Félix; Salas García, Irene; Fernández Fernández, Luis Alberto; López-Escobar García-Prendes, María; Buelta Carrillo, Luis; Ortega Quijano, Noé; Arce Diego, José Luis
Fonte: The Optical Society (OSA)-; SPIE Society of Photo-Optical Instrumentation Engineers Publicador: The Optical Society (OSA)-; SPIE Society of Photo-Optical Instrumentation Engineers
Tipo: info:eu-repo/semantics/conferenceObject; publishedVersion
ENG
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Photodynamic Therapy (PDT) provides a non-invasive, efficient and safe treatment for skin diseases with good cosmetic results. These characteristics make this technique more advantageous than radiotherapy or chemotherapy, which present limitations in a big number of lesions, are painful in many cases and produce non-satisfactory cosmetic results. We present the clinical results obtained at present by this optical technique and a photochemical model of the PDT process applied to the skin by means of a topical photosensitizer, in order to find the optimal PDT parameters. Optical propagation inside the tissue is calculated by means of the three dimensional Beer-Lambert law, due to its facility to be integrated in the differential equations system used to model the photochemical processes involved. With this information it is possible to obtain an initial estimation about the optimal drug dose and the optical power required.

Predictive model for Photodynamic Therapy with gold nanoparticles as vehicle for the photosensitizer delivery

Salas García, Irene; Fanjul Vélez, Félix; Ortega Quijano, Noé; Arce Diego, José Luis
Fonte: The Optical Society (OSA)-; SPIE Society of Photo-Optical Instrumentation Engineers Publicador: The Optical Society (OSA)-; SPIE Society of Photo-Optical Instrumentation Engineers
Tipo: info:eu-repo/semantics/conferenceObject; publishedVersion
ENG
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Photodynamic Therapy offers multiple advantages to treat nonmelanoma skin cancer compared to conventional treatment techniques such as surgery, radiotherapy or chemotherapy. Among these advantages are particularly relevant its noninvasive nature, the use of non ionizing radiation and its high selectivity. However the therapeutic efficiency of the current clinical protocol is not complete in all the patients and depends on the type of pathology. Emerging strategies to overcome its current shortcomings include the use of nanostructures that can act as carriers for conventional photosensitizers and improve the treatment selectivity and provide a controlled release of the photoactive agent. In this work, a model for photodynamic therapy combined with gold nanocarriers for a photosensitizer commonly used in dermatology is presented and applied to a basal cell carcinoma in order to predict the cytotoxic agent spatial and temporal evolution.

Insights into Photodynamic Therapy Dosimetry: Simultaneous Singlet Oxygen Luminescence and Photosensitizer Photobleaching Measurements

Jarvi, Mark T.; Patterson, Michael S.; Wilson, Brian C.
Fonte: The Biophysical Society Publicador: The Biophysical Society
Tipo: Artigo de Revista Científica
Publicado em 08/02/2012 EN
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Photodynamic therapy (PDT) is generally based on the generation of highly reactive singlet oxygen (1O2) through interactions of photosensitizer, light, and oxygen (3O2). These three components are highly interdependent and dynamic, resulting in variable temporal and spatial 1O2 dose deposition. Robust dosimetry that accounts for this complexity could improve treatment outcomes. Although the 1270 nm luminescence emission from 1O2 provides a direct and predictive PDT dose metric, it may not be clinically practical. We used 1O2 luminescence (or singlet oxygen luminescence (SOL)) as a gold-standard metric to evaluate potentially more clinically feasible dosimetry based on photosensitizer bleaching. We performed in vitro dose-response studies with simultaneous SOL and photosensitizer fluorescence measurements under various conditions, including variable 3O2, using the photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC). The results show that SOL was always predictive of cytotoxicity and immune to PDT's complex dynamics, whereas photobleaching-based dosimetry failed under hypoxic conditions. However, we identified a previously unreported 613 nm emission from mTHPC that indicates critically low 3O2 levels and can be used to salvage photobleaching-based dosimetry. These studies improve our understanding of PDT processes...