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The role of strong hypoxia in tumors after treatment in the outcome of bacteriochlorin-based photodynamic therapy

Krzykawska-Serda, Martyna; Dąbrowski, Janusz M.; Arnaut, Luis G.; Szczygieł, Małgorzata; Urbańska, Krystyna; Stochel, Grażyna; Elas, Martyna
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
27.42%
Blood flow and pO2 changes after vascular-targeted photodynamic therapy (V-PDT) or cellular-targeted PDT (C-PDT) using 5,10,15,20-tetrakis(2,6-difluoro-3-N-methylsulfamoylphenyl) bacteriochlorin (F2BMet) as photosensitizer were investigated in DBA/2 mice with S91 Cloudman mouse melanoma, and correlated with long-term tumor responses. F2BMet generates both singlet oxygen and hydroxyl radicals under near-infrared radiation, which consume oxygen. Partial oxygen pressure was lowered in PDT-treated tumors and this was ascribed both to oxygen consumption during PDT and to fluctuations in oxygen transport after PDT. Similarly, microcirculatory blood flow changed as a result of the disruption of blood vessels by the treatment. A novel noninvasive approach combining electron paramagnetic resonance oximetry and laser Doppler blood perfusion measurements allowed longitudinal monitoring of hypoxia and vascular function changes in the same animals, after PDT. C-PDT induced parallel changes in tumor pO2 and blood flow, i.e., an initial decrease immediately after treatment, followed by a slow increase. In contrast, V-PDT led to a strong and persistent depletion of pO2, although the microcirculatory blood flow increased. Strong hypoxia after V-PDT led to a slight increase in VEGF level 24 h after treatment. C-PDT caused a ca. 5-day delay in tumor growth...

Mitochondria, endoplasmic reticulum and actin filament behavior after PDT with chloroaluminum phthalocyanine liposomal in HeLa cells

MAFTOUM-COSTA, Maira; NAVES, Karina Teixeira; OLIVEIRA, Alexandre Lima; TEDESCO, Antonio Claudio; SILVA, Newton Soares da; PACHECO-SOARES, Cristina
Fonte: ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD Publicador: ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
37.1%
Photodynamic therapy (PDT) for cancer is a therapeutic modality in the treatment of tumors in which visible light is used to activate a photosensitizer. Cell membranes have been identified as an important intracellular target for singlet oxygen produced during the photochemical pathway. This study analyzed the cytotoxicity in specific cellular targets of a photosensitizer used in PDT in vitro. The photosensitizing effects of chloroaluminum phthalocyanine liposomal were studied on the mitochondria, cytoskeleton and endoplasmic reticulum of HeLa cells. Cells were irradiated with a diode laser working at 670 nm, energy density of 4.5 J/cm(2) and power density of 45 mW/cm(2). Fluorescence microscopic analysis of the mitochondria showed changes in membrane potential. After PDT treatment, the cytoskeleton and endoplasmic reticulum presented basic alterations in distribution. The combined effect of AlPHCl liposomal and red light in the HeLa cell line induced photodamage to the mitochondria, endoplasmic reticulum and actin filaments in the cytoskeleton. (c) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.; FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo; CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)

Biocompatible Magnetic Microspheres for Use in PDT and Hyperthermia

Vaccari, C. B.; Cerize, N. N. P.; Morais, P. C.; Re, M. I.; Tedesco, Antonio Claudio
Fonte: AMER SCIENTIFIC PUBLISHERS; VALENCIA Publicador: AMER SCIENTIFIC PUBLISHERS; VALENCIA
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
36.86%
Loaded microspheres with a silicon (IV) phthalocyanine derivative (NzPC) acting as a photosensitizer were prepared from polyhydroxybutyrate-co-valerate (PHBHV) and poly(ecaprolactone) (PCL) polymers using the emulsification solvent evaporation method (EE). The aim of our study was to prepare two systems of these biodegradable PHBHV/PCL microspheres. The first one containing only photosensitizer previously incorporated in the PHBHV and poly(ecaprolactone) (PCL) microspheres and the second one with the post magnetization of the DDS with magnetic nanoparticles. Magnetic fluid is successfully used for controlled incorporation of nanosized magnetic particles within the micron-sized template. This is the first time that we could get a successful pos incorporation of nanosized magnetic particles in a previously-prepared polymeric template. This procedure opens a great number of possibilities of post-functionalization of polymeric micro or nanoparticles with different bioactive materials. The NzPC release profile of the systems is ideal for PDT, the zeta potential and the size particle are stable upon aging in time. In vitro studies were evaluated using gingival fibroblastic cell line. The dark citotoxicity, the phototoxicity and the AC magnetic field assays of the as-prepared nanomagnetic composite were evaluated and the cellular viability analyzed by the classical test of MU.; Brazilian agency FAPESP; Brazilian agency FAPESP [06/57129-1...

Photodynamic therapy induced vascular damage: an overview of experimental PDT

Wang, W.; Moriyama, Lilian Tan; Bagnato, Vanderlei Salvador
Fonte: Institute of Physics - IOP; Bristol Publicador: Institute of Physics - IOP; Bristol
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
27.29%
Photodynamic therapy (PDT) has been developed as one of the most important therapeutic options in the treatment of cancer and other diseases. By resorting to the photosensitizer and light, which convert oxygen into cytotoxic reactive oxygen species (ROS), PDT will induce vascular damage and direct tumor cell killing. Another consequence of PDT is the microvascular stasis, which results in hypoxia and further produces tumor regression. To improve the treatment with PDT, three promising strategies are currently attracting much interest: (1) the combination of PDT and anti-angiogenesis agents, which more effectively prevent the proliferation of endothelial cells and the formation of new blood vessels; (2) the nanoparticle-assisted delivery of photosensitizer, which makes the photosensitizer more localized in tumor sites and thus renders minimal damage to the normal tissues; (3) the application of intravascular PDT, which can avoid the loss of energy during the transmission and expose the target area directly. Here we aim to review the important findings on vascular damage by PDT on mice. The combination of PDT with other approaches as well as its effect on cancer photomedicine are also reviewed.; CNPq

Comparação da eficácia do ácido 5-aminolevulínico com a de seu metil éster utilizando-se a terapia fotodinâmica no tratamento de carcinoma espinocelular felino; COMPARISON OF EFFICACIES OF ALA-PDT AND METHYL AMINOLEVULINATE-PDT IN THE TREATMENT OF FELINE SQUAMOUS CELL CARCINOMA

Emilio, Claudia Rodrigues
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 12/09/2008 PT
Relevância na Pesquisa
27.32%
A comparação dos resultados obtidos utilizando-se uma única sessão de terapia fotodinâmica (PDT) com diodos emissores de luz (LEDs) de 630 nm no tratamento de carcinoma espinocelular (CEC) de gatos foi o objetivo principal do presente estudo, onde duas diferentes composições de precursores da protoporfirina IX (PPIX), o metil aminolevulinato (MEALA) e o ácido aminolevulínico (ALA) foram testados. Dezenove animais com um total de 24 lesões de CEC cutâneo confirmadas pelo estudo histopatológico foram distribuídos em dois grupos; o primeiro foi tratado com MEALA e o segundo com ALA. Pelos resultados negativos em testes sorológicos para detecção dos vírus da imunodeficiência felina (FIV) e vírus da leucemia felina (FeLV), não foi possível correlacionar a ocorrência dessas doenças virais com a incidência de CEC cutâneo nos gatos estudados. A temperatura da superfície cutânea, monitorada durante a PDT não apresentou aumento significativo (t < 3oC) nos dois grupos. Todos os animais foram submetidos a exame clínico e sanguíneo (hemograma e função hepato-renal) antes e após o tratamento, não havendo nenhuma alteração que inviabilizasse a inclusão dos mesmos no protocolo experimental e nem alterações atribuídas ao tratamento. A quantificação imunoistoquímica para o antígeno nuclear de proliferação celular (PCNA) foi realizada como um fator prognóstico do tratamento...

Desenvolvimento de biofilme formado por Candida albicans in vitro para estudo do efeito fotodinâmico; Candida albicans BIOFILM DEVELOPMENT IN VITRO FOR PHOTODYNAMIC THERAPY STUDY

Suzuki, Luis Claudio
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 25/09/2009 PT
Relevância na Pesquisa
27.41%
A terapia fotodinâmica, do inglês photodynamic therapy (PDT) é uma fototerapia baseada na utilização de um fotossensibilizador (FS) na presença da luz em baixa intensidade em comprimento de onda ressonante à absorção do FS e que podem sensibilizar sistemas biológicos, gerando espécies reativas de oxigênio. Estudos mostram que a PDT apresenta um efeito letal em Candida albicans. O biofilme formado por C. albicans é a causa mais freqüente de infecções associadas a cateteres, possuindo uma comprovada resistência a antifúngicos, sendo que a remoção do cateter colonizado é quase sempre necessária. No entanto, poucos trabalhos na literatura relatam o comportamento e a resposta de C. albicans organizado em biofilme frente à PDT. Os objetivos deste trabalho foram desenvolver uma metodologia para formação in vitro de biofilme de C. albicans, verificar a sensibilidade do biofilme de C. albicans frente à terapia fotodinâmica antimicrobiana utilizando como FS o azul de metileno (AM) e a hipocrelina B:La+3 e analisar o biofilme através da Tomografia de Coerência Óptica (OCT) antes e depois da PDT. Para a formação do biofilme, foram confeccionados discos de silicone elastomérico oriundos de cateteres. Os fotossensibilizadores foram diluídos em solução de PBS...

Avaliação do efeito vascular da terapia fotodinâmica empregando derivados de porfirina e clorina na membrana corioalantóica; Evaluation of vascular effect of photodynamic therapy using porphiryn and chlorin derivates in the chorioallantoic membrane

Buzzá, Hilde Harb
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 10/02/2012 PT
Relevância na Pesquisa
27.29%
A Terapia Fotodinâmica (do inglês, Photodynamic Therapy - PDT) é uma técnica indicada para o tratamento local de câncer que vem tendo grandes avanços ao longo dos anos. A PDT consiste na interação entre luz e uma substância fotossensibilizadora, resultando na transformação do oxigênio molecular em oxigênio singleto, altamente reativo e tóxico para a célula, levando à destruição do tecido. Nesse contexto, o uso do modelo de Membrana Corioalantóica (CAM) é uma opção para o estudo dos efeitos vasculares envolvidos nessa terapia, além de permitir o estudo na variação de diversos parâmetros associados com a PDT e seus efeitos. Nesse estudo foram investigados um composto derivado de porfirina e um derivado de clorina. Esses fotossensibilizadores foram administrados topicamente e por via intravenosa, sendo variados diversos parâmetros. No primeiro caso, o tempo de incubação foi variado entre 20 e 80 minutos e a concentração de área da droga foi variada entre 0,1 e 100 g/cm2. Quanto à dose de luz, o intervalo foi entre 4,8 e 60 J/cm2, empregando lasers de diodo em 635 nm para Photogem® e 660 nm para Photodithazine®. Depois de estabelecido 30 J/cm² para a aplicação tópica, foi usada a aplicação intravenosa com essa dose...

Espectroscopia de fluorescência na otimização da terapia fotodinâmica em carcinoma espinocelular de pele e sua avaliação utilizando tomografia por coerência óptica; Fluorescence spectroscopy in the optimization of photodynamic therapy of skin squamous cell carcinoma and its evaluation by optical coherence tomography

Goulart, Viviane Pereira
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 07/12/2012 PT
Relevância na Pesquisa
27.32%
A terapia fotodinâmica (PDT) é uma alternativa promissora de tratamento para lesões pré-cancerosas e para câncer de pele não-melanoma, como o carcinoma espinocelular, agressivo e potencialmente metastático. Visando melhorar a eficiência da terapia fotodinâmica de carcinoma espinocelular de pele, este estudo otimizou o tempo para início da terapia, avaliou a eficácia dos fotossensibilizadores ácido aminolevulínico (ALA- 20%) e o metil-ester aminolevulínico (MEALA-10%) e verificou o coeficiente de atenuação relativo à pele normal dos grupos experimentais, por meio de Tomografia por Coerência Óptica. Para a indução do tumor foi realizada a carcinogênese química (DMBA/TPA) por um período de 28 semanas. A espectroscopia de fluorescência foi utilizada para monitoração da emissão da molécula de protoporfirina IX, induzida pelo ALA e MEALA. A aquisição de dados a cada 30 minutos totalizando um período de 360 minutos, permitiu verificar a máxima incorporação de ALA e MEALA em 300 e 330 minutos após a aplicação, respectivamente. Após a otimização foi realizada a PDT, avaliação clínica, histopatológica e análise por OCT dos grupos experimentais, por meio das quais verificou-se maior eficiência do grupo tratado com MEALA. No período de 20 dias...

Desenvolvimento dos conceitos básicos para dosimetria e aplicação em terapia fotodinâmica; Development of basic concepts for PDT dosimetry and application

Melo, Claudia Adriana de Sousa
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 18/07/2003 PT
Relevância na Pesquisa
27.29%
A Terapia Fotodinâmica (PDT) é a uma modalidade terapêutica promissora para o tratamento do câncer e outras doenças, que visa a destruição do tecido alterado. A PDT se caracteriza por um conjunto de processos físicos, químicos e biológicos que ocorrem após a administração de uma droga, retida preferencialmente nos tecidos tumorais, seguida pela irradiação com luz visível. Quando as células tumorais tratadas são irradiadas, o fotossensibilizador absorve luz e inicia uma reação em cadeia produzindo espécies reativas de oxigênio que destroem as células tumorais. Neste trabalho procuramos avaliar os principais aspectos da PDT para o desenvolvimento de uma dosimetria baseada em conceitos fundamentais tais como: a estabilidade do Photogem ®, a farmacocinética, a penetração da luz no tecido e os mecanismos de morte celular. Com esse propósito realizamos quatro experimentos distintos nos quais esses aspectos foram investigados. Realizamos experimentos in vitro para averiguar a estabilidade do Photogem ®. As soluções foram submetidas a condições extremas de irradiação, onde variamos comprimentos de onda e potência de irradiação. Analisamos também a variação de pH, concentração e solvente. A farmacocinética...

Terapia fotodinâmica no tratamento do tumor de Ehrlich inoculado em camundongos: avaliação da eficácia e da resposta imunológica sistêmica; Photodynamic Therapy in the treatment of Ehrlich solid tumor in mice: efficacy evaluation and the systemic immune response

Grande, Murilo Penteado Del
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 13/05/2013 PT
Relevância na Pesquisa
27.32%
A terapia fotodinâmica (Photodynamic Therapy - PDT) é um método de tratar neoplasias baseado na interação entre luz, oxigênio molecular e um agente fotossensibilizador. Após a administração do agente, o tumor é iluminado com luz visível, ativando-o e produzindo espécies reativas de oxigênio, altamente citotóxicas, que provocam morte celular e destruição tecidual. Com a destruição do tumor há ativação do sistema imune inato e o subsequente processo inflamatório determina a apresentação de antígenos tumorais aos linfócitos, promovendo uma resposta imunológica adaptativa contra o tecido tumoral. O presente trabalho visou estudar a PDT associando um laser de diodo como fonte de luz e o fotossensibilizante Azul de Metileno (AM) a 1%, avaliando a sua efetividade no tratamento do Tumor de Ehrlich (TE) em sua forma sólida e a resposta imunológica nos animais tratados. Em um primeiro estudo, avaliou-se macro e microscopicamente tumores tratados, determinando a capacidade do protocolo em induzir inflamação e destruição do tecido tumoral. No segundo estudo, a resposta imune foi estudada em camundongos desafiados com um segundo implante de células do tumor de Ehrlich. O primeiro implante tumoral foi tratado com a PDT ou a excisão cirúrgica...

Increased tumour dihydroceramide production after Photofrin-PDT alone and improved tumour response after the combination with the ceramide analogue LCL29. Evidence from mouse squamous cell carcinomas

Separovic, D; Bielawski, J; Pierce, J S; Merchant, S; Tarca, A L; Ogretmen, B; Korbelik, M
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.34%
Photodynamic therapy (PDT) has been proven effective for treatment of several types of cancer. Photodynamic therapy alone, however, attains limited cures with some tumours and there is need for its improved efficacy in such cases. Sphingolipid (SL) analogues can promote tumour response in combination with anticancer drugs. In this study, we used mouse SCCVII squamous cell carcinoma tumours to determine the impact of Photofrin-PDT on the in vivo SL profile and the effect of LCL29, a C6-pyridinium ceramide, on PDT tumour response. Following PDT, the levels of dihydroceramides (DHceramides), in particular C20-DHceramide, were elevated in tumours. Similarly, increases in DHceramides, in addition to C20:1-ceramide, were found in PDT-treated SCCVII cells. These findings indicate the importance of the de novo ceramide pathway in Photofrin-PDT response not only in cells but also in vivo. Notably, co-exposure of SCCVII tumours to Photofrin-PDT and LCL29 led to enhanced tumour response compared with PDT alone. Thus, we show for the first time that Photofrin-PDT has a distinct signature effect on the SL profile in vitro and in vivo, and that the combined treatment advances PDT therapeutic gain, implying translational significance of the combination.

Increasing Damage to Tumor Blood Vessels during Motexafin Lutetium-PDT through Use of Low Fluence Rate

Busch, Theresa M.; Wang, Hsing-Wen; Wileyto, E. Paul; Yu, Guoqiang; Bunte, Ralph M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/2010 EN
Relevância na Pesquisa
27.32%
Photodynamic therapy (PDT) with low light fluence rate has rarely been studied in protocols that use short drug–light intervals and thus deliver illumination while plasma concentrations of photosensitizer are high, creating a prominent vascular response. In this study, the effects of light fluence rate on PDT response were investigated using motexafin lutetium (10 mg/kg) in combination with 730 nm light and a 180-min drug–light interval. At 180 min, the plasma level of photosensitizer was 5.7 ng/μl compared to 3.1 ng/mg in RIF tumor, and PDT-mediated vascular effects were confirmed by a spasmodic decrease in blood flow during illumination. Light delivery at 25 mW/cm2 significantly improved long-term tumor responses over that at 75 mW/cm2. This effect could not be attributed to oxygen conservation at low fluence rate, because 25 mW/cm2 PDT provided little benefit to tumor hemoglobin oxygen saturation. However, 25 mW/cm2 PDT did prolong the duration of ischemic insult during illumination and was correspondingly associated with greater decreases in perfusion immediately after PDT, followed by smaller increases in total hemoglobin concentration in the hours after PDT. Increases in blood volume suggest blood pooling from suboptimal vascular damage; thus the smaller increases after 25 mW/cm2 PDT provide evidence of more widespread vascular damage...

Structures of Open (R) and Close (T) States of Prephenate Dehydratase (PDT) - Implication of Allosteric Regulation by L-Phenylalanine

Tan, Kemin; Li, Hui; Zhang, Rongguang; Gu, Minyi; Clancy, Shonda T.; Joachimiak, Andrzej
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.29%
The enzyme prephenate dehydratase (PDT) converts prephenate to phenylpyruvate in L-phenylalanine biosynthesis. PDT is allosterically regulated by L-Phe and other amino acids. We report the first crystal structures of PDT from Staphylococcus aureus in a relaxed (R) state and PDT from Chlorobium tepidum in a tense (T) state. The two enzymes show low sequence identity (27.3%) but the same prototypic architecture and domain organization. Both enzymes are tetramers (dimer of dimers) in crystal and solution while a PDT dimer can be regarded as a basic catalytic unit. The N-terminal PDT domain consists of two similar subdomains with a cleft in between, which hosts the highly conserved active site. In one PDT dimer two clefts are aligned to form an extended active site across the dimer interface. Similarly at the interface two ACT regulatory domains create two highly conserved pockets. Upon binding of the L-Phe inside the pockets, PDT transits from an open to a closed conformation.

Photodynamic therapy activated signaling from epidermal growth factor receptor and STAT3: Targeting survival pathways to increase PDT efficacy in ovarian and lung cancer

Edmonds, Christine; Hagan, Sarah; Gallagher-Colombo, Shannon M.; Busch, Theresa M.; Cengel, Keith A.
Fonte: Landes Bioscience Publicador: Landes Bioscience
Tipo: Artigo de Revista Científica
Publicado em 01/12/2012 EN
Relevância na Pesquisa
27.42%
Patients with serosal (pleural or peritoneal) spread of malignancy have few definitive treatment options and consequently have a very poor prognosis. We have previously shown that photodynamic therapy (PDT) can be an effective treatment for these patients, but that the therapeutic index is relatively narrow. Here, we test the hypothesis that EGFR and STAT3 activation increase survival following PDT, and that inhibiting these pathways leads to increased PDT-mediated direct cellular cytotoxicity by examining BPD-PDT in OvCa and NSCLC cells. We found that BPD-mediated PDT stimulated EGFR tyrosine phosphorylation and nuclear translocation, and that EGFR inhibition by erlotinib resulted in reduction of PDT-mediated EGFR activation and nuclear translocation. Nuclear translocation and PDT-mediated activation of EGFR were also observed in response to BPD-mediated PDT in multiple cell lines, including OvCa, NSCLC and head and neck cancer cells, and was observed to occur in response to porfimer sodium-mediated PDT. In addition, we found that PDT stimulates nuclear translocation of STAT3 and STAT3/EGFR association and that inhibiting STAT3 signaling prior to PDT leads to increased PDT cytotoxicity. Finally, we found that inhibition of EGFR signaling leads to increased PDT cytotoxicity through a mechanism that involves increased apoptotic cell death. Taken together...

PDT Dose Parameters Impact Tumoricidal Durability and Cell Death Pathways in a 3D Ovarian Cancer Model

Rizvi, Imran; Anbil, Sriram; Alagic, Nermina; Celli, Jonathan P.; Zheng, Lei Zak; Palanisami, Akilan; Glidden, Michael D.; Pogue, Brian W.; Hasan, Tayyaba
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.32%
The successful implementation of photodynamic therapy (PDT)-based regimens depends on an improved understanding of the dosimetric and biological factors that govern therapeutic variability. Here, the kinetics of tumor destruction and regrowth are characterized by systematically varying benzoporphyrin derivative (BPD)-light combinations to achieve fixed PDT doses (M × J/cm2). Three endpoints were used to evaluate treatment response: 1.) Viability evaluated every 24 hours for 5 days post-PDT; 2.) Photobleaching assessed immediately post-PDT; and 3.) Caspase-3 activation determined 24-hours post-PDT. The specific BPD-light parameters used to construct a given PDT dose significantly impact not only acute cytotoxic efficacy, but also treatment durability. For each dose, PDT with 0.25 μM BPD produces the most significant and sustained reduction in normalized viability compared to 1 μM and 10 μM BPD. Percent photobleaching correlates with normalized viability for a range of PDT doses achieved within BPD concentrations. To produce a cytotoxic response with 10 μM BPD that is comparable to 0.25 μM and 1 μM BPD a reduction in irradiance from 150 mW/cm2 to 0.5 mW/cm2 is required. Activated caspase-3 does not correlate with normalized viability. The parameter-dependent durability of outcomes within fixed PDT doses provides opportunities for treatment customization and improved therapeutic planning.

Comparative Tumor Imaging and PDT Efficacy of HPPH Conjugated in the Mono- and Di-Forms to Various Polymethine Cyanine Dyes: Part - 2

James, Nadine S.; Ohulchanskyy, Tymish Y.; Chen, Yihui; Joshi, Penny; Zheng, Xiang; Goswami, Lalit N.; Pandey, Ravindra K.
Fonte: Ivyspring International Publisher Publicador: Ivyspring International Publisher
Tipo: Artigo de Revista Científica
Publicado em 21/08/2013 EN
Relevância na Pesquisa
27.29%
Previous reports from our laboratory have shown that a bifunctional agent obtained by conjugating a photosensitizer (HPPH) to a cyanine dye (CD) can be used for fluorescence image-guided treatment of tumor by photodynamic therapy (PDT). However, the resulting HPPH-CD conjugate showed a significant difference between the tumor-imaging and therapeutic doses. It was demonstrated that the singlet oxygen (1O2*, a key cytotoxic agent in PDT) produced by the conjugate upon excitation of the HPPH moiety was partially quenched by the CD-moiety; this resulted in a reduced PDT response when compared to HPPH-PDT under similar treatment parameters. To improve the therapeutic potential of the conjugate, we synthesized a series of dual functional agents in which one or two HPPH moieties were separately conjugated to three different dyes (Cypate, modified IR820 or modified IR783). The newly synthesized conjugates were compared with our lead compound HPPH-CD in terms of photophysical properties, in vitro and in vivo PDT efficacy, tumor uptake and imaging potential. Among the analogs investigated, the conjugate, in which two HPPH moieties were linked to the modified IR820 produced enhanced tumor uptake and tumor contrast in both Colon 26 (a murine Colon carcinoma) and U87 (a human glioblastoma) cell lines. The long-term PDT efficacy (cure) of this conjugate in BALB/c mice...

Apoptosis of HeLa cells induced by a new targeting photosensitizer-based PDT via a mitochondrial pathway and ER stress

Li, Donghong; Li, Lei; Li, Pengxi; Li, Yi; Chen, Xiangyun
Fonte: Dove Medical Press Publicador: Dove Medical Press
Tipo: Artigo de Revista Científica
Publicado em 07/04/2015 EN
Relevância na Pesquisa
27.32%
Photodynamic therapy (PDT) is emerging as a viable treatment for many cancers. To decrease the cutaneous photosensitivity induced by PDT, many attempts have been made to search for a targeting photosensitizer; however, few reports describe the molecular mechanism of PDT mediated by this type of targeting photosensitizer. The present study aimed to investigate the molecular mechanism of PDT induced by a new targeting photosensitizer (PS I), reported previously by us, on HeLa cells. Apoptosis is the primary mode of HeLa cell death in our system, and apoptosis occurs in a manner dependent on concentration, irradiation dose, and drug–light intervals. After endocytosis mediated by the folate receptor, PS I was primarily localized to the mitochondria and the endoplasmic reticulum (ER) of HeLa cells. PS I PDT resulted in rapid increases in intracellular reactive oxygen species (ROS) production and Ca2+ concentration, both of which reached a peak nearly simultaneously at 15 minutes, followed by the loss of mitochondrial membrane potential at 30 minutes, release of cytochrome c from mitochondria into the cytoplasm, downregulation of Bcl-2 expression, and upregulation of Bax expression. Meanwhile, activation of caspase-3, -9, and -12, as well as induction of C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP78)...

In-vivo outcome study of HPPH mediated PDT using singlet oxygen explicit dosimetry (SOED)

Penjweini, Rozhin; Kim, Michele M.; Zhu, Timothy C.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 02/03/2015 EN
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27.32%
Type II photodynamic therapy (PDT) is based on the use of photochemical reactions mediated through an interaction between a tumor-selective photosensitizer, photoexcitation with a specific wavelength of light, and production of reactive singlet oxygen. However, the medical application of this technique has been limited due to inaccurate PDT dosimetric methods. The goal of this study is to examine the relationship between outcome (in terms of tumor growth rate) and calculated reacted singlet oxygen concentration ([1O2]rx) after HPPH-mediated PDT to compare with other PDT dose metrics, such as PDT dose or total light fluence. Mice with radiation-induced fibrosarcoma (RIF) tumors were treated with different light fluence and fluence rate conditions. Explicit measurements of photosensitizer drug concentration and tissue optical properties via fluorescence and absorption measurement with a contact probe before and after PDT were taken to then quantify total light fluence, PDT dose, and [1O2]rx based on a macroscopic model of singlet oxygen. In addition, photobleaching of photosenitizer were measured during PDT as a second check of the model. Changes in tumor volume were tracked following treatment and compared to the three calculated dose metrics. The correlations between total light fluence...

Técnicas terapéuticas basadas en la utilización de luz visible; Therapeutic techniques based on the use of visible light

Cossío Tejido, Santiago de
Fonte: Universidade de Cantabria Publicador: Universidade de Cantabria
Tipo: Trabalho de Conclusão de Curso
SPA
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This article reviews different therapeutic strategies, which have in common the application of visible light to irradiate and thus activate photosensible substances, (PSs) of different nature, previously administered to the patients and distributed throughout their body. These therapies are: photodynamic therapy (PDT), photothermal therapy (PTT) and photoimmunotherapy (PIT). The advantage of these kinds of therapies, compared to the classical chemotherapy or radiotherapy, is that allow the possibility of destroying tumor tissue with less damage of the surrounding healthy tissue. Therapeutic effects of these phototherapies depend on the light-dependent activation of the PSs. The activated PSs induce either the local release of oxidative radicals (ROS) and the activation of immune responses (PDT and PIT), or the local generation of heat (PTT). In PIT, monoclonal antibodies (Mabs) are linked to PSs; thus, Mabs act as carriers to drive PSs to the target tissues. PDT also has antimicrobial effects and so is used as an alternative or adjuvant therapy together with antibiotic therapy since bacteria are unlikely to develop resistance to the ROS induced by PDT; furthermore, PDT enhances immune responses against bacterial pathogens. Although it is not yet a therapeutic technique...

Efeito da terapia fotodinâmica (PDT) sobre culturas de Candida sp. e de células epiteliais: estudo in vitro

Marinho, Sandra Aparecida
Fonte: Pontifícia Universidade Católica do Rio Grande do Sul; Porto Alegre Publicador: Pontifícia Universidade Católica do Rio Grande do Sul; Porto Alegre
Tipo: Tese de Doutorado
PORTUGUêS
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O uso indiscriminado de antifúngicos tem acarretado resistência da Candida sp. , o que requer novas alternativas de tratamento para a candidose oral. A aplicação da terapia fotodinâmica (PDT) tem sido investigada na inativação de microrganismos patogênicos ao hospedeiro humano. O presente estudo teve por objetivo avaliar, in vitro, a ação da PDT sobre a viabilidade da Candida sp. e de células epiteliais. Culturas de Candida sp. obtidas a partir da coleta de amostras de 38 pacientes portadores de candidose oral e culturas de células HEp-2 foram submetidas à PDT. Foi empregado o laser diodo fosfeto de índio-gálio-alumínio (InGaAlP) nas dosimetrias de 100 J/cm2, 270 J/cm2 e 450 J/cm2 associado ao fotossensibilizador azul de metileno na concentração de 100 Rg/mL. Após o tratamento, a viabilidade das unidades formadoras de colônias (UFCs) e das células epiteliais foi quantificada. As três dosimetrias empregadas determinaram inativação significativa da Candida sp. (p<0,05). A dosimetria de 450 J/cm2 foi a mais eficaz, inativando 72,42% das UFCs de Candida sp. , seguida pelas dosimetrias de 270 J/cm2 e 100 J/cm2 com inativação média de 45,84% e 22,83% respectivamente. A Candida albicans foi significativamente mais sensível ao tratamento...