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Chemical aspects of mitochondrial targeting in photodynamic therapy /Bartlett, Jeremy A. January 2002 (has links)
Thesis (Ph. D.)--University of Wisconsin--Madison, 2000. / Includes bibliographical references (leaves 213-223). Also available on Internet.
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Effects of relative humidity on the fluorescence of uranine (disodium fluorescein)Talbot, Collin January 2009 (has links) (PDF)
Thesis--University of Oklahoma. / Bibliography: leaves 62-63.
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Efeito de diferentes protocolos de terapia fotodinâmica antimicrobiana na eliminação de Aggregatibacter actinomycetemcomitans in vitro / Effect of different protocols of antimicrobial photodynamic therapy on elimination of Aggregatibacter actinomycetemcomitans in vitroValle, Luisa Andrade 04 April 2016 (has links)
O tratamento da doença periodontal consiste na remoção mecânica do biofilme, sendo que terapias complementares como a terapia fotodinâmica antimicrobiana (aPDT) podem melhorar os resultados obtidos. Este trabalho avaliou in vitro o efeito dos corantes azul de toluidina e azul de metileno com distintos parâmetros de laser (70; 100mW) e LED em Aggregatibacter actinomycetemcomitans (A.a) em suspensão. O primeiro experimento avaliou efeito bactericida de diferentes concentrações dos dois corantes sozinhos (0,05; 0,1; 0,5, 1,0; 2,0; 5,0; 10 mg/ml). O segundo foi dividido nos seguintes grupos: controles positivo e negativo (gentamicina), grupos somente com luz aplicada, grupos com três concentrações (0,05; 0,1; 10 mg/ml) de corante sozinhos ou associados ao laser de baixa intensidade (660 nm; 2,91 e 4,16 W/cm2; 70 e 100mW; 45 J/cm2; 0,024 cm2; 12 e 18s) e LED (627 ± 10 nm; 150mW/cm2; 10,5 mW; 20 J/cm2; 0,07cm2; 123s). Os dados foram analisados pelo teste ANOVA complementado por Tukey (p<0,05). Os resultados demonstraram que ambos os corantes na concentração de 10 mg/ml sozinhos ou associados com laser (ambas as potências) ou LED causaram 100 % de morte bacteriana semelhante ao controle negativo (p>0,05). Com isso, pode-se concluir que aPDT pode eliminar o A.a. de forma dependente da concentração do corante. / The main treatment of periodontal disease is the mechanical removal of biofilm. Adjuvant therapies as antimicrobial photodynamic therapy (aPDT) may offer better results. The aim of this in vitro study was to evaluate the effect of toluidine and methylene blue dyes, associated to red laser (70; 100mW) and LED on elimination of a suspension of Aggregatibacter actinomycetemcomitans (A.a). A first test evaluated the bactericidal effect of various concentrations of both dyes (0.05; 0.1; 0.5, 1.0; 2.0; 5.0, 10 mg/ml) in absence of light. In the second test, the experimental groups consisted of positive and negative (gentamicin) controls, groups with three concentrations (0.05; 0.1,10 mg/ml) of dyes alone of associated to low level laser (660 nm; 2.91 and 4.16 W/cm2; 70 and 100mW; 45 J/cm2; 0.024 cm2; 12 and 18s) and LED (627 ± 10 nm; 150mW/cm2; 10.5 mW; 20 J/cm2; 0.07cm2; 123s). Data were analyzed by ANOVA complemented by Tukeys test (p<0.05). The results showed that both dyes, with 10 mg/ml, alone or associated to laser and LED caused 100% of death as the negative control (p>0.05). It can be concluded that aPDT is capable of eliminate A.a depending of the dye concentration.
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Photodynamic inactivation of Candida albicans by BAM-SiPc.January 2008 (has links)
So, Cheung Wai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 106-117). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.iii / 摘要 --- p.v / List of Abbreviations --- p.vii / List of Figures --- p.viii / List of Tables --- p.x / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Candida albicans and candidiasis / Chapter 1.1.1 --- Historical background --- p.1 / Chapter 1.1.2 --- C. albicans infections --- p.2 / Chapter 1.1.3 --- Current challenges in the treatment of C. albicans --- p.3 / Chapter 1.2 --- Photodynamic therapy --- p.11 / Chapter 1.2.1 --- Historical aspects and development --- p.11 / Chapter 1.2.2 --- Basic principle of photodynamic therapy --- p.13 / Chapter 1.2.3 --- Light applicator --- p.16 / Chapter 1.2.4 --- Generations of photosensitizer --- p.17 / Chapter 1.2.5 --- Characteristics of phthalocyanines --- p.20 / Chapter 1.2.6 --- Photodynamic antimicrobial chemotherapy (PACT) --- p.22 / Chapter 1.3 --- Aim of present study --- p.24 / Chapter Chapter 2 --- Materials and Methods / Chapter 2.1 --- Synthesis of BAM-SiPc --- p.27 / Chapter 2.2 --- Preparation of BAM-SiPc solution --- p.27 / Chapter 2.3 --- Yeast strains and culture conditions --- p.28 / Chapter 2.4 --- Light source --- p.29 / Chapter 2.5 --- Assays of PDT with planktonic C. albicans / Chapter 2.5.1 --- Photodynamic treatment on planktonic cells --- p.30 / Chapter 2.5.2 --- Clonogenic assay --- p.32 / Chapter 2.5.3 --- Cellular uptake of BAM-SiPc --- p.32 / Chapter 2.5.4 --- Distribution of BAM-SiPc in planktonic cells / Chapter 2.5.4.1 --- Fluorescence microscopic analyses --- p.33 / Chapter 2.5.4.2 --- Confocal laser scanning microscopic (CLSM) analyses --- p.34 / Chapter 2.5.5 --- Determination of ROS level in planktonic cells --- p.34 / Chapter 2.5.6 --- Distribution of ROS in planktonic cells --- p.35 / Chapter 2.5.7 --- Effect of ROS inhibitors --- p.35 / Chapter 2.5.8 --- Membrane integrity assay --- p.36 / Chapter 2.6 --- Assays of PDT with C. albicans biofilm / Chapter 2.6.1 --- Biofilm formation --- p.37 / Chapter 2.6.2 --- Photodynamic treatment on C. albicans biofilm --- p.38 / Chapter 2.6.3 --- Viability assays / Chapter 2.6.3.1 --- XTT reduction assay --- p.38 / Chapter 2.6.3.2 --- Molecular probes staining --- p.40 / Chapter 2.6.4 --- Determination of ROS level in biofilm --- p.41 / Chapter 2.6.5 --- Distribution of BAM-SiPc in biofilm --- p.41 / Chapter 2.6.6 --- Photodynamic treatment on C. albicans from resuspended biofilm --- p.42 / Chapter 2.7 --- Statistical analysis --- p.42 / Chapter Chapter 3 --- Results / Chapter 3.1 --- BAM-SiPc mediated PDT on planktonic C. albicans / Chapter 3.1.1 --- Antifungal effect of BAM-SiPc on C. albicans / Chapter 3.1.1.1 --- PDT activities on different strains of C. albicans --- p.43 / Chapter 3.1.1.2 --- Effect of different densities of cells --- p.47 / Chapter 3.1.1.3 --- Effect of a washing step before illumination --- p.47 / Chapter 3.1.2 --- Optimization of PDT conditions with BAM-SiPc on C. albicans / Chapter 3.1.2.1 --- Time course study --- p.50 / Chapter 3.1.2.2 --- Light dose study --- p.50 / Chapter 3.1.3 --- Uptake of BAM-SiPc --- p.53 / Chapter 3.1.4 --- Distribution of BAM-SiPc in the planktonic cells / Chapter 3.1.4.1 --- Analysis with fluorescence microscopy --- p.56 / Chapter 3.1.4.2 --- Analysis with CLSM --- p.56 / Chapter 3.1.5 --- ROS production upon PDT treatment / Chapter 3.1.5.1 --- ROS level in the planktonic cells --- p.59 / Chapter 3.1.5.2 --- Distribution of ROS production --- p.61 / Chapter 3.1.5.3 --- Effect of different ROS inhibitors on BAM-SiPc's potency --- p.64 / Chapter 3.1.6 --- Membrane integrity --- p.66 / Chapter 3.2 --- BAM-SiPc mediated PDT on C. albicans biofilm / Chapter 3.2.1 --- Establishment of the biofilm model with 192887g --- p.69 / Chapter 3.2.2 --- Photodynamic treatment on 192887g biofilm / Chapter 3.2.2.1 --- Viability assay - XTT assay --- p.72 / Chapter 3.2.2.2 --- Viability assay ´ؤ LIVE/DEAD BacLight Bacterial Viability kit --- p.72 / Chapter 3.2.3 --- ROS level in the biofilm after PDT treatment --- p.75 / Chapter 3.2.4 --- Distribution of BAM-SiPc in the biofilm --- p.75 / Chapter 3.2.5 --- Photodynamic treatment on C. albicans from resuspended biofilm --- p.79 / Chapter Chapter 4 --- Discussion --- p.81 / Chapter 4.1 --- Antifungal effect of BAM-SiPc on the planktonic C. albicans --- p.81 / Chapter 4.2 --- Effects of different conditions on the photodynamic treatment with BAM- SiPc --- p.83 / Chapter 4.3 --- Mechanistic study of the antifungal effect of BAM-SiPc --- p.86 / Chapter 4.3.1 --- Interaction between BAM-SiPc and C. albicans --- p.86 / Chapter 4.3.2 --- ROS as mediator of cell damage --- p.89 / Chapter 4.3.3 --- Analysis of membrane integrity upon photodynamic treatment --- p.91 / Chapter 4.4 --- Establishment of the biofilm model of C. albicans --- p.92 / Chapter 4.5 --- In vitro effect of BAM-SiPc mediated PDT on C. albicans biofilm --- p.95 / Chapter Chapter 5 --- Conclusion and Future Perspectives / Chapter 5.1 --- Conclusion --- p.101 / Chapter 5.2 --- Future perspectives --- p.102 / References --- p.106
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Hidrogéis como sistema de liberação de fotossensibilizador para terapia fotodinâmica contra Cutibacterium (Propionibacterium) acnes /Frade, Maria Lucia. January 2018 (has links)
Orientador: Carla Raquel Fontana / Coorientador: Marlus Chorilli / Banca: Ana Claudia Pavarina / Banca: Natalia Mayumi Inada / Resumo: A acne vulgar é uma das dermatoses mais frequentes em jovens e a infecção causada pela bactéria Cutibacterium acnes (antigo Propionibacterium acnes) tem importante papel na patogênese da acne. Existem várias opções de tratamento que variam de acordo com a gravidade da doença, porém são associados com reações indesejadas e resistência aos antimicrobianos. A terapia fotodinâmica antimicrobiana (TFDa) então é proposta como tratamento alternativo para inativar C. acnes juntamente com a incorporação do fotossensibilizador (FS) em uma formulação tópica para otimizar a terapia. Este trabalho objetivou avaliar a eficácia in vitro da TFDa mediada pelo azul de metileno (AM) incorporado em hidrogel de quitosana e poloxamer (HG-AM) contra C. acnes em fase planctônica e biofilme. A viabilidade celular após TFDa foi avaliada através da quantificação das colônias formadas por mililitro de amostra (UFC/mL). Para caracterizar estruturalmente os HGs foram realizadas as análises oscilatórias e de comportamento de fluxo em reômetro de estresse controlado com geometria placa-cone e a bioadesão em pele de orelha de porco utilizando um texturômetro. A análise estatística dos dados feita foi a Análise de Variância (one way ANOVA) com pós-teste de Tukey. Os resultados deste estudo mostrou que a TFDa contra C. acnes foi eficaz utilizando HG-AM em fase plactônica. A concentração bactericida mínima foi de 12,5 µg/mL associada a uma fluência de 90 J/cm2. O biofilme de C. acnes não foi totalmente eliminad... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Acne vulgaris is one of the most frequent dermatosis in young people and the infection caused by the bacteria Cutibacterium acnes (formerly Propionibacterium acnes) plays an important role in the pathogenesis of acne. There are several treatments options that vary according to the severity of the disease, but are associated with unwanted reactions and antimicrobial resistance. Antimicrobial photodynamic therapy (aPDT) is then proposed as an alternative treatment to inactivate C. acnes together with the incorporation of the photosensitizer (PS) into a topical formulation to optimize therapy. This work aimed to evaluate the in vitro efficacy of methylene blue (MB) mediated TFDa incorporated in chitosan and poloxamer (HG-MB) hydrogels against planktonic and biofilm C. acnes. Cell viability after aPDT was evaluated by quantifying the colonies formed per milliliter of sample (CFU / mL). To characterize structurally the HG were performed the oscillatory and behavior of flow in a controlled stress rheometer with cone-plate geometry and bioadhesion in pig ear skin using a texture analyser. The statistical analysis of the data was the Analysis of Variance (one way ANOVA) with post-test of Tukey. The results of this study showed that aPDT was effective using HG-MB in planktonic phase. The minimum bactericidal concentration was 12.5 μg/mL associated with a fluence of 90 J/cm2 . The C. acnes biofilm was not totally eliminated by the aPDT with HG-MB under the conditions tested. The maximum microbial reduction achieved with HG-MB was 1.9 log10 with 75 μg/mL of the PS using 150 J/cm2 and 30 minutes biofilm incubation with HG-MB. HG at 0.25% of chitosan (HG1) was adequate for application to the skin surface because higher concentrations... (Complete abstract click electronic access below) / Mestre
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Efeito de diferentes protocolos de terapia fotodinâmica antimicrobiana na eliminação de Aggregatibacter actinomycetemcomitans in vitro / Effect of different protocols of antimicrobial photodynamic therapy on elimination of Aggregatibacter actinomycetemcomitans in vitroLuisa Andrade Valle 04 April 2016 (has links)
O tratamento da doença periodontal consiste na remoção mecânica do biofilme, sendo que terapias complementares como a terapia fotodinâmica antimicrobiana (aPDT) podem melhorar os resultados obtidos. Este trabalho avaliou in vitro o efeito dos corantes azul de toluidina e azul de metileno com distintos parâmetros de laser (70; 100mW) e LED em Aggregatibacter actinomycetemcomitans (A.a) em suspensão. O primeiro experimento avaliou efeito bactericida de diferentes concentrações dos dois corantes sozinhos (0,05; 0,1; 0,5, 1,0; 2,0; 5,0; 10 mg/ml). O segundo foi dividido nos seguintes grupos: controles positivo e negativo (gentamicina), grupos somente com luz aplicada, grupos com três concentrações (0,05; 0,1; 10 mg/ml) de corante sozinhos ou associados ao laser de baixa intensidade (660 nm; 2,91 e 4,16 W/cm2; 70 e 100mW; 45 J/cm2; 0,024 cm2; 12 e 18s) e LED (627 ± 10 nm; 150mW/cm2; 10,5 mW; 20 J/cm2; 0,07cm2; 123s). Os dados foram analisados pelo teste ANOVA complementado por Tukey (p<0,05). Os resultados demonstraram que ambos os corantes na concentração de 10 mg/ml sozinhos ou associados com laser (ambas as potências) ou LED causaram 100 % de morte bacteriana semelhante ao controle negativo (p>0,05). Com isso, pode-se concluir que aPDT pode eliminar o A.a. de forma dependente da concentração do corante. / The main treatment of periodontal disease is the mechanical removal of biofilm. Adjuvant therapies as antimicrobial photodynamic therapy (aPDT) may offer better results. The aim of this in vitro study was to evaluate the effect of toluidine and methylene blue dyes, associated to red laser (70; 100mW) and LED on elimination of a suspension of Aggregatibacter actinomycetemcomitans (A.a). A first test evaluated the bactericidal effect of various concentrations of both dyes (0.05; 0.1; 0.5, 1.0; 2.0; 5.0, 10 mg/ml) in absence of light. In the second test, the experimental groups consisted of positive and negative (gentamicin) controls, groups with three concentrations (0.05; 0.1,10 mg/ml) of dyes alone of associated to low level laser (660 nm; 2.91 and 4.16 W/cm2; 70 and 100mW; 45 J/cm2; 0.024 cm2; 12 and 18s) and LED (627 ± 10 nm; 150mW/cm2; 10.5 mW; 20 J/cm2; 0.07cm2; 123s). Data were analyzed by ANOVA complemented by Tukeys test (p<0.05). The results showed that both dyes, with 10 mg/ml, alone or associated to laser and LED caused 100% of death as the negative control (p>0.05). It can be concluded that aPDT is capable of eliminate A.a depending of the dye concentration.
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Terapia Fotodinâmica Antimicrobiana com Utilização da Clorina-e6 sobre Biofilme Periodontopatogênico /Carvalho, Gabriel Garcia de. January 2020 (has links)
Orientador: Daniela Leal Zandim-Barcelos / Resumo: A resistência bacteriana é uma ameaça real alertada pela OMS. A terapia fotodinâmica antimicrobiana (TFDA) pode ser uma das soluções para superar este desafio, uma vez que já demonstra ação antimicrobiana frente a inúmeros patógenos. A clorina-e6 (Ce6) provou ser um fotossensibilizador (FS) com potente efeito quando irradiada pela luz vermelha, contra diferentes biofilmes. No entanto, o principal pico de absorção deste FS está no espectro visível de luz azul, ainda insuficientemente investigado. Este estudo teve como objetivo avaliar o efeito da TFDA com utilização da Ce6 irradiada a 450 e 660 nm contra biofilmes relacionados à doença periodontal. Biofilmes monoespécie de Streptococcus oralis, Fusobacterium nucleatum, Porphyromonas gingivalis e Aggregatibacter actinomycetemcomitans foram desenvolvidos em condições adequadas por cinco dias. A TFDA foi realizada em diferentes concentrações de fotossensibilizador (100 e 200 µM) e comprimentos de onda de luz (450 e 660 nm), e comparada ao controle negativo (DMSO a 1%) e positivo (clorexidina a 0,2%) por análise de unidades formadoras de colônias (UFC) e microscopia confocal. O uso de luz e FS também foram testados individualmente. A maior redução bacteriana foi observada no grupo em que a TFDA foi realizada com utilização da Ce6 a 200 µM e aplicação de luz azul para todas as cepas (redução de 4,01 log10 para A. actinomycetemcomitans e redução total para P. gingivalis e S. oralis), exceto para F. nucleatum, onde o melhor resultado... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre
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Development of smart photosensitizers for targeted photodynamic therapy. / CUHK electronic theses & dissertations collectionJanuary 2012 (has links)
本論文報導了幾個系列的新型鋅酞菁配合物以及氟硼二吡咯染料的合成與表徵。 這些精心設計的化合物可作為高效的和選擇性的光敏劑應用於靶向性光動力療法和細菌的光動力失活。 / 第一章概述了光動力療法,包括歷史發展、光物理和生物機制及其臨床應用現狀。 重點介紹了用於靶向性光動力療法的第三代光敏劑,其中包括基於靶向性配體、納米載體的光敏劑以及可激活的光敏劑。 另外,本章還簡單介紹了用於抗菌光動力療法的光敏劑。 / 第二章報導了一種新型的由細胞核定位的短肽共軛修飾的鋅酞菁配合物的合成與表徵。 此短肽分子的氨基酸序列為:Gly-Gly-Pro-Lys-Lys-Lys-Arg-Lys-Val。 我們研究了該化合物的光物理性質、聚集行為以及離體光動力活性,同時與其非肽共軛修飾的化合物進行了詳細的比較。 利用HT29人結腸腺癌細胞,研究發現此多肽共軛修飾的酞菁展示了較高的細胞吸收、更高的細胞內活性氧的產生效率和光毒性。 同時活體實驗證明此化合物增加了酞菁在裸鼠腫瘤的停留時間。 這些結果在本章中均進行了詳細的報導。 / 第三章敘述了另一種多肽共軛修飾的鋅酞菁化合物的製備和光物理性質。 這個多肽包含了一個環狀的氨基酸序列,即 Arg-Gly-Asp-D-Phe-Lys,此多肽被認為能以腫瘤相關的血管新生時的高表達的跨膜受體(如 α[subscript v]β₃ 整合素)為靶向。 利用 α[subscript v]β₃ 整合素高表達的 U87-MG 人惡性膠質瘤細胞,我們研究了這個化合物的細胞吸收、細胞內活性氧的產生、離體光動力活性以及亞細胞定位。 同時,用 α[subscript v]β₃ 整合素低表達的 MCF-7 人乳腺癌細胞作為對照。 / 通常,腫瘤細胞外的pH值比正常細胞組織的低,因此,我們合成一個由酸敏感的縮醛鍵連接的酞菁二聚體。 此二聚體會發生自身淬滅且對pH有響應。 通過電子吸收和熒光光譜, 我們詳細地研究了這個化合物在不同酸性條件下的光物理性質和斷開動力學。 由於酞菁環具有強的二聚化趨勢,這個二聚體能自身淬滅,因而呈現“失活狀態。 通過降低檸檬酸緩衝液的pH值,這個化合物的乙縮醛鍵能優先斷開,並且斷開的速率隨pH值的降低而增加。 兩個酞菁環的分開增強了熒光強度和單態氧的產生。 這個二聚光敏劑還能在 HT29 細胞內被激活,從而產生較強的細胞內熒光。 相比之下,由乙二醇鏈連接的類似物基本上沒有熒光發射。 同時,這個可斷開的二聚物對HT29細胞光毒性也比不可斷開的類似物高(半致死量:IC₅₀ = 0.35 vs. 0.59 μM)。 第四章對這些結果進行了詳細的報導。 / 在第五章中,我們報導了兩種以腫瘤靶向配體葉酸共軛修飾的二(苯乙烯基)-氟硼二吡咯衍生物的合成、光譜表徵以及光物理性質。 在這兩個化合物中,葉酸和二(苯乙烯基)-氟硼二吡咯是通過不同長度的乙二醇鏈連接的。 我們研究了這兩個化合物的鏈長對KB人鼻咽癌細胞和MCF-7細胞的吸收和離體光動力活性的影響。 前者能高表達葉酸受體,而後者作為低葉酸受體表達的一個對照。 與MCF-7細胞相比,兩個化合物都展示了對KB細胞較高的吸收和光毒性(半致死量:IC₅₀ = 0.062 vs. 2.56 μM 和0.177 vs. 0.995 μM)。 此外,具有較長鏈的化合物優先定位在溶酶體中,而較短鏈的那個化合物則較多停留在細胞的內質網。 / 第六章重點開發了一系列多胺以及不同長度的聚賴氨酸(包括2、4、8個賴氨酸)共軛修飾的鋅酞菁配合物,并用於抗菌光動力療法。 我們報導了它們的合成、光物理性質以及對甲氧西林青霉素敏感的格蘭陽性金黄色釀膿葡萄球菌和格蘭陰性綠膿桿菌的光動力抗菌活性。 其中,三-N-甲基化的酞菁顯示了特別高的效果,在濃度為16 nM時,能降低大於5 log10 的金黄色釀膿葡萄球菌。 / 第七章闡述了前面幾章的實驗部份。 論文的最後附上所有新化合物的核磁共振氫譜和碳譜。 / This thesis describes the synthesis and characterization of several series of novel zinc(II) phthalocyanines and boron dipyrromethenes (BODIPYs), which are carefully designed as efficient and selective photosensitizers for targeted photodynamic therapy (PDT) and photodynamic inactivation of bacteria. / Chapter 1 presents an overview of PDT, including its historical development, photophysial and biological mechanisms, and current research directions. Emphasis is placed on the third-generation photosensitizers for targeted PDT, including targeting ligand-based photosensitizers, nanoparticle-based photosensitizers, and activatable photosensitizers. A brief review of photosensitizers that can be used for antimicrobial PDT is also given. / Chapter 2 reports the synthesis and characterization of a novel zinc(II) phthalocyanine conjugated with a short peptide with a nuclear localization sequence, namely Gly-Gly-Pro-Lys-Lys-Lys-Arg-Lys-Val. The photophysical properties, aggregation behavior, and in vitro photodynamic activity of this compound have been investigated and compared with its non-peptide-conjugated analogue. It has been found that the peptide-conjugated phthalocyanine shows an enhanced cellular uptake, higher efficiency in generating intracellular reactive oxygen species (ROS), higher photocytotoxicity against HT29 human colorectal adenocarcinoma cells, and enhanced tumor-retention property in tumor-bearing nude mice. The results are reported in detail in this chapter. / Chapter 3 describes the preparation and photophysical properties of another analogue conjugated with a peptide containing the cyclic Arg-Gly-Asp-D-Phe-Lys sequence, which is known to target the upregulated transmembrane protein receptors such as α[subscript v]β₃ integrin during angiogenesis. The cellular uptake, intracellular ROS generation, in vitro photodynamic activity, and subcellular localization of this conjugate have been investigated against U87-MG human glioblastoma cells, which have a high expression of α[subscript v]β₃ integrin. MCF-7 human breast adenocarcinoma cells, which have a low expression of α[subscript v]β₃ integrin, have been used as a negative control. / On the base that the extracellular pH in tumors is generally lower than that in normal tissues, we have developed a pH-responsive self-quenched phthalocyanine dimer connected with an acid-sensitive ketal linker. The basic photophysical properties of this compound and its cleavage kinetics upon exposure to different acidic conditions have been extensively studied by electronic absorption and fluorescence spectroscopy. Owing to the strong dimerization tendency of the phthalocyanine ring, this dimer is self-quenched and in the "OFF" state. By lowering the pH (< 6.5) in citrate buffer solutions, the linker is preferentially cleaved, and the rate of cleavage increases as the pH decreases. The separation of the phthalocyanine moieties leads to enhancement in fluorescence intensity and singlet oxygen production. This dimeric photosensitizer can also be activated inside HT29 cells causing strong intracellular fluorescence. By contrast, the fluorescence is hardly observed for the non-cleavable ethylene glycol-linked analogue. The photocytotoxicity of the cleavable dimer is also higher than that of the non-cleavable counterpart (IC₅₀ = 0.35 vs. 0.59 μM). The results are reported in detail in Chapter 4. / In Chapter 5, we describe the synthesis, characterization, and photophysical properties of two distyryl BODIPY derivatives conjugated with a folic acid as a tumor-targeting ligand via an ethylene glycol spacer with different chain length. The effects of the chain length on the cellular uptake and in vitro photodynamic activities of these compounds have been examined against KB human nasopharyngeal epidermal carcinoma cells and MCF-7 cells. The former are known to have a high expression of folate receptors, while the latter have been used as a negative control. Both compounds show enhanced cellular uptake and higher photocytotoxicity toward KB cells when compared with MCF-7 cells (IC₅₀ = 0.062 vs. 2.56 μM and 0.177 vs. 0.995 μM). The conjugate with a longer spacer shows preferential localization in the lysosomes, while the analogue with a shorter linker accumulates in the endoplasmic reticulum of the cells. / Chapter 6 focuses on the development of a series of zinc(II) phthalocyanines substituted with a polyamine moiety or a polylysine chain containing 2, 4, or 8 lysine units for antimicrobial PDT. Their synthesis, photophysical properties, and photodynamic antimicrobial activities against Gram (+) methicillin-sensitive Staphylococcus aureus and Gram (-) Pseudomonas aeruginosa are reported. The tri-N-methylated phthalocyanine is particularly potent showing a more than 5 log₁₀ reduction of the Staphylococcus aureus at 16 nM. / Chapter 7 gives the experimental details for the work described in the preceding chapters. ¹H and ¹³C{¹H} NMR of all the new compounds are given in the Appendix. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Ke, Meirong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 159-176). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Abstract --- p.i / Abstract (in Chinese) --- p.v / Acknowledgment --- p.viii / Table of Contents --- p.xi / List of Figures --- p.xvi / List of Schemes --- p.xxiv / List of Tables --- p.xxv / Abbreviations --- p.xxvi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- General Introduction of Photodynamic Therapy --- p.1 / Chapter 1.2 --- Mechanisms of Photodynamic Therapy --- p.2 / Chapter 1.2.1 --- Photophysical Mechanisms --- p.2 / Chapter 1.2.2 --- Biological Mechanisms --- p.4 / Chapter 1.3 --- Clinical Status of Photodynamic Therapy --- p.5 / Chapter 1.4 --- Overview of Photosensitizers --- p.7 / Chapter 1.5 --- Targeted Photodynamic Therapy --- p.13 / Chapter 1.5.1 --- Targeting Ligand-Based Photosensitizers --- p.13 / Chapter 1.5.1.1 --- Synthetic Peptides --- p.13 / Chapter 1.5.1.2 --- Proteins --- p.16 / Chapter 1.5.1.3 --- Aptamers --- p.18 / Chapter 1.5.1.4 --- Folic acid --- p.19 / Chapter 1.5.1.5 --- Other Biological Ligands --- p.20 / Chapter 1.5.2 --- Nanoparticle-Based Photosensitizers --- p.20 / Chapter 1.5.2.1 --- Biodegradable Nanoparticle-Based Photosensitizers --- p.21 / Chapter 1.5.2.2 --- Non-Biodegradable Nanoparticle-Based Photosensitizers --- p.23 / Chapter 1.5.3 --- Activatable Photosensitizers --- p.25 / Chapter 1.5.3.1 --- Environment-Activated Photosensitizers --- p.26 / Chapter 1.5.3.2 --- Enzyme-Activated Photosensitizers --- p.27 / Chapter 1.5.3.3 --- Nucleic Acid-Activated Photosensitizers --- p.29 / Chapter 1.6 --- Antimicrobial Photodynamic Therapy --- p.32 / Chapter 1.6.1 --- General Introduction --- p.32 / Chapter 1.6.2 --- Photosensitizers for Antimicrobial Photodynamic Therapy --- p.34 / Chapter Chapter 2 --- A Phthalocyanine-Peptide Conjugate with High in vitro Photodynamic Activity and Enhanced in vivo Tumor-Retention Property --- p.36 / Chapter 2.1 --- Introduction --- p.36 / Chapter 2.2 --- Results and Discussion --- p.37 / Chapter 2.2.1 --- Molecular Design and Synthesis --- p.37 / Chapter 2.2.2 --- Electronic Absorption and Photophysical Properties --- p.42 / Chapter 2.2.3 --- In Vitro Photodynamic Activities --- p.44 / Chapter 2.2.4 --- In Vivo Studies --- p.50 / Chapter 2.3 --- Conclusion --- p.52 / Chapter Chapter 3 --- Synthesis, Characterization, and Photodynamic Activity of a cylic RGD-Conjugated Phthalocyanine --- p.53 / Chapter 3.1 --- Introduction --- p.53 / Chapter 3.2 --- Results and Discussion --- p.54 / Chapter 3.2.1 --- Molecular Design and Synthesis --- p.54 / Chapter 3.2.2 --- Electronic Absorption and Photophysical Properties --- p.57 / Chapter 3.2.3 --- In Vitro Photodynamic Activities --- p.59 / Chapter 3.3 --- Conclusion --- p.67 / Chapter Chapter 4 --- A pH-Responsive Fluorescent Probe and Photosensitizer Based on the Dimerization Property of Phthalocyanines --- p.69 / Chapter 4.1 --- Introduction --- p.69 / Chapter 4.2 --- Results and Discussion --- p.70 / Chapter 4.2.1 --- Synthesis and Characterization --- p.70 / Chapter 4.2.2 --- Electronic Absorption and Photophysical Properties --- p.74 / Chapter 4.2.3 --- In Vitro Studies --- p.80 / Chapter 4.3 --- Conclusion --- p.84 / Chapter Chapter 5 --- Synthesis, Characterization, and Photodynamic Activities of BODIPY-Folate Conjugates --- p.86 / Chapter 5.1 --- Introduction --- p.86 / Chapter 5.2 --- Results and Discussion --- p.87 / Chapter 5.2.1 --- Synthesis and Characterization --- p.87 / Chapter 5.2.2 --- Electronic Absorption and Photophysical Properties --- p.92 / Chapter 5.2.3 --- In Vitro Studies --- p.94 / Chapter 5.3 --- Conclusion --- p.100 / Chapter Chapter 6 --- Synthesis, Characterization, and Antimicrobial Photodynamic Activities of Cationic Phthalocyanines --- p.102 / Chapter 6.1 --- Introduction --- p.102 / Chapter 6.2 --- Results and Discussion --- p.103 / Chapter 6.2.1 --- Synthesis and Characterization --- p.103 / Chapter 6.2.2 --- Electronic Absorption and Photophysical Properties --- p.108 / Chapter 6.2.3 --- In Vitro Photodynamic Antimicrobial Activities --- p.112 / Chapter 6.3 --- Conclusion --- p.114 / Chapter Chapter 7 --- Experimental Section --- p.115 / Chapter 7.1 --- General --- p.115 / Chapter 7.2 --- Synthesis --- p.119 / Chapter 7.2.1 --- Synthesis for Chapter 2 --- p.119 / Chapter 7.2.2 --- Synthesis for Chapter 3 --- p.125 / Chapter 7.2.3 --- Synthesis for Chapter 4 --- p.128 / Chapter 7.2.4 --- Synthesis for Chapter 5 --- p.132 / Chapter 7.2.5 --- Synthesis for Chapter 6 --- p.138 / Chapter 7.3 --- pH-Response Properties of 4.6 and 4.7 in Citrate Buffer Solutions --- p.143 / Chapter 7.4 --- In Vitro Studies --- p.144 / Chapter 7.4.1 --- Cell Lines and Culture Conditions --- p.144 / Chapter 7.4.2 --- Photocytotoxicity Assay --- p.145 / Chapter 7.4.3 --- Photodynamic Antimicrobial Inactivatoin Studies --- p.147 / Chapter 7.4.4 --- Intracellular ROS Measurements --- p.148 / Chapter 7.4.5 --- Cellular Uptake (Determined by Extraction Method) --- p.149 / Chapter 7.4.6 --- Cellular Uptake (Determined by Confocal Microscopy) --- p.150 / Chapter 7.4.7 --- Cellular Uptake (Determined by Flow Cytometry) --- p.152 / Chapter 7.4.8 --- Fluorescence Microscopic Studies --- p.153 / Chapter 7.4.9 --- Subcellular Localization Studies --- p.153 / Chapter 7.4.10 --- pH-Dependent Intracellular Fluorescence Studies --- p.155 / Chapter 7.5 --- In Vivo Imaging and Ex Vivo Organ Biodistribution --- p.156 / Chapter Chapter 8 --- Conclusion and Outlook --- p.157 / References --- p.159 / Chapter Appendix --- NMR Spectra of New Compounds --- p.177
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Avaliação da eficácia da terapia fotodinâmica como adjunto ao tratamento periodontal de pacientes com periodontite agressiva / Evaluation of the photodynamic therapy efficacy in the treatment of patients with agressive periodontitisFlavia Bomfim Garcia 26 February 2010 (has links)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A periodontite agressiva é um processo inflamatório de origem bacteriana mediado pelo sistema imunológico do hospedeiro e é provavelmente a forma mais grave de doença periodontal, apresentando destruição das estruturas tanto de proteção quanto de suporte dentário, num período relativamente rápido, normalmente levando a perda prematura dos elementos dentários e, em alguns casos, terapia antimicrobiana adjunta é necessária em adição à terapia mecânica. O objetivo do presente ensaio clínico randomizado controlado foi avaliar o efeito clínico da terapia fotodinâmica como adjunto ao tratamento periodontal não cirúrgico no tratamento da periodontite agressiva Os seguintes parâmetros clínicos foram avaliados: índice de placa visível, sangramento à sondagem, profundidade de bolsa à sondagem, nível de inserção clínica relativo, envolvimento de furca e mobilidade. Foram selecionados dez pacientes com periodontite agressiva, os quais foram examinados no dia zero e após três meses.O desenho do estudo consistiu em um modelo de boca dividida, onde um hemiarco foi tratado com raspagem e alisamento radicular e terapia fotodinâmica (laser diodo) e o outro apenas com raspagem e alisamento radicular. Três meses após o término do tratamento, os grupos terapêuticos apresentaram resultados semelhantes para todos os parâmetros clínicos avaliados: ambas as terapias tiveram sucesso, como redução de profundidade de bolsa, ganho de nível de inserção clínica relativo, redução de índice de placa visível, redução de sangramento à sondagem, diminuição de envolvimento de furca e diminuição de mobilidade, porém sem diferenças estatisticamente significantes entre elas. Dentro das limitações do presente estudo, os resultados sugerem que a terapia fotodinâmica adjuntamente ao tratamento periodontal não cirúrgico mecânico foi tão eficaz quanto o tratamento periodontal não cirúrgico mecânico sozinho. / Aggressive periodontitis is an inflammatory process of bacterial origin mediated by host immune response and is probably the most serious form of periodontal disease, with destruction of the structures of protection and support, with fast course, often leading to premature loss of the teeth and, in some cases, adjunct antimicrobial therapy is need in addition to mechanical therapy. The aim of this randomized controlled trial was to investigate the clinical effect of photodynamic therapy as an adjunct to nonsurgical periodontal treatment in patients with aggressive periodontitis. The following clinical parameters were evaluated: visible plaque index, bleeding on probing, probing pocket depth, relative attachment level, furcation involvement and mobility. We selected ten patients with aggressive periodontitis, which were examined in the baseline to three months. The study design consisted of a split mouth model, where a quadrant was treated with scaling and root planing and photodynamic therapy (diode laser) and the other only with scaling and root planing. Three months after the end of the treatment, the treatment groups showed similar results for all clinical parameters evaluated: both therapies have been successful and showed reduction of pocket depth, gain of relative attachment level, reduction of visible plaque index, reduction of bleeding on probing, decreased furcation involvement and decreased mobility, but without statistically significant differences between them. Within the limitations of the present study the results suggest that photodynamic therapy adjunct to non-surgical periodontal mechanic treatment was as effective as the non-surgical periodontal mechanic treatment alone.
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Avaliação da influência da terapia fotodinâmica antimicrobiana na alteração de cor da estrutura dentária e de uma resina composta / Influence of antimicrobial photodynamic therapy in the color change of the tooth structure and a resin compositeLorenzetti, Camila Cruz [UNESP] 05 March 2015 (has links) (PDF)
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Previous issue date: 2015-03-05 / O objetivo deste trabalho, dividido em dois estudos, foi avaliar: (1) a influência da terapia fotodinâmica antimicrobiana na alteração de cor da dentina utilizando azul de metileno e curcumina como fotossensibilizadores nas concentrações de 20, 40 e 60 µM e nos tempos de pré-irradiação de 2 e 5 minutos, irradiados com fonte de luz LED; e (2) a influência do mesmo tratamento antimicrobiano com os mesmos fotossensibilizadores, concentrações e tempos de pré-irradiação utilizados no estudo anterior, porém sobre alteração de cor em uma resina composta microhíbrida. No primeiro estudo foram confeccionados 130 espécimes a partir de dentes humanos extraídos, os quais foram seccionados em máquina de cortes Isomet. Após a imersão nos fotossensibilizadores, avaliou-se as alterações de cor através de um espectrofotômetro de colorimetria em quatro momentos: antes do início da imersão nas soluções dos fotossensibilizadores (L0), após imersão nos fotossensibilizadores (L1), após irradiação (L2), após 10 dias (L3), após 30 dias (L4) e após 60 dias (L5). Observou-se uma variação alta das médias de ∆E nos grupos com azul de metileno independentemente da concentração e do tempo de exposição, diminuindo a partir da leitura de 10 dias. Com os grupos com curcumina, houve uma variação inicial sem diferença significativa do controle, mantendo-se próxima a ele nas leituras seguintes. Ambos fotossensibilizadores apresentaram alterações significantes clinicamente em dentina segundo a classificação da ―National Bureau of Standards‖ (NBS), sendo a alteração com a curcumina menor que do azul de metileno. No segundo estudo foram confeccionados 130 espécimes de resina composta microhíbrida (Filtek Z250XT) utilizando uma matriz de aço (10x2mm). Após a confecção dos espécimes, estes foram imersos...(Resumo completo, clicar acesso eletrônico abaixo) / This study, divided in two studies, was to evaluate: (1) the influence of antimicrobial photodynamic therapy in color change dentin using methylene blue and curcumin as photosensitizers in concentrations of 20, 40 and 60 uM and pre irradiation times 2 to 5 minutes, irradiated with a LED light source; and (2) the effect of the same antimicrobial treatment with the same photosensitizers, concentrations and pre-irradiation times used in the previous study, but on color change in a microhybrid composite. In the first study were produced 130 specimens from extracted human teeth, which were cut in Isomet cuts machine. After immersion in the photosensitizers, the color changes were evaluated using a spectrophotometer colorimeter in four stages: before the immersion in solutions of photosensitizers (L0) after immersion in photosensitizers (L1) after irradiation (L2), after 10 days (L3) after 30 days (L4) and 60 days (L5). There was a high variation of ΔE averages of the methylene blue groups independently of the concentration and exposure time, decreasing from a reading of 10 days. With curcumin groups, there was no significant difference initial variation control, remaining next to it in the subsequent readings. Both photosensitizers showed clinically significant changes in dentin according to the classification of ―National Bureau of Standards‖ (NBS), with a lowest change to curcumin that of methylene blue. In the second study were made 130 specimens microhybrid composite resin (Filtek Z250XT) using a steel matrix (10x2mm). After preparation of the specimens, they were immersed in solutions of photosensitizers and subsequently evaluated with a spectrophotometer Colorimetry in the same color reading moments performed in the previous study (initial, after immersion, after light irradiation, after 10, 30 and 60 days). In methylene blue groups was no statistically significant difference... (Complete abstract access below)
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