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M.Tech. / Photodynamic therapy is a treatment that is used for the destruction of certain types of tumours and is emerging as a promising treatment modality in the field of dermatology (Davids et al., 2008). The photochemical interactions of the photosensitizer, light and molecular oxygen producing reactive oxygen species known as ROS, results in damage to organelles within malignant cells and so can lead to tumour destruction (Plaetzer et al., 2008). Melanoma is one of the most common forms of malignancies (Oliveria et al., 2007). Unfortunately, there are limited treatment options available for this disease because chemotherapy and radiation therapy are largely ineffective. Metastatic disease frequently develops even after potentially curative surgery (MacCormack, 2008). Since this metastatic disease is an understudied cancer, and the incidence and mortality is increasing, describing the long term burden of this cancer and identifying factors that contribute to it will facilitate efforts to develop responsive prevention strategies, so that novel therapies such as PDT can be proposed (Oliveria et al., 2007; Pan et al., 2008; Schuitmaker et al., 1996). Numerous worldwide clinical trials have shown that PDT represents an effective and safe modality for various skin disorders, but little research has been done in terms of its effect on malignant melanomas (De Rosa and Bentley, 2000; Kolarova et al., 2008). In order for PDT to be an effective treatment modality it depends on many factors such as the type of photosensitizer utilized its ability to selectively penetrate tumour cells and the duration of the treatment (Robertson et al., 2009). Other important factors include the type of activating light source, its ability to penetrate the desired target and the duration of exposure (Plaetzer et al., 2008). Lastly, the type of target cells and their oxygen status also play an important role in the efficacy iv of PDT (Kolarova et al., 2008). In order for PDT to be completely effective, the resulting damage from the treatment must surpass cellular repair mechanisms and cause direct destruction of cellular pathways through vascular compromise and increase immune response to overcome disease (Pazos and Nader, 2007). Porphyrins are the most studied photosensitizers and their disadvantage is the inability to specifically localize in tumour cells and so they are retained in normal cells for prolonged periods, causing patients to be photosensitive (Braathen et al., 2007). This factor stimulated the development of second generation photosensitizers with improved physical, chemical and spectral properties (Davids et al., 2008). Phthalocyanine compounds are second generation photosensitizers which have shown potential in the PDT treatment of many cancers (Kolarova et al., 2007).

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

Thesis (Ph.D.) OGI School of Science & Engineering at OHSU, March 2008. / Includes bibliographical references (leaves 163 - 169).

The combination of chemotherapy and photodynamic therapy was investigated by synthesis and characterization of octacarboxy phthalocyanine covalent conjugates with platinum complexes. This work presents the synthesis, characterization and photophysicochemical properties of aluminium (diaquaplatinum) octacarboxyphthalocyanine and aluminium (diammine) octacarboxyphthalocyanine. The conjugates were prepared by conjugating aluminium octacarboxy phthalocyanine with potassium tetrachloro platinate to yield aluminium tetrakis and trikis (diaquaplatinum) octacarboxy phthalocyanine. The aluminium octacarboxy phthalocyanine was also conjugated with cis-diamminedichloroplatinum to yield aluminium bis and tris (diaquaplatinum) octacarboxy phthalocyanine. From the characterization of the conjugates it was discovered that the aluminium (diaquaplatinum) octacarboxy phthalocyanine had formed platinum nanoparticles with the Pc acting as a capping agent. The triplet lifetimes decreased with the increasing number of platinum complexesconjugated to the Pc. The heavy atom effect improved the overall photophysicochemical properties.

D.Tech. (Biomedical Technology) / Photodynamic therapy (PDT) is an alternative treatment modality for malignant tumours based on the photodamage to tumour cells through a photochemical reaction (Ahn et al., 2013). PDT utilizes a light sensitive photosensitizer (PS) that selectively localizes in tumour cells and is excited by light of a specific wavelength in the presence of molecular oxygen. The excited PS leads to the generation of singlet oxygen or other reactive oxygen species(ROS) which induces cytotoxic damage to cellular organelles and eventually cell death. Singlet oxygen has a very short life and its generation is controlled by the presence of the PS and the laser light (Senge and Radomski, 2013).The subcellular localization site of the PS plays a vital role in determining the effectiveness and the extent of cellular damage as well as the mechanism involved in cell death. Lung cancer is the leading cause of cancer death worldwide in both males and females, with an estimated 1.4 million deaths each year (American Cancer Society, 2011). Therapeutic modalities used in the treatment of lung cancer such as chemotherapy, radiotherapy and immunotherapy have rarely yielded a good prognosis and effective treatment remains a challenging problem to date. An alternative treatment modality with minimal complications such as PDT needs to be explored. Most in vitro PDT experiments are conducted on monolayer cultures and the cellular environment of these cultures does not correspond to that of in vivo studies. Multicellular tumour spheroids (MCTSs) serves as an important model in cancer research for the evaluation of therapeutic interventions since they mimic different aspects of the human tumour tissue environment.

Orientador: Juliana Campos Junqueira / Banca: Antonio Olavo Cardoso Jorge / Banca: Fernanda Malagutti Tomé / Banca: Renato Araújo Prates / Banca: Raduan Hage / Resumo: Devido ao rápido aumento dos micro-organismos resistentes aos antibióticos e ao desenvolvimento limitado de novos agentes antimicrobianos, as infecções por bactérias Gram-negativas estão se tornando um desafio para os profissionais da saúde e uma ameaça para a saúde pública internacional. O objetivo desse estudo foi avaliar o efeito sinérgico dos antibióticos convencionais associados a terapia fotodinâmica antimicrobiana (PDT) no controle de Acinetobacter baumannii. Para realização desse trabalho, foram obtidos isolados clínicos de A. baumannii do Laboratório de Análises Clínicas Valeclin da cidade de São José dos Campos/SP, identificados pelo método de bioquimismo e submetidos ao teste de difusão em disco para verificar a sensibilidade antimicrobiana. Os isolados selecionados foram transferidos para o ICT/UNESP, onde foi realizado testes para determinação da Concentração Inibitória Mínima aos antibióticos Imipenem e Meropenem seguindo as normas da CLSI. Cepas sensíveis e resistentes aos antibióticos foram avaliadas quanto a sensibilidade in vitro à terapia fotodinâmica antimicrobiana. Além disso, foram testados os efeitos dos antibióticos convencionais, da PDT e da terapia combinada de antibióticos e PDT nas infecções experimentais induzidas em G. mellonella por isolados clínicos de A. baumannii resistentes aos antibióticos. Os resultados das terapias na infecção experimental foram avaliados por meio da curva de sobrevivência das lagartas de G. mellonella. Os dados dos testes in vitro foram submetidos à Análise de Variância e teste de Tukey. Os dados obtidos na curva de sobrevivência de G. mellonella foram analisados pelo método de Log-rank. Em todos os testes, foi considerado nível de significância de 5%. Nos resultados desse estudo, observou-se que o Laboratório Valeclin identificou 1,54% de amostras positivas para A. baumannii entre as 13.715 amostras clínicas analisadas em um período de... / Abstract: Due to the rapid growth of microorganisms resistant to antibiotics and the limited development of new antimicrobial agents, infections by Gramnegative bacteria are becoming a challenge for health professionals and a threat to international public health. The aim of this study was to evaluate the synergistic effect of conventional antibiotics associated with antimicrobial photodynamic therapy (PDT) in control of Acinetobacter baumannii. In order to conduct this project were obtained clinical isolates of A. baumannii at the Clinical Laboratory Valeclin situated in the city of São José dos Campos / SP, identified by bioquimismo method and submitted to disk diffusion test to verify the antimicrobial sensitivity. The selected isolates were transferred to the ICT / UNESP, which were conducted tests to determine the Minimum Inhibitory Concentration to Imipenem and Meropenem antibiotics following the rules of the CLSI. Sensitive and resistant strains to antibiotics were evaluated in vitro sensitivity to antimicrobial photodynamic therapy. Besides, the effects of conventional antibiotics, and combined PDT, and PDT of antibiotics in experimental infections induced in G. mellonella by clinical isolates of A. baumannii resistant to antibiotic therapy were tested. The results of therapies in experimental infection were evaluated by survival curve of worms G. mellonella. Data from in vitro tests were submitted to ANOVA and Tukey test. The data obtained in G. mellonella survival curve were analyzed by log-rank method. In all tests it was considered 5% significance level. The results of this study, it was observed that the Valeclin Laboratory identified 1.54% of positive samples for A. baumannii between the 13,715 clinical specimens analyzed in a period of 8 months. Among the isolates of A. baumannii, 58% were resistant to antibiotic imipenem and meropenem by disk diffusion test. Next, 3 isolates clinical sensitive and 18 isolates resistant to those ... / Doutor

Duan Lei. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references. / Abstracts in English and Chinese. / Abstract --- p.i / Abstract (in Chinese) --- p.iii / Acknowledgement --- p.iv / Table of Contents --- p.v / List of Figures --- p.viii / List of Tables --- p.xii / List of Schemes --- p.xiii / Abbreviations --- p.xvi / Chapter Chapter 1 --- Unsymmetrical Phthalocyanines 一 An Overview / Chapter 1.1 --- Introduction --- p.1 / Chapter 1.2 --- Synthesis of A3B Phthalocyanines --- p.7 / Chapter 1.2.1 --- Statistical Condensation --- p.7 / Chapter 1.2.2 --- The Subphthalocyanine Approach --- p.13 / Chapter 1.2.3 --- Synthesis on Polymer Support --- p.16 / Chapter 1.3 --- Synthesis of A2B2 Phthalocyanines --- p.18 / Chapter 1.3.1 --- Preparation of Cross-Substituted Phthalocyanines (ABAB-type) --- p.19 / Chapter 1.3.2 --- Preparation of ´ب´بAdjacent´ح Phthalocyanines (AABB-type) --- p.21 / Chapter 1.4 --- Objectives of This Thesis --- p.24 / Chapter 1.5 --- References --- p.25 / Chapter Chapter 2 --- "Synthesis, Characterization and in vitro Photodynamic Activities of Mono-Alkoxy and Hydroxy Zinc(II) Phthalocyanines" / Chapter 2.1 --- Introduction --- p.29 / Chapter 2.2 --- "Preparation and Characterization of Unsymmetrical Zinc(II) Phthalocyanines Substituted with a 3,4,5- Tris(dodecyloxy)phenylmethyloxy Group" --- p.30 / Chapter 2.3 --- Preparation and Characterization of Halogenated Unsymmetrical Zinc(II) Phthalocyanines --- p.35 / Chapter 2.4 --- Preparation and Characterization of 2-Hydroxy Zinc(II) Phthalocyanine --- p.44 / Chapter 2.5 --- Introduction of Photodynamic Therapy (PDT) --- p.47 / Chapter 2.6 --- In vitro Photodynamic Activities of 2-Hydroxy Zinc(II) Phthalocyanine --- p.50 / Chapter 2.7 --- Conclusion --- p.52 / Chapter 2.8 --- Experimental Section --- p.52 / Chapter 2.9 --- References --- p.63 / Chapter Chapter 3 --- "Synthesis, Characterization and in vitro Photodynamic Activities of Phthalocyanines Containing N，N-Di- methylaminoethylsulfanyl Substituents" / Chapter 3.1 --- Introduction --- p.66 / Chapter 3.2 --- Preparation and Characterization of Octasubstituted Phthalocyanines --- p.67 / Chapter 3.3 --- Characterization of Disubstituted Amphiphilic Zinc(II) Phthalocyanines --- p.74 / Chapter 3.4 --- In vitro Photodynamic Activities --- p.80 / Chapter 3.5 --- Conclusion --- p.83 / Chapter 3.6 --- References --- p.90

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references.

Thesis (MS)--Montana State University--Bozeman, 2008. / Typescript. Chairperson, Graduate Committee: Jean Starkey. Includes bibliographical references (leaves 70-76).