In vitro and in vivo photodynamic activities for BAM-SiPc, an unsymmetrical bisamino silicon(IV) phthalocyanine.

Leung, Ching Hei.Thesis (M.Phil.)--Chinese University of Hong Kong, 2007.Includes bibliographical references (leaves 101-110).Abstracts in English and Chinese.Acknowledgements --- p.i摘要（Abstract in Chinese) --- p.iiiAbstract --- p.vList of Abbreviations --- p.viiList of Figures and Tables --- p.ixTable of Content --- p.xiChapter CHAPTER 1 --- IntroductionChapter 1.1 --- History and development of photodynamic therapy --- p.1Chapter 1.2 --- Basic principle of photodynamic therapy: the beauty of the treatment --- p.3Chapter 1.3 --- "Photosensitizers: From discovery, synthesis to modifications" --- p.6Chapter 1.4 --- Enhancement of selective retention of PS in cancerous tissue --- p.10Chapter 1.5 --- Development of silicon (IV) phthalocyanine derivatives --- p.14Chapter 1.6 --- Death mechanisms in photodynamic therapy --- p.17Chapter 1.7 --- Objectives of the present study --- p.18Chapter CHAPTER 2 --- Materials and MethodsChapter 2.1 --- Synthesis of BAM-SiPc --- p.20Chapter 2.2 --- Preparation of BAM-SiPc solution for photodynamic treatment --- p.20Chapter 2.3 --- Cell line and culture conditions --- p.21Chapter 2.4 --- Animal tumor model --- p.23Chapter 2.5 --- PDT laser source --- p.23Chapter 2.6 --- In vitro photodynamic activity assay --- p.23Chapter 2.6.1 --- Preparation of cells for photodynamic treatmentChapter 2.6.2 --- In vitro photodynamic treatmentChapter 2.6.3 --- Cell viability assayChapter 2.7 --- "Determination of reactive oxygen species production by 2',7'- dichlorofluorescein diacetate (DCFDA) assay" --- p.28Chapter 2.8 --- Analysis of cell cycle arrest --- p.28Chapter 2.9 --- Biodistribution of BAM-SiPc --- p.29Chapter 2.10 --- In vivo photodynamic treatment --- p.30Chapter 2.11 --- Assay for plasma enzyme activities --- p.30Chapter 2.12 --- Determination of cellular uptake of BAM-SiPc --- p.31Chapter 2.13 --- Metabolism of BAM-SiPc --- p.31Chapter 2.14 --- Histochemical staining --- p.32Chapter 2.14.1 --- Preparation of paraffin-embedded tissue sectionChapter 2.14.2 --- Haematoxylin and Eosin (H & E) stainingChapter 2.14.3 --- Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assayChapter 2.15 --- Conjugation of BAM-SiPc with LDL --- p.34Chapter 2.15.1 --- Analysis of the phototoxicity and cellular uptake of BAM- SiPc in the presence of LDLChapter 2.15.2 --- Gel filtration analysis of the mixture of LDL and BAM- SiPcChapter 2.16 --- Statistical analysis --- p.35Chapter CHAPTER 3 --- ResultsChapter 3.1 --- In vitro photodynamic activity assays --- p.36Chapter 3.2 --- Tissue distribution of BAM-SiPc in HepG2- bearing nude mice --- p.39Chapter 3.3 --- Anti-tumor activities of in vivo PDT with BAM-SiPc --- p.42Chapter 3.3.1 --- In vivo effect of PDT treatment with BAM-SiPc on HepG2 and HT29 tumor growthChapter 3.3.2 --- Dosage effect on anti-tumor activities by BAM-SiPc mediated PDTChapter 3.4 --- Analysis of intrinsic toxicity induced by BAM-SiPc mediated PDT --- p.48Chapter 3.4.1 --- H & E staining of liver sections of nude mice after in vivo PDTChapter 3.4.2 --- Plasma enzyme activity assays of PDT treated miceChapter 3.5 --- BAM-SiPc metabolism in in vitro culture cells and liver homogenate --- p.53Chapter 3.5.1 --- Cellular uptake of BAM-SiPcChapter 3.5.2 --- BAM-SiPc metabolism in cultured normal liver cells and cancer cellsChapter 3.5.3 --- BAM-SiPc metabolism by mice liver homogenateChapter 3.6 --- Death mechanism induced by BAM-SiPc mediated PDT --- p.62Chapter 3.6.1 --- Events related to cell death induced by in vitro BAM-SiPc mediated PDTChapter 3.6.2 --- Death mechanism exerted by in vivo BAM-SiPc mediated PDTChapter 3.7 --- Effect on phototoxicity of BAM-SiPc in the presence of LDL --- p.70Chapter 3.7.1 --- Effect on phototoxicity of BAM-SiPc after mixing BAM- SiPc with LDLChapter 3.7.2 --- Gel filtration for analysis of the LDL-BAM-SiPc mixtureChapter CHAPTER 4 --- DiscussionChapter 4.1 --- Anti-cancer effect of BAM-SiPc on different cancer cell lines --- p.76Chapter 4.2 --- Tissue distribution of BAM-SiPc in HepG2 bearing nude mice --- p.77Chapter 4.3 --- In vivo effect of BAM-SiPc mediated PDT on HepG2 and HT29 tumor growth --- p.80Chapter 4.4 --- Analysis of the safety of using BAM-SiPc as a potential agent in PDT --- p.83Chapter 4.5 --- Metabolism of BAM-SiPc --- p.84Chapter 4.6 --- Mechanism of the apoptosis triggered by BAM-SiPc mediated PDT --- p.88Chapter 4.7 --- Death mechanism induced by in vivo PDT with BAM-SiPc --- p.93Chapter 4.8 --- Phototoxicity of BAM-SiPc in the presence of LDL --- p.94Chapter CHAPTER 5 --- Conclusion and Future perspectiveChapter 5.1 --- Conclusion --- p.97Chapter 5.2 --- Future perspective --- p.98Reference