Photodynamic activity of a glucoconjugated Silicon(IV) phthalocyanine on human colon adenocarcinoma.

• Other Authors: Chan, Man Hung.
• Format: Others
• Language: English; Chinese
• Published: 2009
• Subjects: Colon (Anatomy) > Cancer > Treatment; Adenocarcinoma > Treatment; Photosensitizing compounds > Therapeutic use; Cancer > Photochemotherapy; Colonic Neoplasms > drug therapy; Adenocarcinoma > drug therapy; Photosensitizing Agents > therapeutic use; Photochemotherapy
• Online Access: http://library.cuhk.edu.hk/record=b5896599; http://repository.lib.cuhk.edu.hk/en/item/cuhk-326806

Chan, Man Hung. === Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. === Includes bibliographical references (leaves 111-126). === Abstract also in Chinese. === Examination Committee List --- p.ii === Declaration --- p.iii === Acknowledgements --- p.iv === 摘要（Abstract in Chinese) --- p.vi === Abstract --- p.viii === List of Abbreviations --- p.x === List of Figures and Tables --- p.xii === Table of Content --- p.xiv === Chapter Chapter 1 --- Introduction --- p.1 === Chapter 1.1 --- Background of photodynamic therapy (PDT) --- p.2 === Chapter 1.1.1 --- History of PDT --- p.2 === Chapter 1.1.2 --- Photochemistry --- p.3 === Chapter 1.1.3 --- Principal stages of PDT --- p.5 === Chapter 1.1.4 --- Light sources of PDT --- p.6 === Chapter 1.2 --- Anti-tumor effect of PDT --- p.8 === Chapter 1.2.1 --- Mode of cell death --- p.8 === Chapter 1.2.2 --- PDT-induced anti-tumor immunity --- p.9 === Chapter 1.3 --- Clinical applications of PDT --- p.11 === Chapter 1.3.1 --- Photofrin® --- p.11 === Chapter 1.3.2 --- Clinical applications of PDT --- p.13 === Chapter 1.3.3 --- Challenges of PDT for clinical applications --- p.15 === Chapter 1.4 --- The development of new photosensitizers --- p.16 === Chapter 1.4.1 --- Targeted PDT --- p.16 === Chapter 1.4.2 --- Phthalocyanine --- p.18 === Chapter 1.5 --- Objective of my study --- p.21 === Chapter Chapter 2 --- Materials and Methods --- p.23 === Chapter 2.1 --- Synthesis of glucosylated silicon(IV) phthalocyanine (SiPcGlu) --- p.24 === Chapter 2.2 --- In vitro studies --- p.24 === Chapter 2.2.1 --- Cell line and culture conditions --- p.24 === Chapter 2.2.2 --- Photodynamic treatment --- p.25 === Chapter 2.2.3 --- Cell viability assay --- p.27 === Chapter 2.2.4 --- Light dose effect on the photocytotoxicity of SiPcGlu-PDT --- p.27 === Chapter 2.2.5 --- Determination of reactive oxygen species (ROS) production by SiPcGlu-PDT --- p.29 === Chapter 2.2.6 --- Effect of antioxidants on the photocytotoxicity of SiPcGlu-PDT --- p.29 === Chapter 2.2.7 --- Determination of ROS production after SiPcGlu-PDT --- p.30 === Chapter 2.2.8 --- Glucose competitive assay --- p.30 === Chapter 2.2.9 --- Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay --- p.30 === Chapter 2.2.10 --- DNA fragmentation analysis by gel electrophoresis --- p.31 === Chapter 2.2.11 --- Annexin-V & propidium iodide staining assay --- p.32 === Chapter 2.2.12 --- Subcellular localization studies --- p.33 === Chapter 2.2.13 --- Detection of mitochondrial superoxide production --- p.34 === Chapter 2.2.14 --- Assessment of mitochondrial membrane potential --- p.34 === Chapter 2.2.15 --- Caspase-3 activity assay --- p.35 === Chapter 2.2.16 --- "Western blot analyses for cytochrome c, caspase-3, PARP and glucose-regulated protein 78 (GRP78)" --- p.36 === Chapter 2.2.17 --- Ca2+ release from endoplasmic reticulum (ER) --- p.37 === Chapter 2.3 --- In vivo studies --- p.37 === Chapter 2.3.1 --- HT29 tumor-bearing nude mice model --- p.37 === Chapter 2.3.2 --- In vivo photodynamic treatment --- p.39 === Chapter 2.3.3 --- Biodistribution of SiPcGlu --- p.39 === Chapter 2.3.4 --- Assay for plasma enzyme activities --- p.40 === Chapter 2.4 --- Statistical analysis --- p.41 === Chapter Chapter 3 --- Results --- p.42 === Chapter 3.1 --- In vitro studies --- p.43 === Chapter 3.1.1 --- SiPcGlu-PDT induced cytotoxicity on HT29 cells --- p.43 === Chapter 3.1.2 --- Light dose effect on cytotoxicity by SiPcGlu-PDT --- p.46 === Chapter 3.1.3 --- SiPcGlu-PDT induced ROS production --- p.48 === Chapter 3.1.4 --- SiPcGlu-PDT induced cell death through Type I and II photoreactions --- p.48 === Chapter 3.1.5 --- ROS production after SiPcGlu-PDT --- p.51 === Chapter 3.1.6 --- Glucose competitive Assay --- p.55 === Chapter 3.1.7 --- SiPcGlu-PDT induced apoptosis in HT29 cells --- p.57 === Chapter 3.1.8 --- Subcellular localization of SiPcGlu --- p.61 === Chapter 3.1.9 --- SiPcGlu-PDT induced mitochondrial changes --- p.66 === Chapter 3.1.10 --- SiPcGlu-PDT induced caspase activation --- p.68 === Chapter 3.1.11 --- SiPcGlu-PDT increased expression of ER chaperone GRP78 --- p.72 === Chapter 3.1.12 --- SiPcGlu-PDT induced release of Ca2+ from ER --- p.72 === Chapter 3.2 --- In vivo studies --- p.75 === Chapter 3.2.1 --- In vivo photodynamic activities --- p.75 === Chapter 3.2.2 --- Tissue distribution of SiPcGlu --- p.77 === Chapter 3.2.3 --- Analysis of intrinsic toxicity --- p.77 === Chapter Chapter 4 --- Discussion --- p.80 === Chapter 4.1 --- Physical Properties of SiPcGlu --- p.81 === Chapter 4.2 --- In vitro studies --- p.82 === Chapter 4.2.1 --- SiPcGlu-PDT exhibits a high potency in killing HT29 cells --- p.82 === Chapter 4.2.2 --- ROS production is responsible for the cytotoxic effect of SiPcGlu-PDT --- p.83 === Chapter 4.2.3 --- SiPcGlu-PDT induced apoptosis in HT29 cells --- p.85 === Chapter 4.2.4 --- SiPcGlu is localized in various membranous organelles --- p.87 === Chapter 4.2.5 --- SiPcGlu-PDT induced mitochondria-mediated apoptosis --- p.89 === Chapter 4.2.6 --- SiPcGlu-PDT induced ER stress --- p.93 === Chapter 4.3 --- In vivo studies --- p.96 === Chapter 4.3.1 --- SiPcGlu failed to target to tumor tissues --- p.96 === Chapter 4.3.2 --- SiPcGlu-PDT induced retardation in tumor growth --- p.99 === Chapter 4.3.3 --- SiPcGlu is a safe photosensitizer for PDT --- p.101 === Chapter Chapter 5 --- Conclusion and Future Perspectives --- p.103 === Chapter 5.1 --- Conclusion --- p.104 === Chapter 5.2 --- Future Perspectives --- p.106 === Chapter 5.2.1 --- In vitro studies --- p.106 === Chapter 5.2.1.1 --- Lysosomal pathway to cell death --- p.106 === Chapter 5.2.2 --- In vivo studies --- p.107 === Chapter 5.2.2.1 --- Pharmacokinetic studies --- p.107 === Chapter 5.2.2.2 --- Eradication of HT29 tumor by repeated dose of SiPcGlu --- p.108 === Chapter 5.2.2.3 --- SiPcGlu-PDT-induced anti-tumor immunity --- p.108 === Chapter 5.2.2.4 --- Enhancement of tumor selectivity by conjugating with biomolecules --- p.109 === References --- p.110