Lau J.T.F. Towards dual and targeted cancer therapy with novel phthalocyanine-based photosensitizers: doctoral thesis accepted by the Chin. Univ. of Hong Kong, Shatin, People's Republic of China. - Cham [et al.]: Springer , 2013. - xxii, 180 p.: ill. - (Springer theses: recognizing outstanding Ph.D. research). - Incl. bibl. ref. - ISBN 978-3-319-00707-6; ISSN 2190-5053 Шифр: (И/Р56-L37) 02  Место хранения:   02 | Отделение ГПНТБ СО РАН | Новосибирск

Оглавление / Contents

1 Introduction ............................................... 1 1.1 Introduction ............................................... 1 1.1.1 History of Photodynamic Therapy ..................... 1 1.1.2 Basic Principles of Photodynamic Therapy ............ 2 1.2 Photosensitizers of Photodynamic Therapy ................... 6 1.2.1 Characteristics of Ideal Photosensitizers ........... 7 1.2.2 First-Generation Photosensitizers ................... 8 1.2.3 Second-Generation Photosensitizers ................. 10 1.2.4 Phthalocyanine-Based Photosensitizers .............. 13 1.3 Toward Targeted Photodynamic Therapy ...................... 17 1.3.1 Site-Specific Delivery of Photosensitizers ......... 17 1.3.2 Activatable Photosensitizers ....................... 20 1.4 Dual Chemo- and Photodynamic Therapy ...................... 25 1.4.1 Covalent Conjugation ............................... 25 1.4.2 Co-encapsulation in Polymeric Micelles ............. 27 1.4.3 Sequential Administration .......................... 28 1.5 Objectives of this Study .................................. 30 References ................................................ 30 2 A Zinc(II) Phthalocyanine Conjugated with an Oxaliplatin Derivative for Dual Chemo- and Photodynamic Therapy ....... 35 2.1 Introduction .............................................. 35 2.2 Results and Discussion .................................... 36 2.2.1 Molecular Design, Synthesis, and Characterization .. 36 2.2.2 Electronic Absorption and Photophysical Properties ......................................... 38 2.2.3 In Vitro Photodynamic Activities ................... 40 2.3 Summary ................................................... 47 References ................................................ 47 3 Zinc(II) Phthalocyanine-Polyamine Conjugates as Efficient Photosensitizers for Photodynamic Therapy ................. 49 3.1 Introduction .............................................. 49 3.2 Results and Discussion .................................... 50 3.2.1 Preparation and Characterization ................... 50 3.2.2 Electronic Absorption and Photophysical Properties ......................................... 53 3.2.3 In Vitro Photodynamic Activities ................... 56 3.3 Summary ................................................... 64 References ................................................ 64 4 A Redox-Responsive Silicon(IV) Phthalocyanine for Targeted Photodynamic Therapy ............................. 67 4.1 Introduction .............................................. 67 4.2 Results and Discussion .................................... 68 4.2.1 Preparation and Characterization ................... 68 4.2.2 Electronic Absorption and Photophysical Properties ......................................... 70 4.2.3 In Vitro Photodynamic Activities ................... 77 4.3 Summary ................................................... 81 References ................................................ 81 5 A Dual pH- and Redox-Responsive Phthalocyanine-Based Photosensitizer for Targeted Photodynamic Therapy ......... 83 5.1 Introduction .............................................. 83 5.2 Results and Discussion .................................... 84 5.2.1 Molecular Design, Synthesis, and Characterization .. 84 5.2.2 Electronic Absorption and Photophysical Properties ......................................... 87 5.2.3 pH- and Redox-Responsive Properties ................ 92 5.2.4 In Vitro Photodynamic Activities ................... 99 5.3 Summary .................................................. 103 References ............................................... 103 6 Conclusion and Future Outlook ............................ 105 7 Experimental Section ..................................... 107 7.1 General .................................................. 107 7.1.1 Materials and Methods ............................. 107 7.1.2 Photophysical Measurements ........................ 108 7.1.3 Cell Lines and Culture Conditions ................. 109 7.1.4 Photocytotoxicity Assay ........................... 109 7.1.5 ROS Measurements .................................. 110 7.1.6 Intracellular Fluorescence Studies ................ 110 7.1.7 Cellular Uptake Determined by an Extraction Method ............................................ 110 7.1.8 Subcellular Localization Studies .................. 111 7.1.9 Flow Cytometric Studies ........................... 111 7.2 Experiments Described in Chapter 2 ....................... 112 7.2.1 Synthesis ......................................... 112 7.2.2 Photocytotoxicity Assay ........................... 119 7.2.3 Intracellular Fluorescence Studies ................ 120 7.2.4 Cellular Uptake Determined by an Extraction Method ............................................ 120 7.2.5 Subcellular Localization Studies .................. 120 7.3 Experiments Described in Chapter 3 ....................... 120 7.3.1 Synthesis ......................................... 120 7.3.2 Photocytotoxicity Assay ........................... 131 7.3.3 Effect of Spermidine on the Cellular Uptake ....... 132 7.3.4 Intracellular Fluorescence Studies ................ 132 7.3.5 Subcellular Localization Studies .................. 132 7.4 Experiments Described in Chapter 4 ....................... 133 7.4.1 Synthesis ......................................... 133 7.4.2 Redox-Responsive Fluorescence Emission Studies .... 138 7.4.3 Redox-Responsive Singlet Oxygen Generation Studies ........................................... 139 7.4.4 Photocytotoxicity Assay ........................... 139 7.4.5 Intracellular Fluorescence Studies ................ 139 7.4.6 Subcellular Localization Studies .................. 140 7.5 Experiments Described in Chapter 5 ....................... 140 7.5.1 Synthesis ......................................... 140 7.5.2 pH- and Redox-Responsive Fluorescence Emission Studies ........................................... 145 7.5.3 pH- and Redox-Responsive Singlet Oxygen Generation Studies ................................ 145 7.5.4 Intracellular Fluorescence Studies ................ 146 References ............................................... 146 Appendices .................................................... 147