Design, synthesis, and characterization of advanced fluorescent probes and multi-functional photo-therapeutics

다국어 초록 (Multilingual Abstract)

Harnessing the cutting-edge photonics and optical techniques have made impacts on modern diagnostics and therapeutics for assessing and treating disease in biomedical fields. With unprecedented interests in advanced fluorescent probes and multi-functional photo-therapeutics, numerous studies are devoted to developing effective diagnostics and therapeutics for various diseases. Despite the tremendous efforts, many obstacles are yet to be overcome. As part of it, studies have been conducted to rectify previous limitations while improving efficiency, enhancing existing remedies and sensors, or even developing new medical agents. This study focused on the design, synthesis, and characterization of advanced fluorescent probes and multi-functional photo-therapeutics.
In part Ⅰ (chapters 2 and 3), advanced fluorescent probes were developed by utilizing the concept of twisted-intramolecular charge transfer (TICT) and photo-induced electron transfer (PeT), respectively. The introduction of the TICT-based de-excitation pathway significantly increased fluorescence in the presence of amyloid-β (Aβ) fibrils while maintaining an excellent two-photon cross-section, leading to high-contrast ex vivo and in vivo two-photon microscopy (TPM) imaging. Furthermore, a novel PeT-based methylglyoxal-sensitive fluorophore selectively visualizes cellular senescence, which had been limited in diagnosis due to the lack of proper probes and effective biomarkers.
In part Ⅱ (chapters 4 and 5), attempts to overcome the drawbacks of traditional photo-therapy were investigated via multi-functional photo-therapeutics. A cancerous mitochondria-targeted photo-therapeutic agent for dual-mode imaging (photoacoustic/fluorescence) and photo-therapies (photodynamic /photothermal therapy) was invented. Modified photothermal agent not only induces shifted photon pathways for combined therapies and dual-mode imaging but also enables cancer selectivity. In addition, unprecedented protonation-induced porous organic photosensitizer was established as an oxygen nanocarrier to enhance the efficacy of photodynamic therapy. Interestingly, the polymeric photosensitizer is a type Ⅰ photosensitizer as well as type Ⅱ, which has rectified the less effective photo-therapeutic efficacy due to lack of oxygen.
It is believed that the development of advanced fluorescent probes and multi-functional photo-therapeutics may help improve some limitations of traditional diagnostics and therapeutics. Therefore, the chemical concepts presented in this thesis have tremendous potentials and implications for application in biomedical fields.

목차 (Table of Contents)

• ABSTRACT ⅰ
• CONTENTS ⅲ
• LIST OF SCHEMES ⅵ
• LIST OF FIGURES ⅷ
• LIST OF TABLES ⅹⅹⅹ
• CHAPTER Ⅰ. General Introduction 1
• 1.1. Advanced organic fluorescent probes for disease diagnosis 2
• 1.1.1. Fundamental principles and mechanisms of fluorescence 5
• 1.1.2. Intramolecular charge transfer (ICT) 7
• 1.1.3. Twisted-intramolecular charge transfer (TICT) 9
• 1.1.4. Photo-induced electron transfer (PeT) 12
• 1.1.5. Two-photon excitation microscopy (TPM) and its advantages 14
• 1.2. General background information of Alzheimer's disease (AD) 17
• 1.2.1. Senile plaques/amyloid-β (Aβ) 21
• 1.3. General background information of senescence 23
• 1.4. Multi-functional photo-therapeutics for remedy 30
• 1.4.1. Fundamental principles and mechanisms of photo-therapeutics 34
• 1.4.2. Photothermal therapy (PTT) 36
• 1.4.3. Photodynamic therapy (PDT) 38
• 1.5. Porous organic materials and their applications for cancer therapy 39
• 1.6. References 43
• CHAPTER Ⅱ. Harnessing Intramolecular Rotation to Enhance Two-photon Imaging of Aβ Plaques through Minimizing Background Fluorescence 55
• 2.1. Introduction 56
• 2.2. Results and discussion 58
• 2.3. Calculation details and discussion 92
• 2.4. Conclusion 100
• 2.5. Experimental section 101
• 2.6. References 113
• CHAPTER Ⅲ. Methylglyoxal-activated OFF-ON Fluorophore: The Advance in Developing Senescence Selective Fluorescent Probe 120
• 3.1. Introduction 121
• 3.2. Results and discussion 124
• 3.3. Calculation details and discussion 150
• 3.4. Conclusion 152
• 3.5. Experimental section 153
• 3.6. References 164
• CHAPTER Ⅳ. Mitochondria-targeted Nanotheranostic: Harnessing Single Laser Activated Dual Photo-therapeutic Processing for Hypoxic Tumor Treatment 171
• 4.1. Introduction 172
• 4.2. Results and discussion 177
• 4.3. Conclusion 219
• 4.4. Experimental section 220
• 4.5. References 243
• CHAPTER Ⅴ. Protonation-induced Porous Organic Photosensitizer: An Oxygen Nanocarrier for Enhanced Photodynamic Therapy 252
• 5.1. Introduction 253
• 5.2. Results and discussion 256
• 5.3. Conclusion 282
• 5.4. Experimental section 283
• 5.5. References 288
• CHAPTER Ⅵ. Summary 292
• CHAPTER Ⅶ. Acknowledgments in Korean 295