BODIPY dyes for mitochondria-targeted cell imaging and photodynamic therapy of cancer cells
- Issued Date
- 2022
- Abstract
- 미토콘드리아를 표적으로 하는 유망한 광역학 물질의 개발을 위해 BODIPY에서 유도된 일련의 나노 물질이 합성되었다. 크기가 작은 분자는 표적 영역에 대한 가용성의 이점을 가지고 있다. BODIPY인 AmH2, AmBr2 및 AmI2는 음전하를 띤 미토콘드리아에 편재화를 할 수 있는 양이온성 트라이메틸암모늄 기를 중간 위치에 가지고 있다. 이들 구조에 포함된 할로젠(브로민 및 아이오딘)의 중원자 효과는 향상된 시스템 간 교차(ISC)를 일으켜서 이들을 광역학적 물질로 적합하게 해준다. 그러나, 이들은 짧은 흡수 파장을 가지고 있어서 근적외선(NIR) 활성화를 방해한다. 근적외선은 조직 깊숙이 침투하여 자가형광을 극복할 수 있어서 바람직하다. PyBHI, PyBMI 및 PyBBrI는 흡수 스펙트럼을 NIR 영역으로 이동시키는 확장된 π-콘쥬게이션을 갖는 형광단과 친수성을 위한 PEG 코일을 가지고 있다. 브로민 원자는 염료의 형광 이미징 능력을 감소시키지 않으면서 감광 능력을 제공한다. 마지막으로, 염료의 효율적인 전달과 표적 외 효과를 줄이기 위하여 나노젤로 중합된 BN-H2 및 BN-Br2는 형광단/광역학제를 통합하여 가지고 있다. 나노젤은 열역학적 N-아이소프로필아마이드(N-isopropylacrylamide, NIPAM), 2-하이드록시에틸 메타크릴레이트(2-hydroxyethyl methacrylate, HEMA) 및 이중 색 형광 이미징 기능을 위한 두 개의 형광단인 나이트로벤조옥사다이아졸(nitrobenzoxadiazole, NBD)과 BODIPY로 구성되어 있다.|A series of BODIPY-derived nanomaterials are synthesized for the development of promising mitochondria-targeting photodynamic agents. Small molecules possess the advantage of size and availability to target areas. BODIPYs AmH2, AmBr2 and AmI2 have cationic trimethylammonium groups on the meso-position that allows localization to the negatively charged mitochondria. The halogens (bromine and iodine) featured in the structure makes them ideal as photodynamic agents brought about by the enhanced intersystem crossing (ISC) due to heavy-atom effect. However, they have short absorption wavelength which deters near-infrared (NIR) -activation. NIR light is preferable because it penetrates deeper into tissues and overcomes autofluorescence. PyBHI, PyBMI and PyBBrI are fluorophores with extended π-conjugation resulting to shifts in absorption spectra to the NIR region and PEG coils for hydrophilicity. The presence of bromine atoms imparts photosensitizing ability without diminishing the fluorescence imaging ability of the dyes. Lastly, the polymerized BN-H2 and BN-Br2 incorporate the fluorophore/photodynamic agent in a nanogel for an efficient delivery and lessened off-target effects of the dyes. The nanogel consists of N-isopropylacrylamide (NIPAM), 2-hydroxyethyl methacrylate(HEMA), and two fluorophores nitrobenzoxadiazole (NBD) and BODIPY for a dual-chromatic fluorescence imaging ability.
- Alternative Title
- 암세포의 미토콘드리아 표적 세포 영상화 및 광역학 치료를 위한 BODIPY 염료
- Alternative Author(s)
- BADON ISABEL WEN
- Affiliation
- 조선대학교 일반대학원
- Department
- 일반대학원 화학과
- Advisor
- 김호중
- Awarded Date
- 2022-08
- Table Of Contents
- Table of Contents i
LIST OF PUBLICATIONS v
LIST OF TABLES vi
LIST OF FIGURES vii
LIST OF ABBREVIATIONS x
ABSTRACT xi
CHAPTER 1: Mitochondria-targeting BODIPY dyes 1
1.1. Cancer and Mitochondria 1
1.2. Photodynamic therapy for cancer treatment 2
1.3. Synthesis of BODIPY 4
1.4. BODIPY-derived materials for synergistic cell imaging and photodynamic therapy applications 5
CHAPTER 2: Cationic BODIPYs for mitochondria-targeted cell imaging and photodynamic therapy 8
2.1. Introduction 8
2.2. Experimental Section 9
2.2.1. Materials 9
2.2.2. Synthesis of BODIPY H1 9
2.2.3. Halogenation reaction 10
2.2.4. Methylation reaction 10
2.2.5. Methods 11
2.2.6. Cells and cell culture 11
2.2.7. Cell proliferation assay 12
2.2.8. Photodynamic activity 12
2.2.9. Confocal laser scanning microscopy 12
2.2.10. Statistical Analysis 13
2.3. Results and Discussion 13
2.3.1. Photophysical Properties 13
2.3.2. Cell Proliferation 15
2.3.3. Mitochondria-targeted cell imaging 17
CHAPTER 3: Near-infrared BODIPY dyes for synergistic mitochondria-targeted cell imaging and photodynamic therapy 27
3.1. Introduction 27
3.2. Experimental Section 27
3.2.1. Materials 27
3.2.2. Synthesis of BODIPY dye 1a 28
3.2.3. Mono- and dibromination of BODIPY 1a 29
3.2.4. Synthesis of triethylene glycol tosylate 29
3.2.5. Synthesis of diPEGylated benzaldehyde (PEG-CHO) 30
3.2.6. Knoevenagel Condensation Reaction 30
3.2.7. Methylation of BODIPY compounds 31
3.2.8. Methods 33
3.2.9. Singlet oxygen quantum yield measurements 33
3.2.10. Quantum chemical calculations 34
3.2.11 Cells and cell culture 34
3.2.12. Cell proliferation assay 34
3.2.13. Photodynamic activity 35
3.2.14. Confocal laser scanning microscopy 35
3.2.15. Statistical Analysis 35
3.3. Results and Discussion 35
3.3.1. Photophysical Properties 36
3.3.2. Cell proliferation and phototoxicity 41
3.3.3. Mitochondria-targeted cell imaging 43
CHAPTER 4: BODIPY functionalized NIPAM nanogels for dual-chromatic cell imaging and photodynamic therapy 57
4.1. Introduction 57
4.2. Experimental Section 58
4.2.1 Materials 58
4.2.2. Synthesis of Bromobutyl-BODIPY 1 59
4.2.3. Methacrylation of Bromobutyl-BODIPY 1 59
4.2.4. Dibromination reaction of BODIPY 2 60
4.2.5. Knoevenagel condensation reaction (Monostyryl) of BODIPY 3 60
4.2.6. Methylation reactions of 4 and 5 61
4.2.7. Synthesis of Nitrobenzoxadiazole-methacrylate (NBD-MA) 61
4.2.8. Synthesis of BN-H2 and BN-Br2 nanogels 62
4.2.9. Methods 63
4.2.10. Cells and cell culture 64
4.2.11. Cell proliferation assay 64
4.2.12. Photodynamic activity 64
4.2.13. Confocal laser scanning microscopy 65
4.2.14. Annexin V/PI assay 65
4.2.15 Statistical Analysis 65
4.3. Results and Discussion 66
4.3.1. Photophysical Properties 66
4.3.2. Flow Cytometry 68
4.3.3. Cell Proliferation 70
4.3.4. Dual-color fluorescence cell imaging 70
4.3.5. Mitochondria-targeted cell imaging 72
Conclusions 77
References 78
Acknowledgments 85
- Degree
- Doctor
- Publisher
- 조선대학교 대학원
- Citation
- 바돈 이사벨 웬. (2022). BODIPY dyes for mitochondria-targeted cell imaging and photodynamic therapy of cancer cells.
- Type
- Dissertation
- URI
- https://oak.chosun.ac.kr/handle/2020.oak/17396
http://chosun.dcollection.net/common/orgView/200000635941
- Appears in Collections:
- General Graduate School > 4. Theses(Ph.D)
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