Synthesis and Photophysical Investigation of Tumor-Targeted BODIPY Derivatives for Photodynamic Therapy
- Issued Date
- 2021
- Abstract
- We reported the synthesis of three lactose-functionalized 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based dyes capable of targeting cancer cells and investigated their photodynamic therapeutic property on three distinct malignant cell lines (breast cancer MCF-7 cell lines, cervical cancer HeLa, and human hepatoma Huh7). The halogenation of BODIPY dyes has resulted to a decreased fluorescence quantum yield and effectively facilitated the high production of singlet oxygen species. The synthesized BODIPY derivatives demonstarted low cytotoxicities in the dark and high photodynamic therapeutic capabilities against the treated cancer cell lines after LED irradiation. Furthermore, the modification with the lactose and triphenylphosphine groups resulted to an increased cellular uptake of the BODIPY dyes. In summary, the results presented herein signify the promising potentials of BODIPY dyes as photodynamic therapeutic agents for cancer treatment.|종양 표적화 능력을 가진 세 개의 수용성 lactose이 결합된 BODIPY(4,4-difluoro-4-bora-3a, 4a-diaza-s-indacene)기반 광감작제 의 합성이 보고되었습니다. 그것들은 세 개의 서로 다른 암세포주(인간 Huh7, 자궁 경부암 HeLa 및 유방암 MCF-7 세포주)에 대한 광역학치료 연구를 포함합니다. 할로겐화된 BODIPY 염료들은 할로겐화되지 않은 것들에 비하여 형광 양자수율이 감소했고, 단일항 산소종의 효율적인 생성을 가능하게 했습니다. 합성된 염료들은 치료 암세포주에 대해 530nm에서 조사 후 어둠에서 낮은 세포독성과 높은 광역학 치료능력을 나타냈습니다. 게다가, lactose의 결합은 BODIPY 염료의 세포 흡수를 향상시켰습니다. 전체적으로 이 결과들은 암 치료에 대한 광역학 치료제의 개발에 대해 전망있는 통찰력을 제공하였습니다.
- Alternative Title
- 광역학치료를 위한 암-표적지향 BODIPY 유도체의 합성과 분광학적 분석
- Alternative Author(s)
- TEMMY VALES
- Department
- 일반대학원 화학과
- Advisor
- 김호중
- Awarded Date
- 2021-02
- Table Of Contents
- TABLE OF CONTENTS i
LIST OF SCHEMES ii
LIST OF FIGURES iii
LIST OF TABLES vi
LIST OF PUBLICATIONS vii
ACKNOWLEDGEMENT ix
ABSTRACT x
PART 1 Introduction
1.1. General features and synthesis of the paent BODIPY core 1
1.2. Functionalization via the meso substituent 3
1.3. Halogenated BODIPY dyes. 5
1.4. Research Outlook. 7
1.5. References. 7
PART 2 Synthesis and Photophysical Properties of Tumor-Targeted Water-Soluble BODIPY Photosensitizers for Photodynamic Therapy
2.1. Introduction. 10
2.2. Materials and Methods 13
2.2.1. Materials 13
2.2.2. Synthesis of Lactose-Modified Water Soluble BODIPY Derivatives. 13
2.2.2.1. Synthesis of the BODIPY Core. 13
2.2.2.2. Synthesis of Dye 1 14
2.2.2.3. Synthesis of BODIPY Dyes 2a and 2b 15
2.2.2.4. General Procedure for the Preparation of Water-Soluble Dyes BLa, BILa, and BDILa. 15
2.2.3. Measurement of Photophysical Properties. 17
2.2.4. Fluorescence Quantum Yield Measurements. 18
2.2.5. Singlet Oxygen Quantum Yield 18
2.2.6. Cells and Cultures 19
2.2.7. Photodynamic Anticancer Activity Assessment. 19
2.2.8. Cell Proliferation Assay. 20
2.2.9. Cellular Uptake by Flow Cytometry 20
2.2.10. Theoretical Calculations. 21
2.2.11. Statistical Analysis. 21
2.3. Results and Discussion 22
2.3.1. Design and Synthesis of Water-Soluble BODIPY Dyes 22
2.3.2. Photophysical and Theoretical Characterizations of Water-Soluble BODIPY Dyes 24
2.3.3. Singlet Oxygen Generation of Water-Soluble BODIPY Dyes 28
2.3.4. Assessment of Cytotoxicity of the Water-Soluble BODIPY Dyes. 30
2.3.5. Cellular Uptake by Flow Cytometry 33
2.3.6. Photodynamic Anticancer Activity of the Water-Soluble BODIPY Dyes. 37
2.4. Conclusions. 40
2.5. References. 47
PART 3 Facile Synthesis of Mitochondria-Targeting Triphenyphosphine-Modified BODIPY Derivatives for Photodynamic Therapy
3.1. Introduction. 52
3.2. Materials and Methods 55
3.2.1. Chemicals and equipment 55
3.2.2. Synthesis of TPP-functionalized BODIPY Derivatives. 55
3.2.2.1. Synthesis of Dye 1 55
3.2.2.2. Synthesis of BODIPY Dyes 2a and 2b 56
3.2.2.3. General Procedure for the Preparation of TPP-functionalized BODIPY Derivatives 57
3.2.3. Measurement of photophysical properties 59
3.2.4. Fluorescence Quantum Yield Measurements. 59
3.2.5. Singlet Oxygen Quantum Yield 60
3.2.6. Cells and Cultures 60
3.2.7. Cell Proliferation Assay. 61
3.2.8. Photodynamic Anticancer Activity Assessment. 61
3.2.9. Morphological Assessment of Active Mitochondria by Fluorescent Imaging 62
3.2.10. Statistical Analysis. 62
3.3. Results and Discussion 63
3.3.1. Design and Synthesis of TPP-functionalized BODIPY Derivatives. 63
3.3.2. Singlet Oxygen Generation of TPP-functionalized BODIPY Derivatives. 64
3.3.3. Photodynamic Anticancer Activity of TPP-functionalized BODIPY Derivatives 66
3.3.4. Morphological Assessment of Active Mitochondria by Fluorescent Imaging 68
3.4. Conclusions. 70
3.5. References. 75
- Degree
- Doctor
- Publisher
- 조선대학교 대학원
- Citation
- 테미 발레스. (2021). Synthesis and Photophysical Investigation of Tumor-Targeted BODIPY Derivatives for Photodynamic Therapy.
- Type
- Dissertation
- URI
- https://oak.chosun.ac.kr/handle/2020.oak/16783
http://chosun.dcollection.net/common/orgView/200000372649
- Appears in Collections:
- General Graduate School > 4. Theses(Ph.D)
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