Preparation of Near-Infrared-Absorbing Nanoparticles for Cancer Bioimaging and Photothermal Treatment
- Abstract
- Cancer is among the leading causes of death worldwide. Cancer theragnosis agents with both cancer diagnosis and therapy abilities would be the next generation of cancer treatment. Recently, nanomaterials with strong absorption in near-infrared (NIR) region have been explored as promising cancer theragnosis agents for bio-imaging and photothermal therapy. In this dissertation, we reported the preparation of several advanced nanomaterials systems with biocompatible, strong NIR-absorbing properties. We offered the novel green method to synthesis NIR-absorbing agents to alter the costly and toxic traditional methods. The in vitro and in vivo photothermal anticancer activity results of the designed nanoparticles evidenced their promising potential in cancer treatment. The nanoparticles also gave the good amplitude of photoacoustic signals, which facilitates the imaging of tumor tissues using a non-invasive photoacoustic tomography system. Thus, our works highlight the great potential of using NIR-absorbing agents as theranostic nanoplatforms for cancer imaging-guided therapy.
- Issued Date
- 2019
- Awarded Date
- 2019. 2
- Type
- Dissertation
- Publisher
- 부경대학교
- Affiliation
- 부경대학교 대학원
- Department
- 대학원 의생명기계전기융합공학협동과정
- Advisor
- 오정환
- Table Of Contents
- PART 1: INTRODUCTION 1
1. Motivation 1
2. Near-infrared window and near-infrared absorbing agents 1
3. Cancer photothermal therapy 6
4. Bioimaging on detection of cancer 9
5. Green synthesis for near-infrared absorbing nanoparticles 10
6. The techniques used to characterize the nanoparticles 11
6.1. Transmission electron microscopy 11
6.2. X-ray diffraction 12
6.3. UV-Vis spectroscopy 13
6.4. Fourier-transform infrared spectroscopy 14
6.5. Dynamic light scattering 15
6.7. Zeta potential 16
7. The technique used to read the result of photothermal effect on cells 17
7.1. MTT 17
7.2. Trypan blue staining 17
7.3. Hoechst 33342 and propidium iodide double staining 17
7.4. Acridine orange and propidium iodide double staining 18
8. References 18
PART 2: NEAR-INFRARED-ABSORBING NANOPARTICLES FOR BIOIMAGING AND PHOTO-BASED THERAPIES ON CANCER TREATMENT 20
Chapter 1: Synthesis and In vitro Performance of Polypyrrole coated Iron–Platinum Nanoparticles for Photothermal Therapy and Photoacoustic Imaging 21
1. Introduction 21
2. Materials and Methods 22
2.1. Materials 22
2.2. Synthesis of FePt@PPy NPs 23
2.3. Characterization 25
2.4. Photothermal test 26
2.5. Photostability test 26
2.6. Long-term storage test 26
2.7. Cytotoxicity assay of FePt@PPy NPs 26
2.8. Cellular uptake 27
2.9. In vitro photothermal therapy 27
2.10. Animal experiment 28
2.11. In vitro photoacoustic imaging 29
3. Results and Discussion 29
3.1. Synthesis and characterization of FePt@PPy NPs 29
3.2. Photothermal performance of FePt@PPy NPs 32
3.3. Photothermal stability tests of FePt@PPy NPs 34
3.4. Long-term storage test 35
3.5. In vitro cell cytotoxicity assay 36
3.6. Cellular uptake 37
3.7. In vitro photothermal therapy 37
3.8. In vivo laser heating experiment 39
3.9. In vitro photoacoustic imaging 41
4. Conclusion 42
5. References 44
Chapter 2: Photoacoustic Imaging-Guided Photothermal Therapy with Tumor-Targeting HA-FeOOH@PPy Nanorods 46
1. Introduction 46
2. Materials and Methods 48
2.1. Chemicals 48
2.3. Synthesis of HA-FeOOH@PPy NRs 49
2.4. Characterization of HA-FeOOH@PPy NRs 49
2.5. Heating effect evaluation 50
2.6. Cell line and cell culture condition 51
2.7. Cell uptake and in vitro cell cytotoxicity assay 51
2.8. In vitro photothermal therapy 51
2.9. Animal and tumor model 52
2.10. In vitro and in vivo photoacoustic therapy 52
2.11. In vivo photothermal therapy 53
2.12. Histological analysis 54
3. Results 54
3.1. Synthesis and characterization of HA-FeOOH@PPy NRs 54
3.2. Photothermal effects of HA-FeOOH@PPy NRs 57
3.3. Cell uptake and in vitro cell cytotoxicity assay 60
3.4. Photothermal ablation of cancer cells in vitro 60
3.5. In vitro and in vivo photoacoustic imaging 62
3.6. In vivo photothermal therapy 64
4. Discussion 66
5. References 76
Chapter 3: Polypyrrole-Methylene Blue Nanoparticles as a Single Multifunctional Nanoplatform for Near-Infrared Photo-induced Therapy and Photoacoustic Imaging 80
1. Introduction 80
2. Materials and Methods 82
2.1. Materials 82
2.2. Synthesis of polypyrrole-methylene blue nanoparticles 83
2.3. Characterization 84
2.4. Singlet oxygen generation test: DPBF assay 85
2.5. Photothermal test 85
2.6. Long-term storage stability 85
2.7. Photostability tests 86
2.8. In vitro cell cytotoxicity assay 86
2.9. In vitro combined photothermal and photodynamic therapy 87
2.10. Intracellular ROS detection: DCFH-DA staining 88
2.11. In vitro photoacoustic imaging 88
3. Results and Discussion 89
3.1. Synthesis and characterization of polypyrrole-methylene blue nanoparticles 89
3.2. Photothermal performance of polypyrrole-methylene blue nanoparticles 93
3.3. Photodynamic property of polypyrrole-methylene blue nanoparticles 94
3.4. Long-term storage stability tests of polypyrrole-methylene blue nanoparticles 95
3.5. Photostability tests of polypyrrole-methylene blue nanoparticles 96
3.6. In vitro cell cytotoxicity assay 97
3.7. In vitro combined photothermal and photodynamic therapy 97
3.8. Intracellular ROS detection 100
3.9. In vitro photoacoustic imaging 101
4. Conclusion 102
5. References 108
PART 3: NOVEL METHODS FOR PREPARATION OF NEAR-INFRARED-ABSORBING NANOPARTICLES 111
Chapter 1: Coating Chitosan Thin Shells: A Facile Technique to Improve Dispersion Stability of Magnetoliposomes 112
1. Introduction 112
2. Materials and Methods 114
2.1. Materials 114
2.2. Synthesis of Fe3O4 nanoparticles 114
2.3. Synthesis of magnetoliposomes 115
2.4. Synthesis of chitosan-coated magnetoliposomes 116
2.5. Drug loading of chitosan-coated magnetoliposomes 116
3. Results and Discussion 118
3.1. Characterization of Fe3O4 nanoparticles 118
3.2. Characterization of magnetoliposomes and chitosan coated magnetoliposomes 119
3.3. The stability of chitosan coating magnetoliposomes in long-term storage 124
3.4. Drug encapsulation efficiency and drug release profile from chitosan coated magnetoliposomes 125
4. Conclusion 126
5. References 127
Chapter 2: Chitosan as a Stabilizer and Size-control Agent for Synthesis of Porous Flower-shaped Palladium Nanoparticles and Their Applications on Photo-based Therapies 130
1. Introduction 130
2. Materials and Methods 132
2.1. Materials 132
2.2. One-spot synthesis of CFP nanoparticles 132
2.3. Quantification of the reducing rate of PdII following reaction time 133
2.4. Characterization 133
2.5. Heating effect evaluation 134
2.6. Cell line and cell culture condition 134
2.7. Cell intracellular uptake 135
2.8. Cell cytotoxicity assay 135
2.9. In vitro photothermal therapy 136
2.10. In vitro photoacoustic imaging 136
3. Results and Discussion 137
3.1. Chitosan as a stabilizer for the synthesis of CFP nanoparticles 137
3.2. Formation process of CFP nanoparticles 137
3.3. Chitosan as a size-control agent for the synthesis of CFP nanoparticles 140
3.4. Characterization studies of CFP nanoparticles 141
3.5. Photothermal performance of CFP nanoparticles 145
3.6. Photoacoustic performance of CFP nanoparticles 151
4. Discussion 152
5. References 160
Chapter 3: Chitosan-mediated Facile Green Synthesis of Size-controllable Gold Nanostars for Effective Photothermal Therapy and Photoacoustic Imaging 162
1. Introduction 162
2. Materials and Methods 163
2.1. Materials 163
2.2. One-spot synthesis of AuNS 163
2.3. Characterization 163
2.4. Heating effect evaluation 164
2.5. Cell line and cell culture condition 164
2.6. Cell uptake study 165
2.7. Biocompatibility study 165
2.8. In vitro photothermal therapy 165
2.9. In vitro photoacoustic imaging 166
3. Results and Discussion 166
3.1. The role of pH 166
3.2. Proposed growth model of AuNS nanoparticles 168
3.3. Chitosan as a controllable nanoparticle size agent for the synthesis of AuNS 170
3.4. Characterization studies of AuNS 172
3.5. Photothermal performance of AuNS 175
3.6. Photoacoustic performance of AuNS 179
4. Conclusion 180
5. References 183
PART 4: CONCLUSION 185
1. Findings 185
2. Further Directions 188
2.1. Green synthesis of NIR-absorbing nanoparticles 188
2.2. Hydrogel/membrane containing nanoparticles for treatment of an infected wound 189
PUBLICATIONS 191
- Degree
- Doctor
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