Development of Multi-modality Polymer-coated Quantum Dots forCancer Imaging Open Access

Wang, Hening (2017)

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Cancer has become a large threat to people's health and lives in the world. It is very important if we can achieve the early diagnosis of cancer, which can significantly reduce cancer mortality and improve the life quality of patients. Nanotechnology is currently widely used in cancer diagnosis and treatment. Nanometer-sized Quantum Dots have intrinsic optical, electronic, and structural properties therefore they have found many applications in the biomedical imaging field. For better applications, we need the QDs to have excellent water-stability, biocompatibility and even targeting ability. Here, we design and develop novel biocompatible Hyaluronic acid polymer coated QDs for CD44+ cancer targeted imaging. The resulted QDs not only have good water solubility, biocompatibility, strong stability, but also achieved CD44 receptor targeted cancer cell imaging. The development of multi-modal imaging equipment requires the design for multi-modality imaging probes. We synthesized DTPA and DOTA chelating agent conjugated hyaluronic acid, which can couple magnetic resonance imaging elements-Gd, and PET isotopes-Cu respectively to make a NIR / MR or NIR / PET dual-modality imaging probes. The multi-modality imaging probe holds the ability for fluorescence imaging, magnetic resonance imaging and PET imaging which can complement the advantages of different imaging modality and help to enhance tumor identification and diagnostic capabilities. We expect our novel method to have broad applications in biomedical imaging research, for the realization of precise diagnosis of tumors, as well as to promote personalized medicine.

Table of Contents






1 Introduction 1

1.1 Background 1

1.2 Thesis goals 6

2 Semiconductor Quantum Dots and biological applications 8

2.1 Semiconductor physics and semiconductor nanocrystals 8

2.1.1 Semiconductor physics and nanocrystals 8

2.1.2 Properties of Quantum Dots 10

2.2 Chemical synthesis and coating methods of Quantum Dots 13

2.2.1 Chemical synthesis of QDs 13

2.2.2 QDs coating methods 14

2.2.3 Bioconjugation of QDs 17

2.3 Biological applications of Quantum Dots 18

2.3.1 Fixed cells and tissue staining 18

2.3.2 live cell imaging 20

2.3.3 In vivo animal imaging 21

2.3.4 Challenges and opportunities 22

3 Biocompatible Hyaluronic Acid-cystamine polymer coated QDs for cancer cell imaging 25

3.1 HA applications and the mechanism for targeting CD44 receptor 25

3.1.1 Hyaluronic Acid 25

3.1.2 CD44 receptor 30

3.1.3 HA-based CD44 targeted imaging using QDs 32

3.2 Materials and Methods 33

3.2.1 Materials 33

3.2.2 Methods 34

3.3 Results and Discussions 38

3.3.1 Results 38

3.3.2 Discussions 47

3.4 Summary 49

4 Multi-modality HA coated-QDs for optical/MRI/PET imaging 51

4.1 Background of Multi-modality imaging probes 51

4.1.1 Background 51

4.1.2 Multi-modality QDs probes 55

4.2 HA-DTPA-Gd QDs for dual-modality optical/MRI imaging 61

4.2.1 Materials and Methods 61

4.2.2 Results and Discussions 68

4.2.3 Summary 80

4.3 HA-DOTA-Cu QDs for dual-modality optical/PET imaging 81

4.3.1 Materials and Methods 81

4.3.2 Results and Disscussions 85

4.3.3 Summary 89

4.4 Summary 89

5 Summary 91


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