Graphene Oxide/Polysaccharide Hybrids for Biomedical Applications
생물의학적 응용을 위한 산화그래핀/다당류고분자 복합재료의 제조 및 특성분석

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dc.contributor.advisor차 국 헌-
dc.description학위논문 (박사)-- 서울대학교 대학원 : 화학생물공학부, 2015. 2. 차국헌.-
dc.description.abstractGraphene and graphene oxide (GO), recently considered as one of the most intriguing 2D carbon-based materials, have attracted considerable interest in various research areas, particularly for biomedical applications. During my Ph.D study, I firstly investigated the chemical synthesis of GO sheets and the methods to control their lateral size. However, graphene is hydrophobic, and GO is nethier stable nor compatible in biological environment. For bioapplications, it is necessary to combine with appropriate biocompatible polymers that will give high colloidal stability and prevent the aggregation of graphene materials in harsh biological milieus.
Polysaccharides have shown huge success in a variety of biomedical applications, such as drug delivery, tissue engineering, and molecular imaging, which could be used for surface coating of graphene materials. A hyaluronic acid-graphene oxide (HA-GO) conjugate system was firstly designed based on small GO nanosheets with the size below 100 nm, to take the advantage of this polysaccharide for both specific target effect and GOs colloidal stability, which was expected to be used as drug carriers with dual-targeting properties for cancer targeted delivery.
Subsequently, I studied the molecular weight (MW) effect of HA coated onto GO sheets on their hydrodynamic size, physicochemical properties and biological behavior. In vitro and in vivo studies showed that among three MWs tested, GO sheets grafted with HA of MW 51K were most stable in biological solutions, and showed the most effective cellular internalization and the longest tumor retention.
Thanks to the combination of advantages of HA and GO, the HA-GO conjugate system was successfully utilized as cancer targeted drug nanocarriers in different bioapplications. For example, a photosensitizer Ce6 was physically loaded on HA-GO conjugates for enhanced photodynamic therapy
dc.description.abstracta miRNA sensing platform composed of dye-labeled PNA and HA-GO conjugates was examined for simple and sensitive monitoring of miRNA in vitro and in vivo.
Finally, GO sheets were studied in the formation of novel macroscale hybrid materials. A novel hydrogel, but mechanically weak, was fabricated by simply mixing HA and GO in high concentrations. To design stronger hydrogels, the interactions between chitosan (Chi) and GO were studied through layer-by-layer (LbL) assembly, which would be helpful for hydrogel design in future. Meanwhile, this LbL-assembled Chi/GO multilayers by the spin-assisted method onto flat surfaces were tested with respect to bacterial and cell adhesion. The inhibition of bacterial growth on (Chi/GO)n films could be applied for the antimicrobial coating. (Chi/GO)n films were also demonstrated cell-friendly, and more detailed cell tests are ongoing for the study of cell culture platform.
In conclusion, this dissertation is focused on smart integration of GO sheets and polysaccharides for novel multifuntional hybrid materials and their diverse applications in biomedical research field.
dc.description.tableofcontentsChapter1 Introduction 1
1.1 Graphene and Its Derivatives 1
1.2 Polysaccharides 7
1.3 References 10

Chapter2 Design of Hyaluronic Acid-Conjugated Graphene Oxide Nanosheets 13
2.1 Introduction 13
2.2 Experimental Section 16
2.3 Results and Discussion 22
2.3.1 Preparation of GO 22
2.3.2 Preparation of HA-GO Conjugates 23
2.3.3 Bio-properties of HA-GO Conjugates 26
2.4 Conclusion 35
2.5 References 36

Chapter3 Molecular Weight Effect of HA on Biological Fate of GO 38
3.1 Introduction 38
3.2 Experimental Section 40
3.3 Results and Discussion 43
3.3.1 Preperation and Characterization of HA-GO Conjugates with Different MW of HA 43
3.3.2 MW-dependent Drug Loading and Releasing 45
3.3.3 MW-dependent In Vitro Cellular Uptake 46
3.3.4 MW-dependent In Vivo Tumor Uptake and Retention 46
3.4 Conclusion 54
3.5 References 55

Chapter4 HA-GO Nanoconjugates for Biomedical Applications 56
4.1 Introduction 56
4.2 Experimental Section 61
4.3 Results and Discussion 70
4.3.1 PDT 70
4.3.2 MiRNA Sensing 82
4.4 Conclusion 89
4.5 References 91

Chapter5 Polysaccharide/GO Composites by Self-Assembly 93
5.1 Introduction 93
5.2 Experiment Section 97
5.3 Results and Discussion 101
5.3.1 Preparation of HA/GO Hydrogel 101
5.3.2 Characterization of Chi/GO LbL Assembly 102
5.3.3 Antibacterial Property of Chi/GO Films 103
5.3.3 Cell Affinity Property of Chi/GO Films 104
5.4 Conclusion 112
1.5 References 113

국문 초록 (Abstract in Korean) 116
dc.format.extent99541329 bytes-
dc.publisher서울대학교 대학원-
dc.subjectgraphene oxide-
dc.subjecthyaluronic acid-
dc.subjecthyrid materials-
dc.subjectbiomedical applications-
dc.titleGraphene Oxide/Polysaccharide Hybrids for Biomedical Applications-
dc.title.alternative생물의학적 응용을 위한 산화그래핀/다당류고분자 복합재료의 제조 및 특성분석-
dc.contributor.affiliation공과대학 화학생물공학부-
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College of Engineering/Engineering Practice School (공과대학/대학원)Dept. of Chemical and Biological Engineering (화학생물공학부)Theses (Ph.D. / Sc.D._화학생물공학부)
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