S-Space College of Engineering/Engineering Practice School (공과대학/대학원) Dept. of Chemical and Biological Engineering (화학생물공학부) Theses (Ph.D. / Sc.D._화학생물공학부)
Graphene Oxide/Polysaccharide Hybrids for Biomedical Applications
생물의학적 응용을 위한 산화그래핀/다당류고분자 복합재료의 제조 및 특성분석
- 차 국 헌
- 공과대학 화학생물공학부
- Issue Date
- 서울대학교 대학원
- graphene oxide; polysaccharides; hyaluronic acid; chitosan; hyrid materials; biomedical applications
- 학위논문 (박사)-- 서울대학교 대학원 : 화학생물공학부, 2015. 2. 차국헌.
- Graphene 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
a 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.