S-Space College of Engineering/Engineering Practice School (공과대학/대학원) Dept. of Material Science and Engineering (재료공학부) Theses (Master's Degree_재료공학부)
Water Soluble Polymerized Metabolic Precursors Based on PEG-PAMAM-Ac3ManNAz System for Epigenetic Targeting
- 공과대학 재료공학부
- Issue Date
- 서울대학교 대학원
- Tumor Heterogeneity; Metabolic Glycoengineering; Epigenetic Targeting; Copper-Free Click Chemistry; Linear-Dendritic Block Copolymer; Self-Assembly
- 학위논문 (석사)-- 서울대학교 대학원 공과대학 재료공학부, 2017. 8. 안철희.
- Over the past several decades, various drug delivery systems have been studied to minimize the side effects of anticancer agents and to increase delivery efficiency to cancer. Despite the development of numerous targeting moiedties, several obstacles remain. Tumor heterogeneity and quantitative limitation of targeted biomolecules are reasons why chemotherapy failed to suppress cancers completely.
In this study, we developed hydrolysable polymerized metabolic precursors (pMPs) by conjugating PEG-PAMAM linear dendritic block copolymers (LDBC) and triacetylated N-azidoacetyl-mannosamine (Ac3ManNAz) via Steglich esterification. As the carboxylic acids of the dendron disappear, pMPs became amphiphilic block copolymers and formed self assembly of 150 nm in aqueous condition. Regardless of genetic phenotypes of tumor cells, pMPs can generate receptor-like azide groups on the cancer cell surface. Furthermore, the azide groups were visualized by ADIBO-Cy5.5 via copper-free click chemistry in vitro condition. It is expected that pMPs have synergy with the enhanced premeability and retention (EPR) effect and hypersialylation of tumor cells to enable tumor cell specific glycan labeling in vivo condition.