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A Targeting Strategy to Overcome Tumor Heterogeneity Using Polymerized Metabolic Precursors

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Authors
정슬희
Advisor
안철희
Major
공과대학 재료공학부
Issue Date
2015-08
Publisher
서울대학교 대학원
Keywords
Polymerized Metabolic PrecursorsTumor HeterogeneityMetabolic GlycoengineeringClick ChemsitryOptical Imaging
Description
학위논문 (석사)-- 서울대학교 대학원 : 재료공학부, 2015. 8. 안철희.
Abstract
Historically, drug as a free form has been directly used in cancer treatment. However, while the anticancer drugs can be distributed throughout the whole body, it is very toxic and causes many side effects to normal tissues. To overcome this problem, many nano-technologies have been applied for an effective delivery of anticancer drugs to the targeting cancer cells. In this study, we developed polymerized metabolic precursor (pMPs) to improve tumor-targeting abilities. Furthermore, the pMPs is designed to overcome the intrinsic limitations causing from the limited amount of cellular receptors and the heterogeneity of tumor cells. The pMPs are based on metabolic glycoengineering and click chemistry. Triacetylated N-azidoacetyl-D-mannosamine (Ac3ManNAz) is conjugated to the PAMAM [G4] dendrimer backbone and the compound generates azide groups on the surface of tumor tissue specifically. Regardless of tumor cell types, pMPs create a more uniform cancer cells with artificial glycans on their surface. With the enhanced permeation and retention (EPR) effect followed by metabolic glycoengineering, the pMPs generate receptor-like chemical reporters to produce a homogeneous cancer cell surface in the tumor tissue. Then, they can be labeled by ADIBO-Cy5.5 via copper-free click chemistry in vivo condition.
Language
English
URI
https://hdl.handle.net/10371/123358
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College of Engineering/Engineering Practice School (공과대학/대학원)Dept. of Materials Science and Engineering (재료공학부)Theses (Master's Degree_재료공학부)
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