Publications
Detailed Information
Tumor microenvironment specific nanostructure-based drug delivery : 종양미세환경 특이적 나노구조체 기반 약물전달
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 오유경 | - |
dc.contributor.author | 진혜림 | - |
dc.date.accessioned | 2018-11-12T01:01:28Z | - |
dc.date.available | 2018-11-12T01:01:28Z | - |
dc.date.issued | 2018-08 | - |
dc.identifier.other | 000000152743 | - |
dc.identifier.uri | https://hdl.handle.net/10371/143324 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 : 약학대학 약학과, 2018. 8. 오유경. | - |
dc.description.abstract | Tumor microenvironment (TME) is composed of tumor tissue and its related immune cells, extracellular matrix and secreted proteins. TME is one of the critical factors for disease treatment and it has been attracting the interest of scientists. Targeted drug delivery originally has the highly expressed proteins on tumor cells and its targetable range has been expanded to TME. Recently, TME specific targeted drug delivery has been rising as promising strategy for improving anticancer treatment efficiency and the applicable field is getting bigger. First, DNA nanostructure was formed by self-assembly suing successive 15 guanine sequence extended to the end of DNA aptamer sequence which can specifically bind to protein tyrosine Kinase 7 (PTK7). Methylene blue (MB) was loaded into the G-quadruplex based DNA nanostructure and the complex showed significantly high delivery effect only to PTK7 overexpressing cancer cells. Then the LED irradiation was followed to generate reactive oxygen species (ROS) and resulting in effective cancer cell killing. Secondly, chlorin e6 (Ce6) having cyclic peptide was designed for loading onto reduced graphene oxide (rGO) nanosheets. The peptide was delivered to and cleaved at cathepsin L enzyme-rich TME.Then targetable peptide was activated to recognized the cancer cell surface proteins and receptor mediated endocytosis occurred. NIR irradiation generated hyperthermia at rGO accumulated tumor cell. The photothermal therapy (PTT) showed complete tumor ablation. Lastly, tight junction (TJ) was selected for targeted drug delivery. TJ is the main protein which limits drug delivery to center of tumor mass. TJ binding peptide was loaded onto rGO nanosheets and the TJ disruption-mediated drug delivery efficiency was evaluated in cell spheroid models and tumor bearing mice models. Keywords: Tumor microenvironment, targeted drug delivery, DNA nanostructure, reduced graphene oxide, photodynamic therapy, photothermal therapy, tight junction, penetration depth | - |
dc.description.tableofcontents | Chapter Ⅰ. Overview 1
1. Introduction 2 2. Tumor microenvironment 4 3. Active drug delivery system 9 4. Scope of the studies 14 5. References 16 Chapter Ⅱ. Stemmed DNA nanostructure for selective delivery of therapeutics 34 1. Introduction 35 2. Materials and methods 37 3. Results 46 4. Discussion 71 5. References 76 Chapter Ⅲ. Serial-controlled delivery of nanomaterials by sequential activation in tumor microenvironment 83 1. Introduction 84 2. Materials and methods 86 3. Results 97 4. Discussion 118 5. References 121 Chapter Ⅳ. Enhanced delivery of nanomaterials by overcoming inter-cellular junction at tumor microenvironment 126 1. Introduction 127 2. Materials and methods 129 3. Results 139 4. Discussion 156 5. References 160 Conclusion 165 국문초록 167 | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject.ddc | 615 | - |
dc.title | Tumor microenvironment specific nanostructure-based drug delivery | - |
dc.title.alternative | 종양미세환경 특이적 나노구조체 기반 약물전달 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Hyerim Jin | - |
dc.description.degree | Doctor | - |
dc.contributor.affiliation | 약학대학 약학과 | - |
dc.date.awarded | 2018-08 | - |
- Appears in Collections:
- Files in This Item:
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.