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DNA nanostructure-based systems for drug and nucleic acid delivery : DNA 나노구조 기반 약물 전달 연구
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 오유경 | - |
dc.contributor.author | 김미경 | - |
dc.date.accessioned | 2017-07-13T16:36:31Z | - |
dc.date.available | 2017-07-13T16:36:31Z | - |
dc.date.issued | 2015-08 | - |
dc.identifier.other | 000000066862 | - |
dc.identifier.uri | https://hdl.handle.net/10371/120107 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 : 약학과 약제과학전공, 2015. 8. 오유경. | - |
dc.description.abstract | Rolling circle amplification (RCA)-based DNA nanotechnologies have attracted tremendous interest to develop new platform of drug delivery. First, DNA nanoballs with antisense oligonucleotide (ASO)-complementary sequences could provide sequence-specific loading of dual ASOs, Dz13 and OGX-427, and coating with hyaluronic acid (HA) promoted CD44 receptor-mediated delivery of ASOs to tumor cells. Importantly, ASOs delivered by HA-coated DNA nanoballs silenced the expression of their target mRNAs of ASO, exerting potent anticancer effects in vitro and in vivo. Second, DNA polyaptamer nanothreads of protein tyrosine kinase 7 (PTK7) receptor were synthesized by RCA. To enhance the anchoring capability of polyaptamers onto reduced graphene oxide (rGO), oligonucleotide bridge sequence between repeating aptamer sequences was introduced. Surface modification of rGO with DNA polyaptamer nanothreads (PNTrGO) resulted in improved cellular uptake into PTK7-positive tumor cell lines and enhanced tumor tissue accumulation compared to oligoT-bridged scrambled polyaptamer-anchored rGO nanosheets. Moreover, systemic administration of doxorubicin using PNTrGO enhanced the antitumor effects in mice bearing PTK7-positive tumors. Third, an injectable hydrogel based on drug-specific DNA polyaptamer networks was developed by using graphene oxide (GO) nanosheets as a crosslinker. Graphene oxide-crosslinked DNA polyaptamer (GO-PA) hybrid hydrogels were constructed by running single step RCA of DNA template in the presence of GO nanosheet. GO-PA hybrid hydrogel showed drug-specificity towards kanamycin. The drug loading efficiency of GO-PA was 58.0 % for kanamycin, but 1.2% for gentamicin. | - |
dc.description.tableofcontents | Abstract ii
Contents iv List of Tables vi List of Figures vii List of Abbreviations ix Chapter I. Overview 1. Introduction 2 2. Biomedical applications of RCA-based nanotechnologies 5 3. RCA-based nucleic acid nanostructures for drug delivery 10 4. Scope of the studies 14 5. References 17 Chapter II. Biomimetic DNA nanoballs for oligonucleotide delivery 1. Introduction 27 2. Materials and methods 29 3. Results 36 4. Discussion 51 5. References 55 Chapter III. Polyaptamer DNA nanothread-anchored, reduced graphene oxide nanosheets for targeted delivery 1. Introduction 60 2. Materials and methods 62 3. Results 71 4. Discussion 85 5. References 89 Chapter IV. Polyaptamer DNA and graphene oxide hybrid hydrogel 1. Introduction 94 2. Materials and methods 96 3. Results 102 4. Discussion 112 5. References 116 Conclusion 120 국문 초록 122 | - |
dc.format | application/pdf | - |
dc.format.extent | 3297925 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | DNA nanostructures | - |
dc.subject | rolling circle amplification | - |
dc.subject | drug delivery | - |
dc.subject | aptamer | - |
dc.subject | graphene oxide | - |
dc.subject | reduced graphene oxide | - |
dc.subject.ddc | 615 | - |
dc.title | DNA nanostructure-based systems for drug and nucleic acid delivery | - |
dc.title.alternative | DNA 나노구조 기반 약물 전달 연구 | - |
dc.type | Thesis | - |
dc.description.degree | Doctor | - |
dc.citation.pages | IV, 116 | - |
dc.contributor.affiliation | 약학대학 약학과 | - |
dc.date.awarded | 2015-08 | - |
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