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Peptide-functionalized graphene as a tumor-activable theranostic system : 펩타이드 수식 그래핀을 이용한 종양조직 활성화 진단/치료 시스템
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 오유경 | - |
dc.contributor.author | 최선희 | - |
dc.date.accessioned | 2017-07-19T11:25:59Z | - |
dc.date.available | 2017-07-19T11:25:59Z | - |
dc.date.issued | 2017-02 | - |
dc.identifier.other | 000000140754 | - |
dc.identifier.uri | https://hdl.handle.net/10371/133655 | - |
dc.description | 학위논문 (석사)-- 서울대학교 대학원 : 약학대학 약학과(물리약학전공), 2017. 2. 오유경. | - |
dc.description.abstract | Simultaneous cancer therapy and diagnosis, termed theranostics, have received considerable attention due to requirement of personalized medicine, fulfilling spatiotemporal needs of medication for individual patient. Here, we developed a tumor selectively-activable theranostic system that utilize a conjugate of Cy5.5, polyethylene glycol (PEG), and chimeric peptide which engineered to include a matrix metalloproteinase (MMP)-cleavable sequence, a spacer sequence, and a binding sequence for graphene nanosheet (GN). Cy5.5-PEG-chimeric peptide-modified GN clearly marred the fluorescence of Cy5.5 and cell-penetrating function of therapeutic peptide modified onto GN due to quenching ability of GN, and stealth effect of PEG, respectively. With the presence of MMP, cleavage of chimeric peptide released Cy5.5-PEG from GN, facilitating recovery of fluorescence of Cy5.5 and exposure of cell penetrating peptide on the surface of GN. Deletion of MMP-cleavable sequence in this theranostic system showed negligible differences in fluorescence and antitumor effect upon exposure to MMP. Intravenous administration of MMP-cleavable PEG-GN into SCC7 tumor-bearing mice resulted in 7.2-fold higher fluorescence intensity at tumor site than that of MMP-non-cleavable PEG-GN after 24 hours. Furthermore, cell-penetrating peptide delivered by MMP-cleavable PEG-GN revealed the highest antitumor effect, showing 80% regression of tumor volume than untreated group. Overall, our results demonstrate that tumor-activable PEG-GN could serve as a nano-theranostic system for tumor selective imaging and therapy. | - |
dc.description.tableofcontents | 1. Introduction 1
2. Materials and methods 4 2.1. Synthesis of peptides 4 2.2. Detection of peptide cleavage 5 2.3. Preparation of surface functionalized GN 6 2.4. Characterization 7 2.5. Dequenching ability test of pMSP-GN 8 2.6. Loading of T-Bu onto nanosheets 8 2.7. Hemolysis assay 9 2.8. In vitro anti-cancer efficacy test 9 2.9. In vivo fluorescence imaging study 10 2.10. In vivo anti-cancer efficacy test 11 3. Results 12 3.1. Characterization of pMSP-GN nanoplatform 12 3.2. Dequenching of fluorescence following cleavage of peptide 12 3.3. In vitro anti-tumor effect 18 3.4. In vivo imaging by fluorescence distribution of pMSP-GN 18 3.5. In vivo anti-tumor effect of T-Bu delivered on pMSP-GN 21 4. Discussion 24 5. Conclusion 26 6. References 27 국문 초록 30 | - |
dc.format | application/pdf | - |
dc.format.extent | 2405121 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | theranostics | - |
dc.subject | graphene nanosheet | - |
dc.subject | tumor microenvironment | - |
dc.subject | matrix metalloproteinase | - |
dc.subject | anticancer effect | - |
dc.subject.ddc | 615 | - |
dc.title | Peptide-functionalized graphene as a tumor-activable theranostic system | - |
dc.title.alternative | 펩타이드 수식 그래핀을 이용한 종양조직 활성화 진단/치료 시스템 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Sunhee Choi | - |
dc.description.degree | Master | - |
dc.citation.pages | 31 | - |
dc.contributor.affiliation | 약학대학 약학과 | - |
dc.date.awarded | 2017-02 | - |
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