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Tumor angiogenesis imaging using cyclic RGD-PEGylated gold nanoparticles labeled with radioiodine : 방사성 옥소 표지 cRGD-PEG 금 나노 입자를 이용한 종양 신생혈관 영상
DC Field | Value | Language |
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dc.contributor.advisor | 정준기 | - |
dc.contributor.author | 김영화 | - |
dc.date.accessioned | 2017-07-14T01:41:48Z | - |
dc.date.available | 2017-07-14T01:41:48Z | - |
dc.date.issued | 2013-08 | - |
dc.identifier.other | 000000013257 | - |
dc.identifier.uri | https://hdl.handle.net/10371/122253 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 : 의과학과 의과학 전공, 2013. 8. 정준기. | - |
dc.description.abstract | Introduction: The biocompatibility of nanoparticles is important in biomedical field such as in vivo molecular imaging and drug delivery. To visualize the tumor angiogenesis, I developed 125I-labeled gold nanoparticles (AuNPs) conjugated with cyclic RGD-PEG peptides.
Methods: I developed that cyclic RGD-PEGylated-AuNPs was labeled with 125I (125I-cRP-AuNPs) as molecular imaging probes for targeting integrin αvβ3. The stability of 125I-cRP-AuNPs was monitored by ITLC-SG with saline (pH 7) as the solvent for 16 hrs at 37oC in serum. For the competitive binding assay to the integrin αvβ3, 125I-echistatin was incubated with αvβ3-expressing cancer cell, U87MG and non-expressing cancer cell, MCF7 after pre-treating with cRP-AuNPs or cRGD peptides. Cellular uptakes of 125I were measured using gamma-counter. To confirm receptor specific internalization of cRP-AuNPs, TEM image was acquired in U87MG and MCF7 cell lines. The uptake and clearance of 125I-cRP-AuNPs in vivo was evaluated using serial SPECT/CT studies from 0 hr to 5 hrs after intravenous injection of 11.1 MBq 125I-cRP-AuNPs in a U87MG tumor bearing mice. To confirm specific integrin αvβ3 binding of 125I-cRP-AuNPs, the extracted tumor tissues were analyzed by TEM imaging technique and stained with αvβ3 integrin antibody. Renal clearance of 125I-cRP-AuNPs was confirmed with radio-TLC analysis of urine samples after injection. Results: The entire 125I labeling procedure to cyclic RGD-PEGylated gold nanoparticles was completed within 20 min including purification and concentration steps. Radio-chemical purity of 125I-labeled cRGD-AuNPs was very stable during the incubation in serum at 37oC. In competitive binding assay to U87MG cells, IC50 values for cRP-AuNPs and cRGD peptides were 0.33 nM and 51.34 nM, respectively. Remarkably, the 125I-cRP-AuNP probes showed ~150-fold higher αvβ3 avidity than the corresponding cRGD peptides. TEM images showed intracellular localization of the particles in U87MG cells only, not in MCF7 cells. SPECT/CT image showed uptakes of 125I-cRP-AuNPs in the U87MG xenografted tumor and blood pool until 1 hr after injection. In the extracted tumor analysis, the TEM images clearly showed the 125I-cRP-AuNPs are uptake by the tumor. And the tumor tissue was well correlated with αvβ3-PE staining regions and Au silver enhancement. These results demonstrate that the 125I-cRP-AuNPs entered the tumor via integrin αvβ3-receptor specific endocytosis. Radio-chemical yield of urine samples was observed over 50% of 125I-cRP-AuNPs, this result showed their efficient clearance from the body through renal and urinary excretion route. Conclusion: 125I-cRP-AuNPs defined αvβ3 expressing cancer cells both in vitro and in vivo. These functionalized 125I-cRP-AuNPs have a visualization in tumor and angiogenesis which will be useful for various diagnostic and therapeutic applications. | - |
dc.description.tableofcontents | CONTENTS
Abstract i List of Figures and Tables v List of Abbreviations vii Introduction 1 Material and Methods 6 Results 20 Discussion 50 References 55 Abstract in Korean 64 | - |
dc.format | application/pdf | - |
dc.format.extent | 3663480 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | gold nanoparticles | - |
dc.subject | nanoparticle toxicity | - |
dc.subject | tumor angiogenesis targeting | - |
dc.subject | tumor angiogenesis imaging | - |
dc.subject | integrin αvβ3 | - |
dc.subject | iodine-125 | - |
dc.subject | SPECT/CT | - |
dc.subject.ddc | 610 | - |
dc.title | Tumor angiogenesis imaging using cyclic RGD-PEGylated gold nanoparticles labeled with radioiodine | - |
dc.title.alternative | 방사성 옥소 표지 cRGD-PEG 금 나노 입자를 이용한 종양 신생혈관 영상 | - |
dc.type | Thesis | - |
dc.description.degree | Doctor | - |
dc.citation.pages | vii, 66 | - |
dc.contributor.affiliation | 의과대학 의과학과 | - |
dc.date.awarded | 2013-08 | - |
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