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    ๊ธˆ/์€ ๋นˆ ๊ณต๊ฐ„ ๋‚˜๋…ธ์‰˜์˜ ํ์•” ์„ธํฌ ํ‘œ๋ฉด ์ถ•์ ์„ ์ด์šฉํ•œ ํŠน์ • ์„ธํฌ ํƒ์ง€ ๊ธฐ๋Šฅ์„ฑ ๊ทผ์ ์™ธ์„  ์œ ๋„์•ฝ๋ฌผ ๋ฐฉ์ถœ ๋ฐ ๊ด‘์—ด ์น˜๋ฃŒ ํšจ๊ณผ

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    ํ•™์œ„๋…ผ๋ฌธ (๋ฐ•์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ์œตํ•ฉ๊ณผํ•™๊ธฐ์ˆ ๋Œ€ํ•™์› : ์œตํ•ฉ๊ณผํ•™๋ถ€ ๋‚˜๋…ธ์œตํ•ฉ์ „๊ณต, 2015. 8. ์กฐ๋ช…ํ–‰.Au/Ag hollow nanoshells (AuHNSs) were developed as multifunctional therapeutic agents for effective, targeted, photothermally induced drug delivery under near-infrared (NIR) light. AuHNSs were synthesized by galvanic replacement reaction. We further conjugated antibodies against the epidermal growth factor receptor (EGFR) to the PEGylated AuHNS, followed by loading with the antitumor drug doxorubicin (AuHNS-EGFR-DOX) for lung cancer treatment. AuHNSs showed similar photothermal efficiency to gold nanorods under optimized NIR laser power. The targeting of AuHNS-EGFR-DOX was confirmed by light-scattering images of A549 cells, and doxorubicin release from the AuHNSs was evaluated under low pH and NIR-irradiated conditions. Multifunctional AuHNS-EGFR-DOX induced photothermal ablation of the targeted lung cancer cells and rapid doxorubicin release following irradiation with a NIR laser. Furthermore, we evaluated the effectiveness of AuHNS-EGFR-DOX drug delivery by comparing two drug delivery methods: receptor-mediated endocytosis and cell-surface targeting. Accumulation of the NPs on the cell surfaces by targeting EGFR demonstrated more effective for lung cancer treatments than uptake of AuHNS-EGFR-DOX. Taken together, our data suggest a new and optimal method of NIR-induced drug release, via the accumulation of targeted AuHNS-EGFR-DOX on cancer cell membranes.Abstract I Table of Contents III List of Figures VI List of Schemes VIII List of Abbreviation IX Introduction 2 1. Nanosystem for biological application and drug delivery 2 2. Nanocarriers for drug delivery by photothermal therapy and chemo-thermo therapy 4 3. Research objective : Development of drug delivery methods with Au/Ag hollow nanoshell (AuHNS) by targeting cancer cells 7 Materials and Methods 9 1. Materials 9 2. Cell culture 10 3. Preparation of Au/Ag hollow-nanoshells (AuHNSs) 10 4. Preparation of AuHNS-EGFR antibody 12 5. Loading of doxorubicin on AuHNS 12 6. Characterization of AgNS and AuHNS 13 7. Verification of photothermal properties of AuHNS 13 8. Cytotoxicity assay 14 9. HRP detection of AuHNS and AuHNS-EGFR 15 10. Western blotting 15 11. Dark field imaging of EGFR conjugated AuHNS 16 12. Doxorubicin release from AuHNS 17 13. Cell viability assay of nanoparticles 17 14. Comparisons of doxorubicin release 18 15. TEM images of AuHNS-EGFR-DOX treated cells 19 16. Data analysis 20 Results and 21 1. Synthesis and characteristics of AuHNS 21 2. Photothermal property of PEGylated AuHNS 28 3. Synthesis of AuHNS-EGFR-DOX 34 4. Targeting efficiencies of AuHNS-EGFR and AuHNS-EGFR-DOX 36 5. Drug releasing abilities of AuHNS-EGFR-DOX 40 6. Mechanism of drug delivery system I: receptor-mediated endocytosis 45 7. Mechanism of drug delivery system II: targeted and accumulated AuHNS-EGFR-DOX on the cell 48 8. Verifications of cellular uptake and targeting of AuHNS-EGFR-DOX 57 Conclusion 61 References 62 ๊ตญ๋ฌธ ๋…ผ๋ฌธ ์ดˆ๋ก 72Docto
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