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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 劉如熹(Ru-Shi Liu) | |
| dc.contributor.author | Chiao-Ling Cheng | en |
| dc.contributor.author | 鄭巧翎 | zh_TW |
| dc.date.accessioned | 2021-06-07T17:33:30Z | - |
| dc.date.copyright | 2020-07-02 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-06-22 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/15379 | - |
| dc.description.abstract | 血腦屏障(blood-brain barrier)為一層由內皮細胞、星狀膠細胞與基底膜緊密連接所組成之「障壁」，可選擇性阻止某些物質由血液進入大腦內。此屏障僅可使必要之小分子物質，如，氧氣、胺基酸、葡萄糖與水通過，此屏障且將藥物與蛋白質等大分子隔絕在外。該屏障保護腦部不受病菌感染，卻亦使顱內治療難以實現。 為使藥物能有效送入腦部且治療腦內多形性腦瘤(glioblastoma，又稱膠質母細胞瘤)。本研究以可受超音波震盪產生空穴效應(cavitation)之奈米氣泡，包埋藥物並結合長餘輝奈米粒子，投遞至大腦進行腦瘤治療與追蹤。該複合材料經超音波處理後，氣泡因內部氣體介質不同於液體環境而產生空穴效應，可暫時性打開血腦屏障，將化療藥物帝盟多(temozolomide)與近紅外發光之長餘輝奈米粒子送入腦內進行藥物治療。因長餘輝奈米粒子具長時間放光與高訊雜比，其可穿透深層組織提高生物影像之解析度。於體內治療中，藉奈米複合材料治療後之腫瘤體積，較控制組減少約90％之腫瘤體積，並降低小鼠死亡率至17%，於原位治療中，藉Ki67與TUNEL組織學研判，奈米複合材料可大幅降低膠質母細胞瘤之Ki67蛋白表現且觀察其細胞凋亡現象，故本研究開發之奈米複合材料可突破血腦屏障進行藥物投遞，且能長時間追蹤腦部影像，以達有效評估腦癌之治療效果。 | zh_TW |
| dc.description.abstract | The blood-brain barrier (BBB) is a physical barrier composed of endothelial cells, astrocytes and the basement membrane, which can selectively prevent certain substances from crossing the blood to the brain. BBB protects the brain from germs and causes difficulty in intracranial treatment. The nanomaterial which composed of the chemotherapy drug temozolomide (TMZ) embedded in nanobubbles (NB), persistent luminescent nanoparticles (PLN) and aptamer AS1411 (AAp) is used to treat glioblastoma. Through ultrasound induction, NBs produce cavitation that temporarily opens the BBB. In addition, PLNs release near-infrared emission and afterglow, which can penetrate deep tissues and improve the signal-to-noise ratio of bioimages. In the in vivo treatment, the tumor volume after treatment with nanocomposite material is reduced about 90% compared with the control group, and the mouse mortality rate is reduced to 17%. In the in situ treatment, Ki67 and TUNEL immunohistochemistry can be used to judge the nanocomposite material. The expression of Ki67 protein of the tumor after treatment with nanocomposite material is significantly reduced. The TUNEL can be used to observe the apoptosis of the tumor. Therefore, the nanocomposite material developed in this research can break through the BBB for drug delivery, and can track brain images for a long time to effectively evaluate the therapeutic effect on glioblastoma. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-07T17:33:30Z (GMT). No. of bitstreams: 1 U0001-2206202015310400.pdf: 7590922 bytes, checksum: 802b78afab852f3205c3557d1ccafe8f (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 目錄 口試委員會審定書 I 誌謝 II 摘要 III Abstract IV 目錄 V 圖目錄 IX 表目錄 XIII 英文縮寫表 XIV 第一章 緒論 1 1.1膠質母細胞瘤之簡介 1 1.1.1血腦屏障 1 1.1.2膠質母細胞瘤之治療與標靶 3 1.2 超音波之簡介 4 1.2.1超音波之醫學成像 5 1.2.2 超音波之顯影劑 6 1.3 奈米藥物載體之簡介 7 1.3.1奈米氣泡 10 1.3.2空穴效應 11 1.3.3 高滲透長滯留效應 12 1.4 近紅外光之長餘輝奈米粒子之簡介 13 1.4.1 近紅外光窗口 14 1.4.2 長餘輝放光之原理 15 1.4.3 長餘輝奈米粒子之生物應用 17 1.5 奈米複合材料之應用 19 1.6 研究動機與目的 23 第二章 實驗步驟與儀器分析原理 25 2.1 化學藥品 26 2.2 實驗步驟 28 2.2.1 近紅外光長餘輝奈米粒子之合成 28 2.2.2 帝盟多藥物包埋於奈米氣泡之合成 29 2.2.3 奈米氣泡與長餘輝奈米粒子之組裝 30 2.2.4 奈米複合材料與核酸適體之合成 30 2.2.5 生物分布學(biodistribution) 31 2.2.6 聚丙烯醯胺凝膠電泳(polyacrylamide gel electrophoresis; PAGE gel) 31 2.2.7 共軛焦顯微鏡細胞顯影(confocal cell imaging) 32 2.2.8 西方點墨法(western blot) 32 2.2.9 細胞生物相容性與毒殺測試(cell viablity and toxicity assay) 32 2.2.10 活體實驗(in vivo tests) 33 2.2.11 組織染色(hematoxylin and eosin stain; H E stain) 33 2.2.12 原位實驗(in situ tests) 34 2.2.13免疫染色(immunohistochemistry; IHC) 35 2.3 儀器原理 35 2.3.1 X光粉末繞射儀(x-ray powder diffraction microscopy; XRD) 35 2.3.2掃描式電子顯微鏡(scanning electron microscope; SEM) 36 2.3.3穿透式電子顯微鏡(transmission electron microscope; TEM) 37 2.3.4感應耦合電漿放射光譜儀(inductively coupled plasma optical emission spectrometer; ICP-OES) 38 2.3.5比表面積與孔隙度分析儀(specific surface area and porosimetry analyzer) 39 2.3.6傅立葉轉換紅外光譜儀(Fourier-transform infrared spectrometer; FTIR) 42 2.3.7光激發光光譜儀(photoluminescence spectrometer; PL) 43 2.3.8絕對量子效率儀(absolute photoluminescence quantum yield spectrometer; QY) 44 2.3.9奈米粒徑與界面電位量測儀(dynamic light scattering and zeta potential analyzer) 45 2.3.10紫外光/可見光吸收光譜儀(ultraviolet visible spectrophotometer; UV-Vis) 47 2.3.11超音波均質機(sonicator) 47 2.3.12超音波診斷儀(ultrasound scanner) 48 2.3.13雷射掃描共軛聚焦顯微鏡(laser scanning confocal microscopy; LSCM) 49 2.3.14流式細胞儀(flow cytometer) 50 2.3.15非侵入式活體分子影像系統(non invasion in vivo imaging system; IVIS) 51 第三章 結果與討論 52 3.1奈米複合材料之鑑定 52 3.1.1 近紅外光長餘輝奈米粒子之結構與形貌鑑定 52 3.1.2 近紅外光長餘輝奈米粒子之表面性質分析 56 3.1.3 近紅外光長餘輝奈米粒子之光學性質分析 58 3.1.4 奈米氣泡之形貌與表面性質鑑定 61 3.1.5 帝盟多藥物包埋於奈米氣泡之載藥比率探討 62 3.1.6 奈米複合材料之結構形貌與表面性質鑑定 64 3.2 應用於膠質母細胞瘤治療之奈米複合材料 66 3.2.1 奈米複合材料之標靶蛋白與核酸適體探討 67 3.2.2 奈米複合材料之細胞影像與標靶能力探討 68 3.2.3 奈米複合材料之細胞相容性與細胞毒殺效果 70 3.2.4 奈米複合材料之體內治療效果與腫瘤組織切片探討 71 3.2.5 奈米複合材料之腦部原位治療效果與免疫切片探討 74 第四章 結論 77 參考文獻 78 | |
| dc.language.iso | zh-TW | |
| dc.subject | 藥物傳遞 | zh_TW |
| dc.subject | 膠質母細胞瘤 | zh_TW |
| dc.subject | 長餘暉奈米粒子 | zh_TW |
| dc.subject | 奈米氣泡 | zh_TW |
| dc.subject | Glioblastoma | en |
| dc.subject | drug delivery | en |
| dc.subject | nanobubble | en |
| dc.subject | persistent luminescent nanoparticle | en |
| dc.title | 紅外線奈米粒子之合成及其應用於超音波引導腦部膠質母細胞瘤治療 | zh_TW |
| dc.title | Synthesis and Application of Infrared Nanoparticles Ultrasound-guided Glioblastoma Treatment in the Brain | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蕭宏昇(Michael Hsiao),方俊民(Jim-Min Fang),黃鵬林(Pung-Ling Huang),鍾仁傑(Ren-Jei Chung) | |
| dc.subject.keyword | 膠質母細胞瘤,長餘暉奈米粒子,奈米氣泡,藥物傳遞, | zh_TW |
| dc.subject.keyword | Glioblastoma,persistent luminescent nanoparticle,nanobubble,drug delivery, | en |
| dc.relation.page | 85 | |
| dc.identifier.doi | 10.6342/NTU202001103 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2020-06-23 | |
| dc.contributor.author-college | 理學院 | zh_TW |
| dc.contributor.author-dept | 化學研究所 | zh_TW |
| 顯示於系所單位： | 化學系 | |
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