光療具有創傷小、副作用少、提高癌症治療準確性等優點。為此，我們合成一種由聚多巴胺（PDA）、Zeolitic Imidazole Framework-8（ZIF-8）和包裹熱休克蛋白抑製劑VER-155008組成的多功能奈米顆粒。ZIF-8是一個有應用於生物醫學潛力之新型有機金屬框架（Metal Organic Frameworks, MOFs）。本研究討論了將聚多巴胺修飾的 ZIF-8 和 VER-155008 作為新的協同劑與光熱療法（photothermal therapy, PTT）和光動力療法（photodynamic therapy, PDT）聯合用於殺死癌細胞的應用。PDA@VER/ZIF-8在近紅外（near-infrared, NIR）照射（808 nm）下提供高光熱轉換和活性氧物質（oxygen species, ROS）生成效率，從而導致PDA@VER/ZIF-8在低濃度使MCF-7細胞產生不可逆損傷。使用NIR激光照射PDA@VER/ZIF-8將光子的能量轉化為熱量和ROS。我們的研究結果表明，在VER@ZIF-8表面修飾PDA可以提高PDA@VER/ZIF-8的生物相容性。這項工作將 PTT 和 PDT 效應集成到單個奈米複合材料中，以提供高效的癌症治療。同時，PDA@VER/ZIF-8結合了PDA、VER和ZIF-8的優點，表現出優異的生物相容性、靶向性和抗腫瘤能力，在未來的癌症治療臨床研究中具有巨大的潛力。

　　Phototherapy has the advantages of minimal invasion, few side effects, and improved accuracy for cancer therapy. To this end, we synthesized a multifunctional nanoparticle composed of polydopamine (PDA), Zeolitic Imidazole Framework-8 (ZIF-8), and encased heat shock protein inhibitor VER-155008. ZIF-8 is one of the Metal Organic Frameworks (MOFs) which widely used in biomedicine. The application of a polydopamine modified ZIF-8 and VER-155008 as a new synergistic agent in combination with photothermal therapy (PTT) and photodynamic therapy (PDT) to kill cancer cells is discussed in this study. The PDA@VER/ZIF-8 offered high light-to-heat conversion and oxygen species (ROS) generation efficiency under near-infrared (NIR) irradiation (808 nm), thus leading to irreversible damage to PDA@VER/ZIF-8-treated MCF-7 cells at low concentration. Irradiation of PDA@VER/ZIF-8 using an NIR laser converted the energy of the photons to heat and ROS. Our results showed that modification of the PDA on the surface of VER@ZIF-8 can improve the biocompatibility of the PDA@VER/ZIF-8. This work integrated the PTT and PDT effects into a single nanocomplex to afford a highly efficient cancer treatment. Meanwhile, PDA@VER/ZIF-8, which combines the advantages of PDA, VER and ZIF-8, displayed excellent biocompatibility, targeting, and tumoricidal ability, thus suggesting its huge potential for future clinical research in cancer therapy.

摘要………i
Abstract………ii
誌謝………iii
目錄………iv
表目錄………vi
圖目錄………vii
縮寫對照表………viii
第一章 緒論………1
1.1 前言………1
1.2 研究目的………1
第二章 文獻探討………2
2.1 新型有機金屬框架(Metal Organic Framework)………2
2.2 癌症………3
2.3 小分子抑製劑………5
2.4 多巴胺(dopamine)………5
2.5 光熱治療(photothermal therapy)………6
2.6 光動治療(photodynamic therapy)………7
2.7 凋亡(Apoptosis)………8
2.8 自噬(Autophagy)………9
第三章 實驗架構與材料方法………10
3.1 實驗架構圖………10
3.2 實驗材料………11
3.2.1 實驗藥品………11
3.2.2 實驗儀器………13
3.2.3 實驗細胞………15
3.3 實驗方法………16
3.3.1 VER@ZIF-8製備………16
3.3.2 PDA@ZIF-8製備………16
3.3.3 PDA@VER/ZIF-8製備及定量………16
3.3.4 熱場發射掃描式電子顯微鏡(FE-SEM)………17
3.3.5 動態光散射粒徑分析儀(DLS)………17
3.3.6 傅立葉紅外線光譜(Fourier-transform infrared spectroscopy, FTIR)………17
3.3.7 奈米粒子之VER-155008裝載效率………17
3.3.8 奈米粒子光熱特性………18
3.3.9 奈米粒子之VER-155008釋放效率………19
3.3.10 細胞培養………19
3.3.11 細胞毒性試驗(MTT assay)………19
3.3.12 光熱療………20
3.3.13 細胞活性氧物質試驗(DCFH-DA assay)………20
3.3.14 細胞凋亡試驗(JC-1 Mitochondrial Membrane Potential Detection Kit)………21
3.3.15 細胞自噬檢測(DAPGreen-Autophagy Detection)………21
3.3.16 酵素免疫分析法(Enzyme-Linked Immunosorbent Assay, ELISA)………22
3.3.17 統計分析………22
第四章 結果與討論………23
4.1 奈米粒子物化特性檢測………23
4.1.1 熱場發射掃描式電子顯微鏡(FE-SEM)之粒徑及形貌分析………23
4.1.2 動態光散射粒徑分析儀(DLS)之粒徑分析………24
4.1.3 傅立葉紅外線光譜(Fourier-transform infrared spectroscopy, FTIR)之定性分析………25
4.1.4 奈米粒子之VER-155008裝載效率………26
4.1.5 奈米粒子光熱特性………27
4.1.6 奈米粒子之VER-155008釋放效率………30
4.2 體外細胞實驗………31
4.2.1 細胞毒性試驗(MTT assay)………31
4.2.2 光熱療………33
4.2.3 光動療 - 細胞活性氧物質試驗(DCFH-DA assay)………34
4.2.4 細胞凋亡試驗(JC-1 Mitochondrial Membrane Potential Detection Kit)………35
4.2.5 細胞自噬試驗(DAPGreen-Autophagy Detection)………36
4.2.6 熱休克蛋白保護機制(HSP70) - 酵素免疫分析法(ELISA)………37
第五章 結論………39
參考文獻………40
Extended Abstract………46

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