Responsive image
博碩士論文 etd-0728118-203208 詳細資訊
Title page for etd-0728118-203208
論文名稱
Title
經藍光照射快速凝膠之水凝膠系統應用於腦癌之協同治療
Rapid in situ gelation by blue light-irradiation for combination therapy in brain tumor.
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
95
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2018-08-08
繳交日期
Date of Submission
2018-08-30
關鍵字
Keywords
水凝膠、藥物輸送、光熱治療、腦癌、協同治療、甲基丙烯醯明膠
Hydrogel, Brain tumor, Drug delivery, Combination therapy, Photothermal therapy, Gelatin methylacrylate
統計
Statistics
本論文已被瀏覽 5696 次,被下載 1
The thesis/dissertation has been browsed 5696 times, has been downloaded 1 times.
中文摘要
在美國,腦癌位居二十歲以下人口癌症死因第一名,每年有四萬人被診斷出罹患惡性腦癌,當中有一萬五千名個案屬於預後極差;即使配合化學及放射治療,存活時間中位數僅有 14.6 個月的神經膠質母細胞瘤 (Glioblastoma)。現行的治療方法為手術切除及使用化學藥物,然而前者往往無法取盡癌細胞,後者則在體液內快速被代謝,或是效果不顯著。克服上述腦癌臨床治療之困境,及預防腦癌手術後復發,是相當有挑戰性的課題。有鑑於此,本研究使用明膠 (Gelatin) 此一具有優良生物相容性,且衍生自膠原蛋白 (Collagen) 之天然聚合物作為水凝膠 (Hydrogel) 之骨架,並結合協同治療 (Combination therapy) 之概念,開發一體內快速凝膠、具有良好組織貼附性、應用於雷射間質熱治療 (Laser interstitial thermal therapy , LITT)、放射與化學治療之藍光交聯之水凝膠藥物輸送系統,以預防術後殘存之癌細胞復發及擴散。此研究之目標為:(1) 最佳化水凝膠包覆化學治療藥物泛艾黴素 (Epirubicin) ,與放射敏感劑順鉑 (Cisplatin) 之條件。(2) 研究此水凝膠系統凝膠效率、藥物釋放、雷射熱治療之表現。(3) 以人類癌症細胞及體內腫瘤模型,評估此一水凝膠系統於癌症治療之效果。結果除了證實水凝膠材料與熱治療材料本身無生物毒性之外,並顯示此結合多重治療之水凝膠藥物輸送系統,能藉由緩慢釋放藥物抑或雷射熱治療而造成細胞毒性,於動物實驗之初步結果中,對於異種移植神經膠質肉瘤 (Gliosarcoma) ,如 U87-MGFL 與 MBR-614 之小鼠,能有效抑制其腫瘤增生,並延長其存活時間,相較於對照組存活時間中位數 36 日,施用此水凝膠藥物輸送系統之小鼠其存活時間為 65 日以上。綜合上述,此一協同治療水凝膠藥物輸送系統,提供了局部藥物輸送系統及預防腦瘤復發一相當嶄新且具有前瞻性的途徑。
Abstract
About 40,000 people are diagnosed with primary brain tumors in the United States each year, an estimated 15,000 have glioblastoma multiforme (GBM), still associated with poor prognosis with 14.6 months of median survival after surgical resection combined with chemotherapy and radiation. Preventing tumor from post-surgical recurrence is a significant clinical challenge since current methods deliver chemotherapeutic agents in a rapid manner and are not effective against the residual tumor cells, such as Gliadel® . To overcome this drawback, we develop a blue light-crosslinking hydrogel which can be rapidly gelled in situ and tightly adhere on the tissues for controlled chemotherapy, radiotherapy, and enhanced laser interstitial thermal therapy (LITT) to inhibit residual tumor cells from post-surgical recurrence. The principle goals are to i) determine the prevailing factors that affect efficient encapsulation of chemotherapeutic drugs (i.e., Epirubicin) and radio-sensitizer (i.e., Cisplatin) within hydrogels, ii) demonstrate efficiency of gelation, LITT enhancement, in vitro drug release, iii) evaluate the efficiency in human cancer cells and in vivo tumor model. Thus, we used gelatin, a highly biocompatible material which derived from collagen, as hydrogel scaffold to encapsulate small molecule drug (Epirubicin and Cisplatin). Our results have demonstrated that this multi-treatment system can effectively prevent tumor recurrence and significantly prolong the medium survival of gliosarcoma-bearing (MBR-614 or U87-MGFL) mice to above 65 days compared with the control group (36 days). We believe this synergistic strategy presents a new approach to the development of a local drug delivery system for the prevention of brain tumor recurrence.
目次 Table of Contents
目錄
論文審定書 ................................................................................................................ i
致謝 ........................................................................................................................... ii
摘要 ........................................................................................................................... iii
Abstract .................................................................................................................... iv
圖次 ........................................................................................................................... viii
表次 ........................................................................................................................... ix
縮寫表 ....................................................................................................................... x
第 一 章 、緒論 ...................................................................................................... 1
1.1 腦癌 .................................................................................................................. 1
1.1.1 概況 ............................................................................................................. 1
1.1.2 分類 ............................................................................................................. 3
(1) 依分化程度 ................................................................................................... 3
(2) 依來源及細胞種類 ........................................................................................ 3
1.1.3 治療 ............................................................................................................. 4
(1) 手術切除 ....................................................................................................... 4
(2) 化學治療 ....................................................................................................... 4
(3) 放射線療法 ................................................................................................... 5
(4) 其他治療方式 ............................................................................................... 5
1.1.4 目前臨床療法困境 ..................................................................................... 6
(1) 血腦屏障 ...................................................................................................... 6
(2) 療程困境與副作用 ....................................................................................... 6
(3) 治療花費 ...................................................................................................... 7
1.1.5 當前腦部藥物輸送應用與研究 ...................................................................8
(1) 臨床 BCNU 劑型的改良 ............................................................................... 8
(2) 標靶奈米粒子 ...............................................................................................9
(3) 使用聲孔效應穿隧血腦屏障 .......................................................................10
(4) 水凝膠用於局部藥物釋放 .......................................................................... 11
1.2 水凝膠 ............................................................................................................ 12
1.2.1 簡介 ............................................................................................................12
1.2.2 材質 ........................................................................................................... 13
1.2.3 凝膠方法 ....................................................................................................14
1.2.4 明膠與膠原蛋白 ........................................................................................ 16
(1) 過去應用 ..................................................................................................... 16
(2) 甲基丙烯醯水凝膠 ......................................................................................17
1.3 協同治療 ........................................................................................................18
1.3.1 概念 ...........................................................................................................18
1.3.2 順鉑與泛艾黴素 ........................................................................................19
1.3.3 光熱治療 ................................................................................................... 23
1.4 研究動機與目的 .............................................................................................25
第 二 章 、材料與實驗方法 ................................................................................27
2.1 實驗材料 ........................................................................................................27
2.1.1 藥品與耗材 ...............................................................................................27
(1) 化學藥品與實驗套組 ................................................................................ 27
(2) 耗材用品 ................................................................................................... 29
2.1.2 實驗用細胞 ............................................................................................. 29
2.2 實驗儀器 .......................................................................................................30
2.3 研究方法 ...................................................................................................... 31
2.3.1 水凝膠製備 ............................................................................................. 31
(1) Gelatin 修飾與純化 .................................................................................. 31
(2) 光熱材料合成 ........................................................................................... 32
(3) 藥物及光熱材料裝載 ................................................................................ 34
(4) 光起始凝膠 ............................................................................................... 34
2.3.2 水凝膠鑑定與分析 .................................................................................. 35
(1) 傅立葉轉換紅外光譜與核磁共振光譜 ..................................................... 35
(2) 掃描式電子顯微鏡 ................................................................................... 35
(3) 凝膠時間 .................................................................................................. 36
(4) 熱重損失分析 .......................................................................................... 36
2.3.3 光熱材料鑑定與分析 ............................................................................. 37
(1) 吸收光譜 .................................................................................................. 37
(2) 穿隧式電子顯微鏡影像 ........................................................................... 37
(3) 發熱性質測試 .......................................................................................... 37
(4) 細胞毒性 .................................................................................................. 38
2.3.4 裝載藥物水凝膠之藥物釋放與細胞毒性 ............................................... 39
(1) EPI 釋放性質 .......................................................................................... 39
(2) 細胞毒性測試 ........................................................................................... 40
(3) 細胞螢光影像 ........................................................................................... 41
2.3.5 動物實驗 ................................................................................................. 42
(1) Gelatin MA 於體內凝膠之研究 ................................................................. 42
(2) 光熱效應於動物實驗之研究 ..................................................................... 42
(3) 裝載藥物與光熱材料之水凝膠抑制腫瘤能力 .......................................... 43
第 三 章 、結果與討論 ...................................................................................... 44
3.1 水凝膠鑑定與分析 ....................................................................................... 44
3.1.1 基礎性質分析 ......................................................................................... 44
(1) 化學結構分析 ........................................................................................... 44
(2) 凝膠測試 .................................................................................................. 48
3.1.2 光熱材料分析 ......................................................................................... 50
(1) 物化性質分析 .......................................................................................... 50
(2) 體外發熱性質測試 ................................................................................... 52
(3) 細胞毒性 .................................................................................................. 54
3.2 裝載藥物水凝膠之藥物釋放與細胞毒性 ..................................................... 55
3.2.1 藥物釋放性質 ......................................................................................... 55
3.2.2 細胞毒性測試 ......................................................................................... 57
3.2.3 細胞螢光影像 ......................................................................................... 60
3.3 動物實驗 ...................................................................................................... 62
3.3.1 動物體內凝膠測試 .................................................................................. 62
3.3.2 光熱效應於動物實驗之研究 ................................................................... 64
3.3.3 裝載藥物與光熱材料之水凝膠抑制腫瘤能力 .........................................66
3.4 討論 .............................................................................................................. 71
第 四 章 、結論 ................................................................................................. 77
第 五 章 、參考文獻 ......................................................................................... 78
參考文獻 References
參考文獻
1. Siegel, R. L.; Miller, K. D.; Jemal, A., Cancer statistics, 2017. CA: A Cancer Journal for Clinicians 2017, 7-30.
2. Siegel, R. L.; Miller, K. D.; Jemal, A., Cancer statistics, 2018. CA: A Cancer Journal for Clinicians 2018, 7-30.
3. Davis, M. E., Glioblastoma: Overview of Disease and Treatment. Clinical journal of oncology nursing 2016, S2-S8.
4. 105年度死因統計. Ministry of Health Welfare: Taiwan, 2017.
5. Visser, O.; Ardanaz, E.; Botta, L.; Sant, M.; Tavilla, A.; Minicozzi, P., Survival of adults with primary malignant brain tumours in Europe; Results of the EUROCARE-5 study. European Journal of Cancer 2015, 2231-2241.
6. Wei, K.-C. Brain Tumor.Chang Gung Medical Fundation, Taiwan https://www1.cgmh.org.tw/intr/intr2/c32320/disease-0.asp?pno=58
7. 國家衛生研究院TOCG顱內腫瘤研究委員會, 腦瘤之診斷與治療共識. 2004.
8. DeAngelis, L. M., Brain tumors. The New England Journal of Medicine 2001, 114-123.
9. Doroshenko, N.; Doroshenko, P., The glutathione reductase inhibitor carmustine induces an influx of Ca2+ in PC12 cells. European Journal of Pharmacology 2004, 17-24.
10. Narita, Y., Bevacizumab for glioblastoma. Therapeutics and Clinical Risk Management 2015, 1759-1765.
11. Huang, Y.-C. Treatment of malignant astrocytic tumor : now and future.Chang Gung Medical Fundation, Taiwan https://www1.cgmh.org.tw/intr/intr2/c32320/disease-0.asp?pno=52
12. Wang, P. P.; Frazier, J.; Brem, H., Local drug delivery to the brain. Advanced Drug Delivery Reviews 2002, 987-1013.
13. Wolff, J. E. A.; Berrak, S.; Koontz Webb, S. E.; Zhang, M., Nitrosourea efficacy in high-grade glioma: a survival gain analysis summarizing 504 cohorts with 24193 patients. Journal of Neuro-Oncology 2008, 57-63.
14. De Bonis, P.; Anile, C.; Pompucci, A.; Fiorentino, A.; Balducci, M.; Chiesa, S.; Maira, G.; Mangiola, A., Safety and efficacy of Gliadel wafers for newly diagnosed and recurrent glioblastoma. Acta Neurochirurgica 2012, 1371-1378.
15. Yang, H.-W.; Hua, M.-Y.; Liu, H.-L.; Tsai, R.-Y.; Chuang, C.-K.; Chu, P.-C.; Wu, P.-Y.; Chang, Y.-H.; Chuang, H.-C.; Yu, K.-J.; Pang, S.-T., Cooperative Dual-Activity Targeted Nanomedicine for Specific and Effective Prostate Cancer Therapy. ACS Nano 2012, 1795-1805.
16. Hadjipanayis, C. G.; Machaidze, R.; Kaluzova, M.; Wang, L.; Schuette, A. J.; Chen, H.; Wu, X.; Mao, H., EGFRvIII Antibody–Conjugated Iron Oxide Nanoparticles for Magnetic Resonance Imaging–Guided Convection-Enhanced Delivery and Targeted Therapy of Glioblastoma. Cancer Research 2010, 6303-6312.
17. Pepe, J.; Rincón, M.; Wu, J., Experimental comparison of sonoporation and electroporation in cell transfection applications. Acoustics Research Letters Online 2004, 62-67.
18. Timbie, K. F.; Afzal, U.; Date, A.; Zhang, C.; Song, J.; Wilson Miller, G.; Suk, J. S.; Hanes, J.; Price, R. J., MR image-guided delivery of cisplatin-loaded brain-penetrating nanoparticles to invasive glioma with focused ultrasound. Journal of Controlled Release 2017, 120-131.
19. Hynynen, K.; Chung, A. H.; Colucci, V.; Jolesz, F. A., Potential adverse effects of high-intensity focused ultrasound exposure on blood vessels in vivo. Ultrasound in Medicine & Biology 1996, 193-201.
20. Vinchon-Petit, S.; Jarnet, D.; Paillard, A.; Benoit, J.-P.; Garcion, E.; Menei, P., In vivo evaluation of intracellular drug-nanocarriers infused into intracranial tumours by convection-enhanced delivery: distribution and radiosensitisation efficacy. Journal of Neuro-Oncology 2010, 195-205.
21. Fourniols, T.; Randolph, L. D.; Staub, A.; Vanvarenberg, K.; Leprince, J. G.; Préat, V.; des Rieux, A.; Danhier, F., Temozolomide-loaded photopolymerizable PEG-DMA-based hydrogel for the treatment of glioblastoma. Journal of Controlled Release 2015, 95-104.
22. Ahmed, E. M., Hydrogel: Preparation, characterization, and applications: A review. Journal of Advanced Research 2015, 105-121.
23. Hoffman, A. S., Hydrogels for biomedical applications. Advanced Drug Delivery Reviews 2012, 18-23.
24. Oun, R.; Plumb, J. A.; Wheate, N. J., A cisplatin slow-release hydrogel drug delivery system based on a formulation of the macrocycle cucurbit[7]uril, gelatin and polyvinyl alcohol. Journal of Inorganic Biochemistry 2014, 100–105.
25. Xu, J.; Strandman, S.; Zhu, J. X.; Barralet, J.; Cerruti, M., Genipin-crosslinked catechol-chitosan mucoadhesive hydrogels for buccal drug delivery. Biomaterials 2015, 395-404.
26. Young, S.; Wong, M.; Tabata, Y.; Mikos, A. G., Gelatin as a delivery vehicle for the controlled release of bioactive molecules. Journal of Controlled Release 2005, 256–274.
27. Ta, H. T.; Dass, C. R.; Dunstan, D. E., Injectable chitosan hydrogels for localised cancer therapy. Journal of Controlled Release 2007, 205 – 216.
28. Yue, K.; Trujillo-de Santiago, G.; Alvarez, M. M.; Tamayol, A.; Annabi, N.; Khademhosseini, A., Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials 2015, 254-271.
29. Adams, M. L.; Lavasanifar, A.; Kwon, G. S., Amphiphilic block copolymers for drug delivery. Journal of Pharmaceutical Sciences 2003, 1343–1355
30. Nichol, J. W.; Koshy, S. T.; Bae, H.; Hwang, C. M.; Yamanlar, S.; Khademhosseini, A., Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials 2010, 5536-5544.
31. Ma, H.; He, C.; Cheng, Y.; Yang, Z.; Zang, J.; Liu, J.; Chen, X., Localized Co-delivery of Doxorubicin, Cisplatin, and Methotrexate by Thermosensitive Hydrogels for Enhanced Osteosarcoma Treatment. ACS Applied Materials & Interfaces 2015, 27040-27048.
32. Reddy, N.; Reddy, R.; Jiang, Q., Crosslinking biopolymers for biomedical applications. Trends in Biotechnology 2015, 362-369.
33. Zhang, X. J.; Cai, W. B.; Hao, L. Y.; Hu, X. H.; Wei, X. J.; Wang, X. Y.; Lin, Q., Preparation of thermo/pH-sensitive reduced graphene oxide interpenetrating hydrogel nanocomposites for co-delivery of paclitaxel and epirubicin. Materials Technology 2018, 245-252.
34. Nayak, P. K. Thermal-Responsive Poly(N-Isopropylacrylamide) and its Critical Solution Temperature Type Behavior in Presence of Hydrophilic Ionic Liquids. University of Massachusetts Amherst, Masters Theses, 2015. 165
35. Ruirui, X.; Kai, L.; Tifeng, J.; Ning, Z.; Kai, M.; Ruiyun, Z.; Qianli, Z.; Guanghui, M.; Xuehai, Y., An Injectable Self‐Assembling Collagen–Gold Hybrid Hydrogel for Combinatorial Antitumor Photothermal/Photodynamic Therapy. Advanced Materials 2016, 3669-3676.
36. Gasperini, L.; Mano, J. F.; Reis, R. L., Natural polymers for the microencapsulation of cells. Journal of The Royal Society Interface 2014, 1-19.
37. Sakaguchi M, I. S., Systemic allergic reactions to gelatin included in vaccines as a stabilizer. Japanese journal of infectious diseases 2000, 189-195.
38. Zhao, X.; Wang, J.; Tao, S.; Ye, T.; Kong, X.; Ren, L., In Vivo Bio-distribution and Efficient Tumor Targeting of Gelatin/Silica Nanoparticles for Gene Delivery. Nanoscale Research Letters 2016, 1-9.
39. Van Den Bulcke, A. I.; Bogdanov, B.; De Rooze, N.; Schacht, E. H.; Cornelissen, M.; Berghmans, H., Structural and Rheological Properties of Methacrylamide Modified Gelatin Hydrogels. Biomacromolecules 2000, 31-38.
40. Reza Bayat Mokhtari1, 4, Tina S. Homayouni1, Narges Baluch3, Evgeniya Morgatskaya1, Sushil Kumar1, Bikul Das4 and Herman Yeger1,2, Combination therapy in combating cancer. Oncotarget. 2017, 38022-38043.
41. Han, H. D.; Song, C. K.; Park, Y. S.; Noh, K. H.; Kim, J. H.; Hwang, T.; Kim, T. W.; Shin, B. C., A chitosan hydrogel-based cancer drug delivery system exhibits synergistic antitumor effects by combining with a vaccinia viral vaccine. International Journal of Pharmaceutics 2008, 27-34.
42. Yuan Tang; McGoron, A. J., Combined effects of laser-ICG photothermotherapy and doxorubicin chemotherapy on ovarian cancer cells. Journal of Photochemistry and Photobiology B: Biology 2009, 138–144.
43. Yang, K.; Wan, J.; Zhang, S.; Tian, B.; Zhang, Y.; Liu, Z., The influence of surface chemistry and size of nanoscale graphene oxide on photothermal therapy of cancer using ultra-low laser power. Biomaterials 2012, 2206-2214.
44. Khdair, A.; Handa, H.; Mao, G.; Panyam, J., Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro. European Journal of Pharmaceutics and Biopharmaceutics 2009, 214-222.
45. Wilkins, D. E.; Ng, C. E.; Raaphorst, G. P., Cisplatin and low dose rate irradiation in cisplatin resistant and sensitive human glioma cells. International Journal of Radiation Oncology • Biology • Physics 1996, 105-111.
46. Wong, E. T.; Hess, K. R.; Gleason, M. J.; Jaeckle, K. A.; Kyritsis, A. P.; Prados, M. D.; Levin, V. A.; Yung, W. K. A., Outcomes and Prognostic Factors in Recurrent Glioma Patients Enrolled Onto Phase II Clinical Trials. Journal of Clinical Oncology 1999, 2572-2572.
47. Brandes, A. A.; Basso, U.; Reni, M.; Vastola, F.; Tosoni, A.; Cavallo, G.; Scopece, L.; Ferreri, A. J.; Panucci, M. G.; Monfardini, S.; Ermani, M., First-Line Chemotherapy With Cisplatin Plus Fractionated Temozolomide in Recurrent Glioblastoma Multiforme: A Phase II Study of the Gruppo Italiano Cooperativo di Neuro-Oncologia. Journal of Clinical Oncology 2004, 1598-1604.
48. Stupp, R.; Hegi, M. E.; Mason, W. P.; van den Bent, M. J.; Taphoorn, M. J. B.; Janzer, R. C.; Ludwin, S. K.; Allgeier, A.; Fisher, B.; Belanger, K.; Hau, P.; Brandes, A. A.; Gijtenbeek, J.; Marosi, C.; Vecht, C. J.; Mokhtari, K.; Wesseling, P.; Villa, S.; Eisenhauer, E.; Gorlia, T.; Weller, M.; Lacombe, D.; Cairncross, J. G.; Mirimanoff, R.-O., Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. The Lancet Oncology 2009, 459-466.
49. Dasari, S.; Bernard Tchounwou, P., Cisplatin in cancer therapy: Molecular mechanisms of action. European Journal of Pharmacology 2014, 364-378.
50. Kobayashi, K.; Usami, N.; Porcel, E.; Lacombe, S.; Le Sech, C., Enhancement of radiation effect by heavy elements. Mutation Research/Reviews in Mutation Research 2010, 123-131.
51. Sonali Setua , M. O., Sara G. Piccirillo , Colin Watts and Mark Welland Cisplatin-tethered gold nanospheres for multimodal chemo-radiotherapy of glioblastoma. Nanoscale 2014, 10865-10873.
52. Marcu, L.; van Doorn, T.; Olver, I., Cisplatin and Radiotherapy in the Treatment of Locally Advanced Head and Neck Cancer. Acta Oncologica 2003, 315-325.
53. Howerton, S. B.; Nagpal, A.; Williams, L. D., Surprising roles of electrostatic interactions in DNA-ligand complexes. Biopolymers 2003 87-99.
54. Thorn, C. F.; Oshiro, C.; Marsh, S.; Hernandez-Boussard, T.; McLeod, H.; Klein, T. E.; Altman, R. B., Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenetics and Genomics 2011, 440-446.
55. Yang, F.; Teves, S. S.; Kemp, C. J.; Henikoff, S., Doxorubicin, DNA torsion, and chromatin dynamics. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 2014, 84-89.
56. Takahashi, A.; Ohnishi, K.; Ota, I.; Asakawa, I.; Tamamoto, T.; Furusawa, Y.; Matsumoto, H.; Ohnishi, T., p53 -Dependent thermal enhancement of cellular sensitivity in human squamous cell carcinomas in relation to LET. International Journal of Radiation Biology 2001, 1043-1051.
57. Dewhirst, M. W.; Viglianti, B. L.; Lora-Michiels, M.; Hanson, M.; Hoopes, P. J., Basic principles of thermal dosimetry and thermal thresholds for tissue damage from hyperthermia. International Journal of Hyperthermia 2003, 267-294.
58. Yang, K.; Zhang, S.; Zhang, G.; Sun, X.; Lee, S.-T.; Liu, Z., Graphene in Mice: Ultrahigh In Vivo Tumor Uptake and Efficient Photothermal Therapy. Nano Letters 2010, 3318-3323.
59. Yin, T.; Liu, J.; Zhao, Z.; Zhao, Y.; Dong, L.; Yang, M., Redox Sensitive Hyaluronic Acid-Decorated Graphene Oxide for Photothermally Controlled Tumor-Cytoplasm-Selective Rapid Drug Delivery. Advanced Functional Material 2017, 1-12.
60. Zhu, X.; Zhang, Y.; Huang, H.; Zhang, H.; Hou, L.; Zhang, Z., Functionalized graphene oxide-based thermosensitive hydrogel for near-infrared chemo-photothermal therapy on tumor. Journal of Biomaterials Applications 2016, 1230–1241.
61. Niidome, T.; Yamagata, M.; Okamoto, Y.; Akiyama, Y.; Takahashi, H.; Kawano, T.; Katayama, Y.; Niidome, Y., PEG-modified gold nanorods with a stealth character for in vivo applications. Journal of Controlled Release 2006, 343-347.
62. Lu, W.; Melancon, M. P.; Xiong, C.; Huang, Q.; Elliott, A.; Song, S.; Zhang, R.; Flores, L. G.; Gelovani, J. G.; Wang, L. V.; Ku, G.; Stafford, R. J.; Li, C., Effects of Photoacoustic Imaging and Photothermal Ablation Therapy Mediated by Targeted Hollow Gold Nanospheres in an Orthotopic Mouse Xenograft Model of Glioma. Cancer Research 2011, 6116-6121.
63. Gazotti, W. A.; Juliano, V. F.; De Paoli, M.-A., Thermal and photochemical degradation of dodecylsulfate doped polypyrrole. Polymer Degradation and Stability 1993, 317-321.
64. Chen, M.; Fang, X.; Tang, S.; Zheng, N., Polypyrrole nanoparticles for high-performance in vivo near-infrared photothermal cancer therapy. Chemical Communications 2012, 8934-8936.
65. Mohammadi, A. M.; Hawasli, A. H.; Rodriguez, A.; Schroeder, J. L.; Laxton, A. W.; Elson, P.; Tatter, S. B.; Barnett, G. H.; Leuthardt, E. C., The role of laser interstitial thermal therapy in enhancing progression‐free survival of difficult‐to‐access high‐grade gliomas: a multicenter study. Cancer Medicine 2014, 971-979.
66. Thomas, J. G.; Rao, G.; Kew, Y.; Prabhu, S. S., Laser interstitial thermal therapy for newly diagnosed and recurrent glioblastoma. Neurosurgical Focus 2016, E12.
67. Simpsondag, C. R.; Kohldag, M.; Essenpreis, M.; Cope, M., Near-infrared optical properties of ex vivo human skin and subcutaneous tissues measured using the Monte Carlo inversion technique Physics in Medicine and Biology 1998, 2465-2478.
68. Paola, O.; Roberta, V.; Laura, R.; Laura, C.; Matteo, M.; Marco, R., VA-086 methacrylate gelatine photopolymerizable hydrogels: A parametric study for highly biocompatible 3D cell embedding. Journal of Biomedical Materials Research Part A 2015, 2109-2117.
69. Hoch, E.; Schuh, C.; Hirth, T.; Tovar, G. E. M.; Borchers, K., Stiff gelatin hydrogels can be photo-chemically synthesized from low viscous gelatin solutions using molecularly functionalized gelatin with a high degree of methacrylation. Journal of Materials Science: Materials in Medicine 2012, 2607-2617.
70. Hoch, E.; Hirth, T.; Tovar, G. E. M.; Borchers, K., Chemical tailoring of gelatin to adjust its chemical and physical properties for functional bioprinting. Journal of Materials Chemistry B 2013, 5675-5685.
71. Klein, M. P.; Hackenhaar, C. R.; Lorenzoni, A. S. G.; Rodrigues, R. C.; Costa, T. M. H.; Ninow, J. L.; Hertz, P. F., Chitosan crosslinked with genipin as support matrix for application in food process: Support characterization and β-d-galactosidase immobilization. Carbohydrate Polymers 2016, 184-190.
72. Arya, A. D.; Hallur, P. M.; Karkisaval, A. G.; Gudipati, A.; Rajendiran, S.; Dhavale, V.; Ramachandran, B.; Jayaprakash, A.; Gundiah, N.; Chaubey, A., Gelatin Methacrylate Hydrogels as Biomimetic Three-Dimensional Matrixes for Modeling Breast Cancer Invasion and Chemoresponse in Vitro. ACS Applied Materials & Interfaces 2016, 22005-22017.
73. O'Brien, F. J., Biomaterials & scaffolds for tissue engineering. Materials Today 2011, 88-95.
74. Nicodemus, G. D.; Bryant, S. J., Cell Encapsulation in Biodegradable Hydrogels for Tissue Engineering Applications. Tissue Engineering Part B: Reviews 2008, 149-165.
75. Bagul, D.-S.; Upadhye, D.; Huse, N.; Dive, A.; R. Kasar, R.; Sharma, R., Growth and Ammonia Gas Sensing Study of Nanostructured Polypyrrole Thin Film. Bionano Frontier 2015, 198-200.
76. Liu, J.-H.; Yang, S.-T.; Wang, H.; Chang, Y.; Cao, A.; Liu, Y., Effect of size and dose on the biodistribution of graphene oxide in mice. Nanomedicine 2012, 1801-1812.
77. Candice, L. D.; Pinhas, E.; Astrid, C.-R.; Steven, L. J.; Jeffrey, J. L. C., Depth of photothermal conversion of gold nanorods embedded in a tissue-like phantom. Nanotechnology 2009, 1-9.
電子全文 Fulltext
本電子全文僅授權使用者為學術研究之目的,進行個人非營利性質之檢索、閱讀、列印。請遵守中華民國著作權法之相關規定,切勿任意重製、散佈、改作、轉貼、播送,以免觸法。
論文使用權限 Thesis access permission:自定論文開放時間 user define
開放時間 Available:
校內 Campus: 已公開 available
校外 Off-campus: 已公開 available


紙本論文 Printed copies
紙本論文的公開資訊在102學年度以後相對較為完整。如果需要查詢101學年度以前的紙本論文公開資訊,請聯繫圖資處紙本論文服務櫃台。如有不便之處敬請見諒。
開放時間 available 已公開 available

QR Code