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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76434完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 何佳安 | |
| dc.contributor.author | Yu-Fu Chen | en |
| dc.contributor.author | 陳郁夫 | zh_TW |
| dc.date.accessioned | 2021-07-09T15:52:18Z | - |
| dc.date.available | 2022-09-12 | |
| dc.date.copyright | 2017-09-12 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-08-18 | |
| dc.identifier.citation | 1. Chidambaram, M., Manavalan, R. & Kathiresan, K. Nanotherapeutics to overcome conventional cancer chemotherapy limitations. J Pharm Pharm Sci 14, 67-77 (2011).
2. Widakowich, C., de Castro, G., Jr., de Azambuja, E., Dinh, P. & Awada, A. Review: side effects of approved molecular targeted therapies in solid cancers. Oncologist 12, 1443-1455, doi:10.1634/theoncologist.12-12-1443 (2007). 3. Quail, D. F. & Joyce, J. A. Microenvironmental regulation of tumor progression and metastasis. Nat Med 19, 1423-1437, doi:10.1038/nm.3394 (2013). 4. Mbeunkui, F. & Johann, D. J., Jr. Cancer and the tumor microenvironment: a review of an essential relationship. Cancer Chemother Pharmacol 63, 571-582, doi:10.1007/s00280-008-0881-9 (2009). 5. Gilkes, D. M., Bajpai, S., Chaturvedi, P., Wirtz, D. & Semenza, G. L. Hypoxia- inducible factor 1 (HIF-1) promotes extracellular matrix remodeling under hypoxic conditions by inducing P4HA1, P4HA2, and PLOD2 expression in fibroblasts. J Biol Chem 288, 10819-10829, doi:10.1074/jbc.M112.442939 (2013). 6. Gilkes, D. M. et al. Collagen prolyl hydroxylases are essential for breast cancer metastasis. Cancer Res 73, 3285-3296, doi:10.1158/0008-5472.CAN-12-3963 (2013). 7. Gilkes, D. M. & Semenza, G. L. Role of hypoxia-inducible factors in breast cancer metastasis. Future Oncol 9, 1623-1636, doi:10.2217/fon.13.92 (2013). 8. Chen, F. et al. New horizons in tumor microenvironment biology: challenges and opportunities. BMC Med 13, 45, doi:10.1186/s12916-015-0278-7 (2015). 9. Zhen, Z. et al. Protein Nanocage Mediated Fibroblast-Activation Protein Targeted Photoimmunotherapy To Enhance Cytotoxic T Cell Infiltration and Tumor Control. Nano Lett 17, 862-869, doi:10.1021/acs.nanolett.6b04150 (2017). 10. Kobayashi, H., Watanabe, R. & Choyke, P. L. Improving conventional enhanced permeability and retention (EPR) effects; what is the appropriate target? Theranostics 4, 81-89, doi:10.7150/thno.7193 (2013). 11. Gajewski, T. F., Schreiber, H. & Fu, Y. X. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol 14, 1014-1022, doi:10.1038/ni.2703 (2013). 12. Lindau, D., Gielen, P., Kroesen, M., Wesseling, P. & Adema, G. J. The immunosuppressive tumour network: myeloid-derived suppressor cells, regulatory T cells and natural killer T cells. Immunology 138, 105-115, doi:10.1111/imm.12036 (2013). 13. Dijkgraaf, E. M. et al. Chemotherapy alters monocyte differentiation to favor generation of cancer-supporting M2 macrophages in the tumor microenvironment. Cancer Res 73, 2480-2492, doi:10.1158/0008-5472.CAN-12-3542 (2013). 14. Blum, J. S., Wearsch, P. A. & Cresswell, P. Pathways of antigen processing. Annu Rev Immunol 31, 443-473, doi:10.1146/annurev-immunol-032712-095910 (2013). 15. Tang, X., Mo, C., Wang, Y., Wei, D. & Xiao, H. Anti-tumour strategies aiming to target tumour-associated macrophages. Immunology 138, 93-104, doi:10.1111/imm.12023 (2013). 16. Solinas, G., Germano, G., Mantovani, A. & Allavena, P. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol 86, 1065-1073, doi:10.1189/jlb.0609385 (2009). 17. Kurahara, H. et al. Significance of M2-polarized tumor-associated macrophage in pancreatic cancer. J Surg Res 167, e211-219, doi:10.1016/j.jss.2009.05.026 (2011). 18. Mantovani, A., Germano, G., Marchesi, F., Locatelli, M. & Biswas, S. K. Cancer- promoting tumor-associated macrophages: new vistas and open questions. Eur J Immunol 41, 2522-2525, doi:10.1002/eji.201141894 (2011). 19. Qian, B. Z. & Pollard, J. W. Macrophage diversity enhances tumor progression and metastasis. Cell 141, 39-51, doi:10.1016/j.cell.2010.03.014 (2010). 20. Sica, A. & Mantovani, A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 122, 787-795, doi:10.1172/JCI59643 (2012). 21. Biswas, S. K. & Mantovani, A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol 11, 889-896, doi:10.1038/ni.1937 (2010). 22. Klinman, D. M. Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat Rev Immunol 4, 249-258, doi:10.1038/nri1329 (2004). 23. Traves, P. G., Luque, A. & Hortelano, S. Macrophages, inflammation, and tumor suppressors: ARF, a new player in the game. Mediators Inflamm 2012, 568783, doi:10.1155/2012/568783 (2012). 24. Allavena, P., Sica, A., Solinas, G., Porta, C. & Mantovani, A. The inflammatory micro-environment in tumor progression: the role of tumor-associated macrophages. Crit Rev Oncol Hematol 66, 1-9, doi:10.1016/j.critrevonc.2007.07.004 (2008). 25. Binnemars-Postma, K., Storm, G. & Prakash, J. Nanomedicine Strategies to Target Tumor-Associated Macrophages. Int J Mol Sci 18, doi:10.3390/ijms18050979 (2017). 26. Panni, R. Z., Linehan, D. C. & DeNardo, D. G. Targeting tumor-infiltrating macrophages to combat cancer. Immunotherapy 5, 1075-1087, doi:10.2217/imt.13.102 (2013). 27. Cho, K., Wang, X., Nie, S., Chen, Z. G. & Shin, D. M. Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res 14, 1310-1316, doi:10.1158/1078- 0432.CCR-07-1441 (2008). 28. Davis, M. E., Chen, Z. G. & Shin, D. M. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 7, 771-782, doi:10.1038/nrd2614 (2008). 29. Draz, M. S. et al. Nanoparticle-mediated systemic delivery of siRNA for treatment of cancers and viral infections. Theranostics 4, 872-892, doi:10.7150/thno.9404 (2014). 30. Chahibi, Y., Akyildiz, I. F. & Sang Ok, S. Antibody-based molecular communication for targeted drug delivery systems. Conf Proc IEEE Eng Med Biol Soc 2014, 5707-5710, doi:10.1109/EMBC.2014.6944923 (2014). 31. Gilboa, E., Berezhnoy, A. & Schrand, B. Reducing Toxicity of Immune Therapy Using Aptamer-Targeted Drug Delivery. Cancer Immunol Res 3, 1195-1200, doi:10.1158/2326-6066.CIR-15-0194 (2015). 32. Fan, N. C., Cheng, F. Y., Ho, J. A. & Yeh, C. S. Photocontrolled targeted drug delivery: photocaged biologically active folic acid as a light-responsive tumor- targeting molecule. Angew Chem Int Ed Engl 51, 8806-8810, doi:10.1002/anie.201203339 (2012). 33. Tao, Y. et al. Engineered, self-assembled near-infrared photothermal agents for combined tumor immunotherapy and chemo-photothermal therapy. Biomaterials 35, 6646-6656, doi:10.1016/j.biomaterials.2014.04.073 (2014). 34. Zhang, S., Gao, H. & Bao, G. Physical Principles of Nanoparticle Cellular Endocytosis. ACS Nano 9, 8655-8671, doi:10.1021/acsnano.5b03184 (2015). 35. Chen, N. T. et al. Theranostic applications of mesoporous silica nanoparticles and their organic/inorganic hybrids. J Mater Chem B 1, 3128-3135, doi:10.1039/c3tb20249f (2013). 36. Lehar, J. et al. Synergistic drug combinations tend to improve therapeutically relevant selectivity. Nat Biotechnol 27, 659-666, doi:10.1038/nbt.1549 (2009). 37. Bracci, L., Schiavoni, G., Sistigu, A. & Belardelli, F. Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale- based combined treatments against cancer. Cell Death Differ 21, 15-25, doi:10.1038/cdd.2013.67 (2014). 38. Vanneman, M. & Dranoff, G. Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer 12, 237-251, doi:10.1038/nrc3237 (2012). 39. Iwasaki, A. & Medzhitov, R. Toll-like receptor control of the adaptive immune responses. Nat Immunol 5, 987-995, doi:10.1038/ni1112 (2004). 40. Kawai, T. & Akira, S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11, 373-384, doi:10.1038/ni.1863 (2010). 41. Bachelder, E. M. et al. In vitro analysis of acetalated dextran microparticles as a potent delivery platform for vaccine adjuvants. Mol Pharm 7, 826-835, doi:10.1021/mp900311x (2010). 42. Lee, J. et al. Molecular basis for the immunostimulatory activity of guanine nucleoside analogs: activation of Toll-like receptor 7. Proc Natl Acad Sci U S A 100, 6646-6651, doi:10.1073/pnas.0631696100 (2003). 43. Chinnery, H. R., Leong, C. M., Chen, W., Forrester, J. V. & McMenamin, P. G. TLR9 and TLR7/8 activation induces formation of keratic precipitates and giant macrophages in the mouse cornea. J Leukoc Biol 97, 103-110, doi:10.1189/jlb.3AB0414-216R (2015). 44. Saint-Jean, M., Knol, A. C., Nguyen, J. M., Khammari, A. & Dreno, B. TLR expression in human melanoma cells. Eur J Dermatol 21, 899-905, doi:10.1684/ejd.2011.1526 (2011). 45. Kawai, T. & Akira, S. Signaling to NF-kappaB by Toll-like receptors. Trends Mol Med 13, 460-469, doi:10.1016/j.molmed.2007.09.002 (2007). 46. Zhang, G. & Ghosh, S. Toll-like receptor-mediated NF-kappaB activation: a phylogenetically conserved paradigm in innate immunity. J Clin Invest 107, 13- 19, doi:10.1172/JCI11837 (2001). 47. Somani, N. & Rivers, J. K. Imiquimod 5% cream for the treatment of actinic keratoses. Skin Therapy Lett 10, 1-6 (2005). 48. Schon, M. P. & Schon, M. TLR7 and TLR8 as targets in cancer therapy. Oncogene 27, 190-199, doi:10.1038/sj.onc.1210913 (2008). 49. Hoesel, B. & Schmid, J. A. The complexity of NF-kappaB signaling in inflammation and cancer. Mol Cancer 12, 86, doi:10.1186/1476-4598-12-86 (2013). 50. Lawrence, T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol 1, a001651, doi:10.1101/cshperspect.a001651 (2009). 51. Smith, K. J., Hamza, S. & Skelton, H. Topical imidazoquinoline therapy of cutaneous squamous cell carcinoma polarizes lymphoid and monocyte/macrophage populations to a Th1 and M1 cytokine pattern. Clin Exp Dermatol 29, 505-512, doi:10.1111/j.1365-2230.2004.01593.x (2004). 52. Schon, M. et al. Tumor-selective induction of apoptosis and the small-molecule immune response modifier imiquimod. J Natl Cancer Inst 95, 1138-1149 (2003). 53. Sohn, K. C. et al. Imiquimod induces apoptosis of squamous cell carcinoma (SCC) cells via regulation of A20. PLoS One 9, e95337, doi:10.1371/journal.pone.0095337 (2014). 54. Chollet, J. L. et al. Development of a topically active imiquimod formulation. Pharm Dev Technol 4, 35-43, doi:10.1080/10837459908984222 (1999). 55. Chosidow, O. & Dummer, R. Imiquimod: mode of action and therapeutic potential. Acta Derm Venereol Suppl (Stockh), 8-11 (2003). 56. Peters, K. B. & Brown, J. M. Tirapazamine: a hypoxia-activated topoisomerase II poison. Cancer Res 62, 5248-5253 (2002). 57. Wilson, W. R. & Hay, M. P. Targeting hypoxia in cancer therapy. Nat Rev Cancer 11, 393-410, doi:10.1038/nrc3064 (2011). 58. Durand, R. E. & Olive, P. L. Evaluation of bioreductive drugs in multicell spheroids. Int J Radiat Oncol Biol Phys 22, 689-692 (1992). 59. Durand, R. E. & Olive, P. L. Physiologic and cytotoxic effects of tirapazamine in tumor-bearing mice. Radiat Oncol Investig 5, 213-219, doi:10.1002/(SICI)1520- 6823(1997)5:5<213::AID-ROI1>3.0.CO;2-0 (1997). 60. Brown, J. M. & Wilson, W. R. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 4, 437-447, doi:10.1038/nrc1367 (2004). 61. Farkona, S., Diamandis, E. P. & Blasutig, I. M. Cancer immunotherapy: the beginning of the end of cancer? BMC Med 14, 73, doi:10.1186/s12916-016-0623- 5 (2016). 62. Mahoney, K. M., Rennert, P. D. & Freeman, G. J. Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov 14, 561-584, doi:10.1038/nrd4591 (2015). 63. Sharma, P., Wagner, K., Wolchok, J. D. & Allison, J. P. Novel cancer immunotherapy agents with survival benefit: recent successes and next steps. Nat Rev Cancer 11, 805-812, doi:10.1038/nrc3153 (2011). 64. Ginhoux, F. & Jung, S. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol 14, 392-404, doi:10.1038/nri3671 (2014). 65. Chanmee, T., Ontong, P., Konno, K. & Itano, N. Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment. Cancers 6, 1670-1690, doi:10.3390/cancers6031670 (2014). 66. Noy, R. & Pollard, J. W. Tumor-associated macrophages: from mechanisms to therapy. Immunity 41, 49-61, doi:10.1016/j.immuni.2014.06.010 (2014). 67. Vignali, D. A. & Kuchroo, V. K. IL-12 family cytokines: immunological playmakers. Nat Immunol 13, 722-728, doi:10.1038/ni.2366 (2012). 68. Lechner, M., Lirk, P. & Rieder, J. Inducible nitric oxide synthase (iNOS) in tumor biology: the two sides of the same coin. Semin Cancer Biol 15, 277-289, doi:10.1016/j.semcancer.2005.04.004 (2005). 69. Liu, M., Guo, S. & Stiles, J. K. The emerging role of CXCL10 in cancer (Review). Oncol Lett 2, 583-589, doi:10.3892/ol.2011.300 (2011). 70. Jablonski, K. A. et al. Novel Markers to Delineate Murine M1 and M2 Macrophages. PLoS One 10, e0145342, doi:10.1371/journal.pone.0145342 (2015). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76434 | - |
| dc.description.abstract | 過去治療癌症通常是以化療藥物直接去毒殺癌症細胞,然而這樣的方式對於癌症 治療有諸多的限制及副作用產生,這可能是由於化療藥物的非專一性、腫瘤本身產 生的抗藥性及腫瘤環境血管分佈複雜等情形而產生。因此在近年來,科學家們轉而 將治療癌症的目光放在了腫瘤周邊的各微環境因子,希望藉由調控不同微環境因 子去達到更佳的抗癌治療策略。
在本題目中,我所針對的腫瘤微環境因子有二,其一為腫瘤環境中的巨噬細胞群, 在腫瘤環境中,巨噬細胞會分化為兩種截然不同的型態,一種為 M1 型態,在早先 的研究中,它被認為是一種會促進發炎反應的巨噬細胞型態,也因此被認為是一種 能促進免疫反應的巨噬細胞; 而另一種型態為 M2 型態,是在腫瘤環境中較常見的 巨噬細胞型態,其被認為是一種能促進組織修復及抗免疫反應的巨噬細胞型態,因 此在我自己的題目中,想藉由給予免疫調節藥物使腫瘤環境的巨噬細胞,分化為類 似於 M1 的巨噬細胞,以達到免疫治療癌細胞的效果。 另一個我想針對的腫瘤微環境因子為低氧環境,在整個腫瘤中存在著一些血管 難以到達的地方,這些地方的癌細胞由於長期處於缺氧環境下,產生了較強的轉移 能力及抗藥性,因此若使用傳統化療策略可能將無法根治這些區域的癌細胞,導致 療程失敗,在此我想利用一個處於低氧環境才會被活化的前驅藥物來專一性的清 除位於低氧環境的癌細胞,希望能藉此避免產生對處於正常氧環境的正常細胞的 副作用,同時也能根除這些難以清除的癌細胞。 在此,我使用了矽奈米載體同時裝載低氧環境前驅藥物跟免疫調節藥物,一方 面轉變腫瘤環境巨噬細胞型態,另一方面則可以毒殺處於低氧環境的癌細胞,來達 到免疫治療及化療的效果,並期望結合兩者促成更強大的協同效應來治療癌症。 在實驗方面,我們先以動態光散射確認載體在載藥後的大小,且也確認了藥物 裝載效率為何;在細胞實驗中我們測試了奈米劑型化藥物的效果,我們先以MTT assay測試並發現裝載於載體中的低氧環境前驅藥物能夠達到更強的癌細胞毒殺能 力,且用q-PCR及flow cytometry證實免疫調節藥物裝載於載體中能持續地使巨噬細 胞轉變為M1-like 巨噬細胞。 在細胞實驗中我們已經確定了裝載於載體的兩種藥物均能達到原本的效用,最 後在活體實驗上,我們可以看到兩種藥物奈米劑型化為單一載體後對於腫瘤的生 長能力確實有抑制的作用,而且效果目前看來是比 free drug 形式來的更好的。 | zh_TW |
| dc.description.abstract | Chemotherapy is a category of traditional cancer treatment that uses one or more anti- cancer drugs as part of a standardized chemotherapy regimen to eliminate tumor cells, but its major problems including identification of the dose for best anti-tumor effect, and minimization of unpleasant adverse effect. In recent years, tumor microenviroment (TME) has caught a lot of attention in improving therapeutic efficiency for cancer. Tumor- associated macrophages (TAMs) are one of the major factors affecting tumor microenvironment, and two types of macrophages, M1 and M2- type, are found in the TME. M1-type macrophages are anti-tumor macrophages; however, macrophages reside in the TME are often M2-type, which function in promoting the tumor growth through the release of anti-inflammatory cytokines. Therefore, the regulation of the M1:M2 ratio may be a novel, effective and smart strategy for the anti-cancer strategy. Furthermore the hypoxia stands as another key microenvironmental factor regulating multiple phenomenon associated with tumor progression. In this study, silica mesoporous nanoparticles (MSNs) were used to deliver multiple drugs (a hypoxia-activated prodrug and an immunomodulator) via the enhanced permeability and retention (EPR). This combinational strategy was anticipated to inhibit tumor growth and concurrently activate
the immune system, leading to the production of tumor-specific CD8+ T cells. The brilliance of our newly designed combination therapy is to prevent the formation of secondary tumor by induction of the immune memory. Our preliminary results showed that hypoxia-activated prodrug was able to inhibit Lewis lung carcinoma (LLC2) growth in hypoxia condition, and immunomodulator was sufficient to induce polarization of M1- type macrophages. Also, we verified that our nanodrug exhibited better efficiency in growth inhibition of LLC2 and M1 polarization. In summary, this silica based combination therapeutic strategy holds the promising potential for clinical use. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-09T15:52:18Z (GMT). No. of bitstreams: 1 ntu-106-R04b22037-1.pdf: 2935092 bytes, checksum: f3ab7feffef6dd0f647b6be39ff7032a (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | 謝誌................................................................................................................................... I
中文摘要........................................................................................................................ IV 英文摘要........................................................................................................................ VI 第一章 緒論.................................................................................................................... 1 1.1 前言........................................................................................................................ 1 1.2 腫瘤微環境...........................................................................................................2 1.3 傳統化學治療癌症之限制...................................................................................4 1.3.1 存在於低氧環境的癌細胞特性及其導致的化學療法限制........................4 1.3.2 腫瘤環境中的免疫細胞和化療治療限制的關聯........................................6 1.3.3 腫瘤相關巨噬細胞(Tumor-Associated Macrophage, TAM)................... 7 1.3.4 針對巨噬細胞的療法..................................................................................10 1.4 解決腫瘤環境對化學療法的限制.....................................................................12 1.4.1 奈米載體......................................................................................................12 1.4.2 多孔洞矽奈米顆粒(Mesoporous silica nanoparticles, MSN)................ 13 1.4.3 結合療法......................................................................................................16 1.5 Imiquimod (IMQ)................................................................................................. 17 1.6 Tirapazamine (TPZ)............................................................................................. 19 第二章 實驗材料與儀器.............................................................................................. 21 2.1 藥品試劑.............................................................................................................21 2.1.1 細胞實驗......................................................................................................21 2.2 實驗儀器.............................................................................................................23 2.3細胞株.................................................................................................................24 2.4 氣體.....................................................................................................................24 第三章 實驗方法.......................................................................................................... 25 3.1 載體粒徑測量-動態光散射粒徑分析儀 Dynamic Light Scattering Analyzer (DLS).......................................................................................................................... 25 3.2 Tirapazamine(TPZ)之裝載效率(Encapsulation efficiency, EE).................... 25 3.3 Imiquimod(IMQ) 之裝載效率(Encapsulation efficiency, EE) ..................... 26 3.4 細胞實驗.............................................................................................................26 3.4.1 細胞培養......................................................................................................26 3.4.2 細胞繼代......................................................................................................27 3.4.3 細胞冷凍保存..............................................................................................28 3.4.4 細胞解凍......................................................................................................28 3.4.5 缺氧環境培養細胞的作法..........................................................................29 3.4.6 免疫細胞的分化方法..................................................................................29 3.5 細胞存活率實驗(MTT assay)....................................................................... 30 3.6 細胞計數.............................................................................................................31 3.6.1 血球計數器..................................................................................................31 3.6.2 Nexcelon Cellometer Auto T4 自動細胞計數............................................. 31 3.7 基因表現量測試.................................................................................................32 3.8 流式細胞儀(Flow cytometry): 表面抗原辨識(surface marker recognition).............................................................................................................. 34 3.9 動物實驗設計.....................................................................................................34 第四章 實驗動機與設計.............................................................................................. 36 4.1 實驗動機.............................................................................................................36 4.2 實驗設計.............................................................................................................37 第五章 實驗結果.......................................................................................................... 38 5.1 矽奈米顆粒 MSN 能有效裝載兩種疏水性藥物.............................................. 38 5.2 奈米劑型化之低氧環境前驅藥 Tirapazamine(TPZ)對癌細胞株 LL/2 的生長 有較強的抑制能力.................................................................................................... 39 5.3 奈米劑型化之低氧環境前驅藥物 Tirapazamine(TPZ)對 M2 型態巨噬細胞 的生長有較強的抑制能力........................................................................................ 41 5.4 奈米劑型化之免疫調節藥物 Imiquimod(IMQ)可促使處於 M2 型態變化中的 巨噬細胞轉換為趨向 M1 型態的巨噬細胞............................................................ 43 5.5 動物活體實驗:TPZ+IMQ複合藥物之奈米劑型能有效抑制腫瘤生長.......52 5.6 結論.....................................................................................................................54 第六章 討論與未來展望.............................................................................................. 56 第七章 參考文獻......................................................................................................... 57 | |
| dc.language.iso | zh-TW | |
| dc.subject | 藥物傳輸系統 | zh_TW |
| dc.subject | 腫瘤微環境 | zh_TW |
| dc.subject | 免疫治療 | zh_TW |
| dc.subject | immunotherapy | en |
| dc.subject | tumor microenviroment | en |
| dc.subject | drug delivery system | en |
| dc.title | 利用二氧化矽奈米顆粒裝載抗癌藥物發展的新型態癌症結合療法 | zh_TW |
| dc.title | Development of a novel silica based combination therapy with antitumor drug utility | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 徐士蘭,楊家銘,鄭建中,廖明淵,陳平 | |
| dc.subject.keyword | 腫瘤微環境,免疫治療,藥物傳輸系統, | zh_TW |
| dc.subject.keyword | tumor microenviroment,immunotherapy,drug delivery system, | en |
| dc.relation.page | 64 | |
| dc.identifier.doi | 10.6342/NTU201703741 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2017-08-18 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| dc.date.embargo-lift | 2022-09-12 | - |
| 顯示於系所單位： | 生化科技學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-106-R04b22037-1.pdf | 2.87 MB | Adobe PDF | 檢視/開啟 |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。