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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 謝銘鈞(Ming-Jium Shieh) | |
| dc.contributor.author | Ting-Yi Wu | en |
| dc.contributor.author | 吳亭儀 | zh_TW |
| dc.date.accessioned | 2021-06-17T04:42:25Z | - |
| dc.date.available | 2023-08-19 | |
| dc.date.copyright | 2018-08-19 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-08-06 | |
| dc.identifier.citation | 1. Chabner, B.A. and T.G. Roberts, Jr., Timeline: Chemotherapy and the war on cancer. Nat Rev Cancer, 2005. 5(1): p. 65-72.
2. Gottesman, M.M., Mechanisms of cancer drug resistance. Annu Rev Med, 2002. 53: p. 615-27. 3. Liu, F.S., Mechanisms of Chemotherapeutic Drug Resistance in Cancer Therapy-a Quick Review. Taiwanese Journal of Obstetrics & Gynecology, 2009. 48(3): p. 239-244. 4. Canti, G., et al., Antitumor efficacy of the combination of photodynamic therapy and chemotherapy in murine tumors. Cancer Lett, 1998. 125(1-2): p. 39-44. 5. Dolmans, D.E.J.G.J., D. Fukumura, and R.K. Jain, Photodynamic therapy for cancer. Nature Reviews Cancer, 2003. 3(5): p. 380-387. 6. Dolmans, D.E., D. Fukumura, and R.K. Jain, Photodynamic therapy for cancer. Nat Rev Cancer, 2003. 3(5): p. 380-7. 7. Bechet, D., et al., Nanoparticles as vehicles for delivery of photodynamic therapy agents. Trends in Biotechnology, 2008. 26(11): p. 612-621. 8. Brown, S.B., E.A. Brown, and I. Walker, The present and future role of photodynamic therapy in cancer treatment. Lancet Oncol, 2004. 5(8): p. 497-508. 9. Ishikawa, K., et al., ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science, 2008. 320(5876): p. 661-664. 10. Castano, A.P., T.N. Demidova, and M.R. Hamblin, Mechanisms in photodynamic therapy: part one-photosensitizers, photochemistry and cellular localization. Photodiagnosis and Photodynamic Therapy, 2004. 1(4): p. 279-293. 11. Robertson, C.A., D.H. Evans, and H. Abraharnse, Photodynamic therapy (PDT): A short review on cellular mechanisms and cancer research applications for PDT. Journal of Photochemistry and Photobiology B-Biology, 2009. 96(1): p. 1-8. 12. Bielack, S.S., et al., Doxorubicin: effect of different schedules on toxicity and anti-tumor efficacy. Eur J Cancer Clin Oncol, 1989. 25(5): p. 873-82. 13. Faivre, S., et al., Molecular basis for sunitinib efficacy and future clinical development. Nature Reviews Drug Discovery, 2007. 6(9): p. 734-745. 14. Buzdar, A.U., et al., Clinical Course of Patients with Breast-Cancer with 10 or More Positive Nodes Who Were Treated with Doxorubicin-Containing Adjuvant Therapy. Cancer, 1992. 69(2): p. 448-452. 15. Ahmad, I., et al., Antibody-Targeted Delivery of Doxorubicin Entrapped in Sterically Stabilized Liposomes Can Eradicate Lung-Cancer in Mice. Cancer Research, 1993. 53(7): p. 1484-1488. 16. Gordon, A.N., et al., Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol, 2004. 95(1): p. 1-8. 17. Mizutani, H., et al., Mechanism of apoptosis induced by doxorubicin through the generation of hydrogen peroxide. Life Sciences, 2005. 76(13): p. 1439-1453. 18. Mushlin, R.D.O.a.P.S., Doxorubicin cardiotoxicity: analysis of prevailing hypotheses., in The FASEB Journal. 1990. p. 3076-3086. 19. Mena, A.C., E.G. Pulido, and C. Guillen-Ponce, Understanding the molecular-based mechanism of action of the tyrosine kinase inhibitor: sunitinib. Anticancer Drugs, 2010. 21 Suppl 1: p. S3-11. 20. Gotink, K.J., et al., Lysosomal sequestration of sunitinib: a novel mechanism of drug resistance. Clin Cancer Res, 2011. 17(23): p. 7337-46. 21. Nowak-Sliwinska, P., et al., Photoactivation of lysosomally sequestered sunitinib after angiostatic treatment causes vascular occlusion and enhances tumor growth inhibition. Cell Death Dis, 2015. 6: p. e1641. 22. Bingxin Xue, Y.W., XiaoHai Tang, Ping Xie, Yujun Wang, Feng Lu, Chunjie Wu, and Zhiyong Qian, Biodegradable Self-Assembled MPEG-PCL Micelles for Hydrophobic Oridonin Delivery In Vitro, in Journal of Biomedical Nanotechnology. 2012. 23. Chou, T.C., Drug Combination Studies and Their Synergy Quantification Using the Chou-Talalay Method. Cancer Research, 2010. 70(2): p. 440-446. 24. Nel, A.E., et al., Understanding biophysicochemical interactions at the nano-bio interface. Nature Materials, 2009. 8(7): p. 543-557. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70886 | - |
| dc.description.abstract | 癌症長年為全國十大死因之首，許多在初期有效的抗癌藥物會隨著治療時間越久，癌細胞產生突變產生抗藥性而失效，為了有效治療癌症，聯合療法為目前研究致力的方向。在此實驗，我們想藉由藥物載體同時包覆藥物Doxorubicin及Sunitinib(sutent)，透過藥物Doxorubicin達到藥物化學治療效果，以及藥物Sutent照射特殊波段光源產生ROS來達到光動力治療效果。Doxorubicin為現今常見的化療藥物，其作用機制為抑制DNA合成，常用於治療血癌、乳癌等其他各種癌症。Sutent為一種能抑制多種與腫瘤生長及血管生成相關的酪胺酸激酶受體的小分子化合物，會累積在細胞中溶酶體內，近期被發現此藥物同時也具有光感藥物性質，在照射特定波長光源後可以產生ROS以治療腫瘤細胞。然而此藥物的最佳吸收波長為430nm，此波段光源能夠抵達照射的範圍較短，在進行光動力治療上會造成很大的限制，為了改善其缺點，我們使用了雙光子雷射光源，讓原子或分子同時吸收兩個光子而躍遷到高能階，進而激發光動力藥物，達到腫瘤治療的效果。 | zh_TW |
| dc.description.abstract | Combination therapy has become a new trend in oncology since its potential to improve treatment response, minimize development of resistance or adverse events. Herein, we report a nanoparticle encapsulate two anti-cancer drugs to achieve synergic therapeutic efficiency of photodynamic therapy and chemotherapy through two-photon laser. Due to its high bio-compatibility and excellent bio-degeadability, mPEG-PCL was utilized as drug delivery vehicle material. Doxorubicin (DOX) and sunitinib (sutent) were both encapsulated in empty mPEG-PCL micelles as sutent/DOX NPs and achieve Enhanced Permeability and Retention (EPR) effect to accumulate in tumor. As to the results, the sutent/DOX NPs were with an average diameter around 110nm and the encapsulated efficiency were more than 60%. Morphology was further confirmed by TEM image. In addition, sutent/DOX NPs showed a great ability to generate ROS after exposed to a specific region of laser. However, obstacles for the region of laser to activate sutent is with low permeability and not ease to achieve the tumor. Two-photon laser was utilized in the experiment according to its high permeability compare to the normal 430nm laser. MCF-7 cells and MCF-7/ADR cells were utilized in the in vitro experiments. Experiments about DOX IC50 was measured to ensure the drug resistance of MCF-7/ADR cells. Regarding to the cell viability test, sutent/DOX NPs triggerd by laser were quite efficient to kill the MCF-7/ADR cells. As a result, the co-loaded nanoparticles would simultaneously achieve PDT treatment and chemotherapy effect to kill drug-resistant cancer cells. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T04:42:25Z (GMT). No. of bitstreams: 1 ntu-107-R04548055-1.pdf: 1712743 bytes, checksum: 1110b99b5c732907365959677dcfd5a5 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | CONTENTS
ABSTRACT i 中文摘要 iii CONTENTS iv Chapter1 Introduction 1 1.1 Drug resistant cancer 1 1.2 Photodynamic therapy and chemo-therapy 1 1.3 Doxorubicin and sunitinib 2 1.4 Aim 3 Chapter2 Materials and Methods 4 2.1 Materials 4 2.2 Synthesis of mPEG-PCL 4 2.3 Preparation of blank mPEG-PCL nanoparticles and drug-loaded nanoparticles 5 2.4 Characterization of prepared nanoparticles 6 2.5 Releasing profile of drug-loaded nanoparticles 7 2.6 Cell culture 7 2.7 Differences of Dox IC50 between MCF-7 and MCF-7/ADR cells 8 2.8 Combine index 8 2.9 In vitro cellular uptake 9 2.10 In vitro Cytotoxicity of Blank Nanoparticles 10 2.11 ROS detection 10 2.12 Cell viability 11 2.13 Two photon laser excitation 11 2.14 Animals and Tumor model 12 2.15 Statistical analysis 12 Chapter3 Results and Discussion 13 3.1 Characterization of prepared nanoparticles 13 3.2 Stability test 14 3.3 Differences of Dox IC50 between MCF-7 and MCF-7/ADR cells 14 3.4 CI index of free drugs 15 3.5 Cellular uptake 15 3.7 Cytotoxicity of blank micelles 15 3.8 Cell viability 16 3.9 ROS detection 17 3.10 Photodynamic effect triggered by two-photon laser 17 Chapter4 CONCLUSION 19 SCHEME 20 TABLE 21 FIGURE 24 REFERENCE 33 Lists of schemes Scheme 1. Description of the usage of sutent/DOX nanoparticles 20 Scheme 2. Illustration of sutent/DOX nanoparticles 20 Lists of Tables Table 1. Characteristics of drug-loaded NPs 21 Table 2. Combination index (CI) of free drugs combination 22 Table 3. Combination index (CI) of PDT combined chemotherapy 22 Table 4. IC50 of DOX and drug-loaded NPs 23 Lists of Figures Figure 1. TEM images of sutent/Dox NPs 24 Figure 2. Size distribution 24 Figure 3. Stability test of sutent/DOX nanoparticles 25 Figure 4. Absorption spectra 26 Figure 5. DOX IC50 of MCF-7 and MCF7/ADR 27 Figure 6. Cellular uptake of MCF-7/ADR cells 28 Figure 7. ROS detection of MCF-7/ADR cells 29 Figure 8. Cytotoxicity of blank mPEG-PCL NPs 30 Figure 9. Cell viability of chemotherapy, PDT, and PDT combine chemotherapy. 31 Figure 10. Fluorescence image of MCF-7 cells 32 | |
| dc.language.iso | en | |
| dc.subject | 抗藥性乳癌細胞 | zh_TW |
| dc.subject | 光動力治療 | zh_TW |
| dc.subject | 雙光子雷射 | zh_TW |
| dc.subject | photodyphotodynamic effect | en |
| dc.subject | combination therapy | en |
| dc.subject | sutent | en |
| dc.subject | drug-resistant breast cancer | en |
| dc.title | 奈米藥物載體同時包覆Sunitinib 及Doxorubicin 結合光動力治療與化療於抗藥性癌症的應用 | zh_TW |
| dc.title | Co-encapsulation of Sunitinib and Doxorubicin to Enhance Drug Resistance Cancer Treatment via Photodynamic therapy/Chemotherapy | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 楊台鴻(Tai-Horng Young),林文澧(Win-Li Lin),駱俊良(Chun-Liang Lo) | |
| dc.subject.keyword | 光動力治療,抗藥性乳癌細胞,雙光子雷射, | zh_TW |
| dc.subject.keyword | photodyphotodynamic effect,combination therapy,sutent,drug-resistant breast cancer, | en |
| dc.relation.page | 36 | |
| dc.identifier.doi | 10.6342/NTU201802495 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-08-06 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
| 顯示於系所單位： | 醫學工程學研究所 | |
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