請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/68273完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 謝銘鈞 | |
| dc.contributor.author | Ming-Hsien Tsai | en |
| dc.contributor.author | 蔡銘賢 | zh_TW |
| dc.date.accessioned | 2021-06-17T02:16:19Z | - |
| dc.date.available | 2021-01-04 | |
| dc.date.copyright | 2018-01-04 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-10-03 | |
| dc.identifier.citation | Part I:
Ashokkumar, B., Mohammed, Z. M., Vaziri, N. D., & Said, H. M. (2007). Effect of folate oversupplementation on folate uptake by human intestinal and renal epithelial cells. The American Journal of Clinical Nutrition, 86(1), 159-166. Bala, V., Rao, S., Boyd, B. J., & Prestidge, C. A. (2013). Prodrug and nanomedicine approaches for the delivery of the camptothecin analogue SN38. J Control Release, 172(1), 48-61. doi:10.1016/j.jconrel.2013.07.022 Chen, Y.-I., Peng, C.-L., Lee, P.-C., Tsai, M.-H., Lin, C.-Y., Shih, Y.-H., . . . Shieh, M.-J. (2015). Traceable Self-Assembly of Laser-Triggered Cyanine-Based Micelle for Synergistic Therapeutic Effect. Advanced Healthcare Materials, 4(6), 892-902. doi:10.1002/adhm.201400729 Cuong, N.-V., Li, Y.-L., & Hsieh, M.-F. (2012). Targeted delivery of doxorubicin to human breast cancers by folate-decorated star-shaped PEG-PCL micelle. Journal of Materials Chemistry, 22(3), 1006-1020. doi:10.1039/C1JM13588K Ding, J., Zhuang, X., Xiao, C., Cheng, Y., Zhao, L., He, C., . . . Chen, X. (2011). Preparation of photo-cross-linked pH-responsive polypeptide nanogels as potential carriers for controlled drug delivery. Journal of Materials Chemistry, 21(30), 11383-11391. doi:10.1039/C1JM10391A Douillard, J. Y., Cunningham, D., Roth, A. D., Navarro, M., James, R. D., Karasek, P., . . . Rougier, P. (2000). Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. The Lancet, 355(9209), 1041-1047. doi:10.1016/s0140-6736(00)02034-1 Estrella, V., Chen, T., Lloyd, M., Wojtkowiak, J., Cornnell, H. H., Ibrahim-Hashim, A., . . . Gillies, R. J. (2013). Acidity Generated by the Tumor Microenvironment Drives Local Invasion. Cancer Research, 73(5), 1524-1535. doi:10.1158/0008-5472.can-12-2796 Gao, X., Zheng, F., Guo, G., Liu, X., Fan, R., Qian, Z.-y., . . . Wei, Y.-q. (2013). Improving the anti-colon cancer activity of curcumin with biodegradable nano-micelles. Journal of Materials Chemistry B, 1(42), 5778-5790. doi:10.1039/C3TB21091J Ge, Z., & Liu, S. (2013). Functional block copolymer assemblies responsive to tumor and intracellular microenvironments for site-specific drug delivery and enhanced imaging performance. Chemical Society Reviews, 42(17), 7289-7325. doi:10.1039/C3CS60048C Gou, M., Men, K., Shi, H., Xiang, M., Zhang, J., Song, J., . . . Qian, Z. (2011). Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo. Nanoscale, 3(4), 1558-1567. doi:10.1039/C0NR00758G Han, Y., Li, J., Zan, M., Luo, S., Ge, Z., & Liu, S. (2014). Redox-responsive core cross-linked micelles based on cypate and cisplatin prodrugs-conjugated block copolymers for synergistic photothermal-chemotherapy of cancer. Polymer Chemistry, 5(11), 3707-3718. doi:10.1039/C4PY00064A Heldin, C.-H., Rubin, K., Pietras, K., & Ostman, A. (2004). High interstitial fluid pressure - an obstacle in cancer therapy. Nat Rev Cancer, 4(10), 806-813. Huo, M., Yuan, J., Tao, L., & Wei, Y. (2014). Redox-responsive polymers for drug delivery: from molecular design to applications. Polymer Chemistry, 5(5), 1519-1528. doi:10.1039/C3PY01192E Joralemon, M. J., McRae, S., & Emrick, T. (2010). PEGylated polymers for medicine: from conjugation to self-assembled systems. Chemical Communications, 46(9), 1377-1393. doi:10.1039/B920570P Jung, B., Jeong, Y.-C., Min, J.-H., Kim, J.-E., Song, Y.-J., Park, J.-K., . . . Kim, J.-D. (2012). Tumor-binding prodrug micelles of polymer-drug conjugates for anticancer therapy in HeLa cells. Journal of Materials Chemistry, 22(18), 9385-9394. doi:10.1039/C2JM30534H Kawato, Y., Aonuma, M., Hirota, Y., Kuga, H., & Sato, K. (1991). Intracellular Roles of SN-38, a Metabolite of the Camptothecin Derivative CPT-11, in the Antitumor Effect of CPT-11. Cancer Research, 51(16), 4187-4191. Khatik, R., Dwivedi, P., Junnuthula, V. R., Sharma, K., Chuttani, K., Mishra, A. K., & Dwivedi, A. K. (2015). Potential in vitro and in vivo colon specific anticancer activity in a HCT-116 xenograft nude mice model: targeted delivery using enteric coated folate modified nanoparticles. RSC Advances, 5(21), 16507-16520. doi:10.1039/C4RA15114C Lai, T. C., Cho, H., & Kwon, G. S. (2014). Reversibly core cross-linked polymeric micelles with pH- and reduction-sensitivities: effects of cross-linking degree on particle stability, drug release kinetics, and anti-tumor efficacy. Polymer Chemistry, 5(5), 1650-1661. doi:10.1039/C3PY01112G Li, M., Tang, Z., Zhang, Y., Lv, S., Yu, H., Zhang, D., . . . Chen, X. (2014). LHRH-peptide conjugated dextran nanoparticles for targeted delivery of cisplatin to breast cancer. Journal of Materials Chemistry B, 2(22), 3490-3499. doi:10.1039/C4TB00077C Liu, B., Zhang, X., Chen, Y., Yao, Z., Yang, Z., Gao, D., . . . Jiang, Z. (2015). Enzymatic synthesis of poly([small omega]-pentadecalactone-co-butylene-co-3,3[prime or minute]-dithiodipropionate) copolyesters and self-assembly of the PEGylated copolymer micelles as redox-responsive nanocarriers for doxorubicin delivery. Polymer Chemistry, 6(11), 1997-2010. doi:10.1039/C4PY01321B Liu, Y., Chang, Y., Yang, C., Sang, Z., Yang, T., Ang, W., . . . Luo, Y. (2014). Biodegradable nanoassemblies of piperlongumine display enhanced anti-angiogenesis and anti-tumor activities. Nanoscale, 6(8), 4325-4337. doi:10.1039/C3NR06599E Mason, J. B., Shoda, R., Haskell, M., Selhub, J., & Rosenberg, I. H. (1990). Carrier affinity as a mechanism for the pH-dependence of folate transport in the small intestine. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1024(2), 331-335. Oh, K. T., Yin, H., Lee, E. S., & Bae, Y. H. (2007). Polymeric nanovehicles for anticancer drugs with triggering release mechanisms. Journal of Materials Chemistry, 17(38), 3987-4001. doi:10.1039/B707142F Peng, C.-L., Shih, Y.-H., Lee, P.-C., Hsieh, T. M.-H., Luo, T.-Y., & Shieh, M.-J. (2011). Multimodal Image-Guided Photothermal Therapy Mediated by 188Re-Labeled Micelles Containing a Cyanine-Type Photosensitizer. ACS Nano, 5(7), 5594-5607. doi:10.1021/nn201100m Peng, C. L., Shieh, M. J., Tsai, M. H., Chang, C. C., & Lai, P. S. (2008). Self-assembled star-shaped chlorin-core poly(epsilon-caprolactone)-poly(ethylene glycol) diblock copolymer micelles for dual chemo-photodynamic therapies. Biomaterials, 29(26), 3599-3608. doi:10.1016/j.biomaterials.2008.05.018 Peng, C. L., Tsai, H. M., Yang, S. J., Luo, T. Y., Lin, C. F., Lin, W. J., & Shieh, M. J. (2011). Development of thermosensitive poly(n-isopropylacrylamide-co-((2-dimethylamino) ethyl methacrylate))-based nanoparticles for controlled drug release. Nanotechnology, 22(26), 265608. doi:10.1088/0957-4484/22/26/265608 Peng, C. L., Yang, L. Y., Luo, T. Y., Lai, P. S., Yang, S. J., Lin, W. J., & Shieh, M. J. (2010). Development of pH sensitive 2-(diisopropylamino)ethyl methacrylate based nanoparticles for photodynamic therapy. Nanotechnology, 21(15), 155103. doi:10.1088/0957-4484/21/15/155103 Sinn Aw, M., Kurian, M., & Losic, D. (2014). Non-eroding drug-releasing implants with ordered nanoporous and nanotubular structures: concepts for controlling drug release. Biomaterials Science, 2(1), 10-34. doi:10.1039/C3BM60196J Subramanian, V. S., Reidling, J. C., & Said, H. M. (2008). Differentiation-dependent regulation of the intestinal folate uptake process: studies with Caco-2 cells and native mouse intestine (Vol. 295). Talelli, M., Oliveira, S., Rijcken, C. J. F., Pieters, E. H. E., Etrych, T., Ulbrich, K., . . . Lammers, T. (2013). Intrinsically active nanobody-modified polymeric micelles for tumor-targeted combination therapy. Biomaterials, 34(4), 1255-1260. Vaupel, P., Kallinowski, F., & Okunieff, P. (1989). Blood Flow, Oxygen and Nutrient Supply, and Metabolic Microenvironment of Human Tumors: A Review. Cancer Research, 49(23), 6449-6465. Weitman, S. D., Lark, R. H., Coney, L. R., Fort, D. W., Frasca, V., Zurawski, V. R., & Kamen, B. A. (1992). Distribution of the Folate Receptor GP38 in Normal and Malignant Cell Lines and Tissues. Cancer Research, 52(12), 3396-3401. Xing, Q., Li, N., Jiao, Y., Chen, D., Xu, J., Xu, Q., & Lu, J. (2015). Near-infrared light-controlled drug release and cancer therapy with polymer-caged upconversion nanoparticles. RSC Advances, 5(7), 5269-5276. doi:10.1039/C4RA12678E Xu, S., Olenyuk, B. Z., Okamoto, C. T., & Hamm-Alvarez, S. F. (2013). Targeting receptor-mediated endocytotic pathways with nanoparticles: rationale and advances. Adv Drug Deliv Rev, 65(1), 121-138. doi:10.1016/j.addr.2012.09.041 Yue, J., Liu, S., Xie, Z., Xing, Y., & Jing, X. (2013). Size-dependent biodistribution and antitumor efficacy of polymer micelle drug delivery systems. Journal of Materials Chemistry B, 1(34), 4273-4280. doi:10.1039/C3TB20296H Yue, T., & Zhang, X. (2011). Molecular understanding of receptor-mediated membrane responses to ligand-coated nanoparticles. Soft Matter, 7(19), 9104-9112. doi:10.1039/C1SM05398A Part II: Brooks, P. C., Clark, R. A., & Cheresh, D. A. (1994). Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science, 264(5158), 569-571. Chen, Y.-I., Peng, C.-L., Lee, P.-C., Tsai, M.-H., Lin, C.-Y., Shih, Y.-H., . . . Shieh, M.-J. (2015). Traceable Self-Assembly of Laser-Triggered Cyanine-Based Micelle for Synergistic Therapeutic Effect. Advanced Healthcare Materials, 4(6), 892-902. doi:10.1002/adhm.201400729 Corbo, C., Molinaro, R., Tabatabaei, M., Farokhzad, O. C., & Mahmoudi, M. (2017). Personalized protein corona on nanoparticles and its clinical implications. Biomaterials Science, 5(3), 378-387. doi:10.1039/C6BM00921B Guo, X., Li, D., Yang, G., Shi, C., Tang, Z., Wang, J., & Zhou, S. (2014). Thermo-triggered drug release from actively targeting polymer micelles. ACS Appl Mater Interfaces, 6(11), 8549-8559. doi:10.1021/am501422r Petersen, M. A., Hillmyer, M. A., & Kokkoli, E. (2013). Bioresorbable polymersomes for targeted delivery of cisplatin. Bioconjug Chem, 24(4), 533-543. doi:10.1021/bc3003259 Song, C. W. (1984). Effect of local hyperthermia on blood flow and microenvironment: a review. Cancer Res, 44(10 Suppl), 4721s-4730s. Bottini, M., Rosato, N., & Bottini, N. (2011). PEG-Modified Carbon Nanotubes in Biomedicine: Current Status and Challenges Ahead. Biomacromolecules, 12(10), 3381-3393. doi:10.1021/bm201020h Chauhan, V. P., Stylianopoulos, T., Martin, J. D., Popovic, Z., Chen, O., Kamoun, W. S., . . . Jain, R. K. (2012). Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner. Nat Nano, 7(6), 383-388. Chen, J., Wang, D., Xi, J., Au, L., Siekkinen, A., Warsen, A., . . . Li, X. (2007). Immuno Gold Nanocages with Tailored Optical Properties for Targeted Photothermal Destruction of Cancer Cells. Nano Letters, 7(5), 1318-1322. doi:10.1021/nl070345g Chen, Q., Wen, J., Li, H., Xu, Y., Liu, F., & Sun, S. (2016). Recent advances in different modal imaging-guided photothermal therapy. Biomaterials, 106, 144-166. Chen, Y.-I., Peng, C.-L., Lee, P.-C., Tsai, M.-H., Lin, C.-Y., Shih, Y.-H., . . . Shieh, M.-J. (2015). Traceable Self-Assembly of Laser-Triggered Cyanine-Based Micelle for Synergistic Therapeutic Effect. Advanced Healthcare Materials, 4(6), 892-902. doi:10.1002/adhm.201400729 Chou, S.-T., Leng, Q., Scaria, P., Kahn, J. D., Tricoli, L. J., Woodle, M., & Mixson, A. J. (2013). Surface-Modified HK:siRNA Nanoplexes with Enhanced Pharmacokinetics and Tumor Growth Inhibition. Biomacromolecules, 14(3), 752-760. doi:10.1021/bm3018356 Danhier, F., Breton, A. L., & Préat, V. (2012). RGD-Based Strategies To Target Alpha(v) Beta(3) Integrin in Cancer Therapy and Diagnosis. Molecular Pharmaceutics, 9(11), 2961-2973. doi:10.1021/mp3002733 Dong, K., Liu, Z., Li, Z., Ren, J., & Qu, X. (2013). Hydrophobic Anticancer Drug Delivery by a 980 nm Laser-Driven Photothermal Vehicle for Efficient Synergistic Therapy of Cancer Cells In Vivo. Advanced Materials, 25(32), 4452-4458. doi:10.1002/adma.201301232 Etheridge, M. L., Campbell, S. A., Erdman, A. G., Haynes, C. L., Wolf, S. M., & McCullough, J. (2013). The big picture on nanomedicine: the state of investigational and approved nanomedicine products. Nanomedicine, 9(1), 1-14. doi:10.1016/j.nano.2012.05.013 Fahrni, C. J., Yang, L., & VanDerveer, D. G. (2003). Tuning the photoinduced electron-transfer thermodynamics in 1,3,5-triaryl-2-pyrazoline fluorophores: X-ray structures, photophysical characterization, computational analysis, and in vivo evaluation. J Am Chem Soc, 125(13), 3799-3812. doi:10.1021/ja028266o Fang, J., Nakamura, H., & Maeda, H. (2011). The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev, 63(3), 136-151. Grasl-Kraupp, B., Ruttkay-Nedecky, B., Koudelka, H., Bukowska, K., Bursch, W., & Schulte-Hermann, R. (1995). In situ detection of fragmented DNA (tunel assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: A cautionary note. Hepatology, 21(5), 1465-1468. Haag, R. (2004). Supramolecular Drug-Delivery Systems Based on Polymeric Core–Shell Architectures. Angewandte Chemie International Edition, 43(3), 278-282. doi:10.1002/anie.200301694 Ju, E., Li, Z., Liu, Z., Ren, J., & Qu, X. (2014). Near-Infrared Light-Triggered Drug-Delivery Vehicle for Mitochondria-Targeted Chemo-Photothermal Therapy. ACS Applied Materials & Interfaces, 6(6), 4364-4370. doi:10.1021/am5000883 Kim, S. H., Lee, J. E., Sharker, S. M., Jeong, J. H., In, I., & Park, S. Y. (2015). In Vitro and In Vivo Tumor Targeted Photothermal Cancer Therapy Using Functionalized Graphene Nanoparticles. Biomacromolecules, 16(11), 3519-3529. doi:10.1021/acs.biomac.5b00944 Li, Z., Huang, P., Zhang, X., Lin, J., Yang, S., Liu, B., . . . Cui, D. (2010). RGD-Conjugated Dendrimer-Modified Gold Nanorods for in Vivo Tumor Targeting and Photothermal Therapy. Molecular Pharmaceutics, 7(1), 94-104. doi:10.1021/mp9001415 Mahabeleshwar, G. H., Feng, W., Reddy, K., Plow, E. F., & Byzova, T. V. (2007). Mechanisms of Integrin–Vascular Endothelial Growth Factor Receptor Cross-Activation in Angiogenesis. Circulation Research, 101(6), 570-580. doi:10.1161/circresaha.107.155655 Mathijssen, R. H., van Alphen, R. J., Verweij, J., Loos, W. J., Nooter, K., Stoter, G., & Sparreboom, A. (2001). Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin Cancer Res, 7(8), 2182-2194. Matsumura, Y. (2011). Preclinical and clinical studies of NK012, an SN-38-incorporating polymeric micelles, which is designed based on EPR effect. Adv Drug Deliv Rev, 63(3), 184-192. Matsumura, Y., & Maeda, H. (1986). A New Concept for Macromolecular Therapeutics in Cancer Chemotherapy: Mechanism of Tumoritropic Accumulation of Proteins and the Antitumor Agent Smancs. Cancer Research, 46(12 Part 1), 6387-6392. Mauro, N., Scialabba, C., Cavallaro, G., Licciardi, M., & Giammona, G. (2015). Biotin-Containing Reduced Graphene Oxide-Based Nanosystem as a Multieffect Anticancer Agent: Combining Hyperthermia with Targeted Chemotherapy. Biomacromolecules, 16(9), 2766-2775. doi:10.1021/acs.biomac.5b00705 Ning, S.-T., Lee, S.-Y., Wei, M.-F., Peng, C.-L., Lin, S. Y.-F., Tsai, M.-H., . . . Shieh, M.-J. (2016). Targeting Colorectal Cancer Stem-Like Cells with Anti-CD133 Antibody-Conjugated SN-38 Nanoparticles. ACS Applied Materials & Interfaces, 8(28), 17793-17804. doi:10.1021/acsami.6b04403 Padayachee, E. R., Arowolo, A., & Whiteley, C. G. (2014). Nanomedicine: action of metal nanoparticles on neuronal nitric oxide synthase-fluorimetric analysis on the mechanism for fibrillogenesis. Neurochem Res, 39(1), 194-201. doi:10.1007/s11064-013-1206-x Peng, C.-L., Shih, Y.-H., Lee, P.-C., Hsieh, T. M.-H., Luo, T.-Y., & Shieh, M.-J. (2011). Multimodal Image-Guided Photothermal Therapy Mediated by 188Re-Labeled Micelles Containing a Cyanine-Type Photosensitizer. ACS Nano, 5(7), 5594-5607. doi:10.1021/nn201100m Peng, C. L., Lai, P. S., Lin, F. H., Yueh-Hsiu Wu, S., & Shieh, M. J. (2009). Dual chemotherapy and photodynamic therapy in an HT-29 human colon cancer xenograft model using SN-38-loaded chlorin-core star block copolymer micelles. Biomaterials, 30(21), 3614-3625. doi:10.1016/j.biomaterials.2009.03.048 Peng, C. L., Shieh, M. J., Tsai, M. H., Chang, C. C., & Lai, P. S. (2008). Self-assembled star-shaped chlorin-core poly(epsilon-caprolactone)-poly(ethylene glycol) diblock copolymer micelles for dual chemo-photodynamic therapies. Biomaterials, 29(26), 3599-3608. doi:10.1016/j.biomaterials.2008.05.018 Seront, E., Marot, L., Coche, E., Gala, J.-L., Sempoux, C., & Humblet, Y. (2010). Successful long-term management of a patient with late-stage metastatic colorectal cancer treated with panitumumab. Cancer Treatment Reviews, 36, S11-S14. doi:10.1016/S0305-7372(10)70002-5 Soldi, R., Mitola, S., Strasly, M., Defilippi, P., Tarone, G., & Bussolino, F. (1999). Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. The EMBO Journal, 18(4), 882-892. doi:10.1093/emboj/18.4.882 Song, F., Peng, X., Lu, E., Wang, Y., Zhou, W., & Fan, J. (2005). Tuning the photoinduced electron transfer in near-infrared heptamethine cyanine dyes. Tetrahedron Letters, 46(28), 4817-4820. Sun, L., Ma, X., Dong, C.-M., Zhu, B., & Zhu, X. (2012). NIR-Responsive and Lectin-Binding Doxorubicin-Loaded Nanomedicine from Janus-Type Dendritic PAMAM Amphiphiles. Biomacromolecules, 13(11), 3581-3591. doi:10.1021/bm3010325 Tanford, C. (1974). Theory of micelle formation in aqueous solutions. The Journal of Physical Chemistry, 78(24), 2469-2479. doi:10.1021/j100617a012 Tsai, M.-H., Peng, C.-L., Yao, C.-J., & Shieh, M.-J. (2015). Enhanced efficacy of chemotherapeutic drugs against colorectal cancer using ligand-decorated self-breakable agents. RSC Advances, 5(112), 92361-92370. doi:10.1039/C5RA16175D van Dongen, M. A., Dougherty, C. A., & Banaszak Holl, M. M. (2014). Multivalent Polymers for Drug Delivery and Imaging: The Challenges of Conjugation. Biomacromolecules, 15(9), 3215-3234. doi:10.1021/bm500921q Wang, H., Han, R.-l., Yang, L.-m., Shi, J.-h., Liu, Z.-j., Hu, Y., . . . Gan, Y. (2016). Design and Synthesis of Core–Shell–Shell Upconversion Nanoparticles for NIR-Induced Drug Release, Photodynamic Therapy, and Cell Imaging. ACS Applied Materials & Interfaces, 8(7), 4416-4423. doi:10.1021/acsami.5b11197 Wu, L., Fang, S., Shi, S., Deng, J., Liu, B., & Cai, L. (2013). Hybrid Polypeptide Micelles Loading Indocyanine Green for Tumor Imaging and Photothermal Effect Study. Biomacromolecules, 14(9), 3027-3033. doi:10.1021/bm400839b Yuan, A., Qiu, X., Tang, X., Liu, W., Wu, J., & Hu, Y. (2015). Self-assembled PEG-IR-780-C13 micelle as a targeting, safe and highly-effective photothermal agent for in vivo imaging and cancer therapy. Biomaterials, 51, 184-193. doi:10.1016/j.biomaterials.2015.01.069 Yuan, A., Qiu, X., Tang, X., Liu, W., Wu, J., & Hu, Y. (2015). Self-assembled PEG-IR-780-C13 micelle as a targeting, safe and highly-effective photothermal agent for in vivo imaging and cancer therapy. Biomaterials, 51, 184-193. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/68273 | - |
| dc.description.abstract | Part I:
大腸癌的治療發展迄今，已經有許多專門提升化療藥物療效的奈米載體被研製出來，這些奈米載體不但能提升化療藥物於腫瘤的累積量，若被設計賦予其他特殊功能，則能夠更加提升化療藥物的療效；常賦予的功能中，標靶功能可增加腫瘤細胞的吞噬量，而藥物釋放功能則可有效地促使藥物從載體內釋放，提高藥物於細胞內的作用機率。有了以上文獻結果的借鏡，我們團隊針對大腸癌治療的研究，設計一新的多功能奈米載體，使其具有標靶作用與藥物釋放作用；此奈米載體富有雙硫鍵，能包覆大腸癌化療藥物－SN38，期望將來能成為臨床用大腸癌的化療候選藥。於此研究中，三種不同的奈米載體藥物被設計出來互相比較與評估，其分別為可分解型、不可分解型與葉酸標靶可分解型微胞；經評估後，葉酸標靶可分解型的奈米微胞可望成為一有效大腸癌化療的新劑型 Part II: 癌症研究中，熱療法與化療法並用已證實，用於近紅外線且具有特殊功能治療劑能抑制腫瘤生長，故此研究採用熱化療法以期能治癒大腸癌，利用尋找一新的策略，促使腫瘤能夠累積大量的化療藥物且在光熱療程中產生高溫，藉此得到最佳的療效。因此，我們設計一簡單且多功能近紅外線劑型，此劑型由近紅外線染劑、聚乙二醇、環狀胜肽－cRGD所組成，並搭載抗大腸癌化療藥物－SN38。劑型的每個組成皆有它特殊功能，都能夠提升熱化療法的療效。而從此篇研究結果顯示，這個新劑型所賦予的進紅外光顯影能力、光熱功能、高滲透長時間腫瘤滯留現象、躲避網狀內皮系統功能與新生血管標靶特性，能強化熱化療法對於大腸癌的效果。期望這新劑型有助於將來開發新的治療法用於大腸癌。 | zh_TW |
| dc.description.abstract | Part I:
Several types of nano-sized anti-cancer agents that could increase the accumulation of drugs in the tumor site have been created and developed for enhancing efficacy of chemotherapeutic drugs in colon cancer treatment. In addition, to achieve the optimal cancer chemotherapeutic efficacy, nano-sized agents with specific functions were designed to efficiently kill cancer cells. The ideal nano-sized agent must be able to successfully release the drug and result in an increased cellular uptake of the chemotherapeutic drug. Our research team focused on two important functions, drug release and targeting functions, thus targeting functional micelles which were designed to possess disulfide bonds and entrapped much chemotherapeutic drug, 7-ethyl-10-hydroxy-camptothecin (SN38), which was created as a powerful candidate for an ideal anti-cancer drug for colon cancer treatment. In particular, Self-Breakable SN38-loaded micelles (SN/38 micelles), Non-Breakable micelles SN38-loaded (NB/38 micelles) and Folate-decorated Self-Breakable SN38-loaded micelles (FSB/38 micelles) were prepared and tested to the designed agents. The results showed that the folate-decorated functional micelles with disulfide bonds could be an effective chemotherapeutic agent for colon cancer treatment. Part II: Cancer researches regarding near-infrared(NIR) agents for chemothermal therapy(CTT) have shown that agents with specific functions are able to inhibit tumor growth. The aim of current study was to optimize CTT efficacy for treatment of colorectal cancer(CRC) by exploring strategies which can localize high temperature within tumors and maximize chemotherapeutic drug uptake. We designed a new and simple multifunctional NIR nanoagent composed of the NIR cyanine dye, polyethylene glycol, and a cyclic arginine-glycine-aspartic acid peptide and loaded with the anti-CRC chemotherapeutic agent, 7-ethyl-10-hydroxy-camptothecin(SN38). Each component of this nanoagent exhibited its specific functions that help boost CTT efficacy. The results showed that this nanoagent greatly strengthen the efficacy of SN38 and CTT againstCRC due to its NIR imaging ability, photothermal, enhanced permeability and retention(EPR) effect, reticuloendothelial system avoidance, and angiogenic blood vessel-targeting properties. This NIR nanoagent will help facilitate development of new strategies for treating CRC. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T02:16:19Z (GMT). No. of bitstreams: 1 ntu-106-D00548005-1.pdf: 3735123 bytes, checksum: a5f824badaacba9b2f4198c95c40f807 (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
目錄 ii Acknowledgement iv PART I: Enhanced efficacy of chemotherapeutic drugs against colorectal cancer using ligand-decorated self-breakable agents 1 中文摘要 2 Abstract 3 List of Schemes 4 List of Graphics 5 List of Tables 7 Introduction 8 Materials and Methods 13 Results and Discussion 22 Reference 54 PART II: Photothermal, Targeting, Theranostic Near-infrared Nanoagent with SN38 against Colorectal Cancer for Chemo-thermal Therapy 62 中文摘要 63 Abstract 64 List of Scheme 65 List of Graphics 66 List of Tables 68 Introduction 69 Materials and Methods 74 Results and Discussion 86 Conclusion 128 Reference 129 Part I: List of Schemes Scheme 1. Illustration of the efficient cellular uptake of targeting self-breakable drug in acidic tumor microenvironment and redox-responsive drug release in intracellular environment 12 Scheme 2. Structure of a targeting self-breakable SN38-loaded micelle 23 List of Graphics Figure 1. 1H-NMR spectra of copolymer, mPEG-S-S-PCL 23 Figure 2. FT-IR spectra of folate-PEG-PCL and folate 25 Figure 3. GPC analysis of mPEG-S-S-PCL, mPEG, and SB/38 micelle＋DTT 25 Figure 4. TEM images of FSB micelle, FSB/38 micelle, and FSB/38 micelle with DTT 28 Figure 5. Size distribution of FSB/38 micelle 28 Figure 6. Critical micelle concentration of SB micelle, NB micelle, and FSB micelle 30 Figure 7. Stabilities of SB/38 micelle and NB/38 micelle incubated with or without DTT for 24 h 33 Figure 8. SN38 release profile of SB/38 micelle and NB/38 micelle in the presence or absence of DTT. 35 Figure 9. Long-term stability of FSB/38 micelle. Stability of FSB/38 micelle in the environments at pH 6.7 or pH 7.4. 37 Figure 10. Cytotoxicities of SB micelle and NB micelle and LD50 of FSB/38 micelle, SB/38 micelle, NB/38 micelle, and SN38 40 Figure 11. Cytotoxicity of FSB/38 micelle in media with different pH values. Cell viability of SN38, NB/38 micelle, SB/38 micelle, and FSB/38 micelle. 40 Figure 12. Cellular binding of FSB/38 micelle, SB/38 micelle and FSB/38 micelle incubated with folate. Cellular uptake of FSB/38 micelle, SB/38 micelle and FSB/38 micelle incubated with folate 44 Figure 13. Cellular binding. Confocal images of FITC-SB/38 micelle, FITC-FSB/38 micelle, and FITC-FSB/38 micelle incubated with folate. 45 Figure 14. Cellular uptake. Confocal images of FITC-SB/38 micelle, FITC-FSB/38 micelle, and FITC-FSB/38 micelle incubated with folate 46 Figure 15. Cellular uptake. Confocal images of FITC-FSB/38 micelle at different pH values 47 Figure 16. Body weight change of mice. 50 Figure 17. In vivo efficacy of FSB/38 micelle, SB/38 micelle), FSB/38 micelle, and CPT-11. 50 Figure 18. Photographs of tumor-bearing nude mice on day 30 51 List of Tables Table 1. Molecular characteristics of mPEG-S-S-PCL, mPEG-5000, and SB/38 micelles incubated with DTT. 24 Table 2. Characteristics of NB micelle, NB/38 micelle, SB micelle, SB/38 micelle, FSB micelle and FSB/38 micelle 29 Table 3. Number of FSB/38 micelles per milliliter, copolymers per FSB/38 micelle, and SN38s per FSB/38 micelle. 30 Part II: List of Scheme Scheme 3. Efficient accumulation of the designed drug-loaded NIR nanoagent in the tumor site after intravenous injection and administration of PTT to enhance efficacy of CTT. 73 List of Graphics Figure 19. (A) Synthesis of IR780-mPEG and IR780-PEG-cRGD and their self-assembly into the SN38-loaded multifunctional NIR nanoagent (B) Size distribution analysis (C) Absorption spectra (D) FL spectra (E) In vitro photothermal effect (F) DLS size and PdI of IRNANOSN38 at 25°C, 37°C, 45°C, 50°C, and 60°C. (G) SN38 release profile. 93 Figure 20. 1HNMR spectrum of mPEG-IR780. 94 Figure 21. 1HNMR spectrum of cRGD-PEG-IR780. 95 Figure 22. GPC analysis of mPEG-5000, mPEG-IR780, and cRGD-PEG-IR780. 96 Figure 23. TEM images of IRNANO, cRGDIRNANO, IRNANOSN38, and cRGDIRNANOSN38 99 Figure 24. Critical micelle concentration of IRNANO and cRGDIRNANO 99 Figure 25. Absorption spectra of SN38, IR780, IRNANO, and IRNANOSN38 100 Figure 26. In vitro photothermal effect of IRNANO 100 Figure 27. TEM images of IRNANOSN38 at 25°C and after treatment with NIR light 101 Figure 28. In vitro cytotoxicity of IRNANO and cRGDIRNANO 106 Figure 29. In vitro cytotoxicity of chemo, PTT, and CTT 107 Figure 30. Dead and dying cells determined by ethidium homodimer-1 assay 109 Figure 31. PK analysis of SN38, IRNANOSN38, and cRGDIRNANOSN38 112 Figure 32. In vivo NIR imaging and tumor accumulation 116 Figure 33. In vivo photothermal effect. 119 Figure 34. Antitumor efficacy.. 124 Figure 35. Representative photos of tumor-bearing mice on days 1, 2, 3, 9, 15, and 21. 126 Figure 36. Relative body weight of tumor-bearing mice treated with saline, the designed chemo, PTT, or CTT and H&E sections from normal organs of mice on day 21 127 List of Tables Table 4. Molecular characteristics of mPEG-5000, mPEG-IR780, and cRGD-PEG-IR780. 97 Table 5. Characteristics of IRNANO, IRNANOSN38, cRGDIRNANO, and cRGDIRNANOSN38. 98 Table 6. IC50 values of free SN38, IRNANOSN38, and cRGDIRNANOSN38 (in equivalent μg/mL SN38) on colorectal cancer cell lines. 108 Table 7. In vitro synergistic effect of chemo and PTT. 110 Table 8. Pharmacokinetic parameters 113 | |
| dc.language.iso | en | |
| dc.subject | SN38 | zh_TW |
| dc.subject | 奈米 | zh_TW |
| dc.subject | 奈米 Part II: 大腸癌 | zh_TW |
| dc.subject | 葉酸 | zh_TW |
| dc.subject | 雙硫鍵 | zh_TW |
| dc.subject | 微胞 | zh_TW |
| dc.subject | 光熱療法 | zh_TW |
| dc.subject | Part I: 大腸癌 | zh_TW |
| dc.subject | 環狀胜? | zh_TW |
| dc.subject | cyclic RGD | en |
| dc.subject | SN38 | en |
| dc.subject | micelle | en |
| dc.subject | folate | en |
| dc.subject | disulfide bond. Part II: colorectal cancer | en |
| dc.subject | chemothermal therapy | en |
| dc.subject | Part I: Colorectal cancer | en |
| dc.subject | SN38 | en |
| dc.subject | nano | en |
| dc.title | 設計新搭載化療藥物SN38之多功能奈米載體與其抗大腸癌療效評估 | zh_TW |
| dc.title | Efficacy Evaluation of Newly Designed Multifunctional Nanoagents with SN38 against Colorectal Cancer | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 駱俊良,楊禎明,張富雄,胡宇方,宋信文 | |
| dc.subject.keyword | Part I: 大腸癌,微胞,雙硫鍵,葉酸,奈米 Part II: 大腸癌,光熱療法,環狀胜?,SN38,奈米, | zh_TW |
| dc.subject.keyword | Part I: Colorectal cancer,SN38,micelle,folate,disulfide bond. Part II: colorectal cancer,chemothermal therapy,cyclic RGD,SN38,nano, | en |
| dc.relation.page | 137 | |
| dc.identifier.doi | 10.6342/NTU201704247 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-10-03 | |
| 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 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-106-1.pdf 未授權公開取用 | 3.65 MB | Adobe PDF |
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。