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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 謝銘鈞(Ming-Jium Shieh) | |
dc.contributor.author | Chun-Yen Lin | en |
dc.contributor.author | 林君彥 | zh_TW |
dc.date.accessioned | 2021-06-08T02:40:15Z | - |
dc.date.copyright | 2018-05-17 | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018-05-04 | |
dc.identifier.citation | (1) Kong, F. Y.; Zhang, J. W.; Li, R. F.; Wang, Z. X.; Wang, W. J.; Wang, W. Unique Roles of Gold Nanoparticles in Drug Delivery, Targeting and Imaging Applications. Molecules 2017, 22 (9).
(2) Han, Y.; Shchukin, D.; Yang, J.; Simon, C. R.; Fuchs, H.; Mohwald, H. Biocompatible protein nanocontainers for controlled drugs release. ACS Nano 2010, 4 (5), 2838-2844. (3) Elzoghby, A. O.; Samy, W. M.; Elgindy, N. A. Protein-based nanocarriers as promising drug and gene delivery systems. J Control Release 2012, 161 (1), 38-49. (4) Miele, E.; Spinelli, G. P.; Tomao, F.; Tomao, S. Albumin-bound formulation of paclitaxel (Abraxane ABI-007) in the treatment of breast cancer. Int J Nanomedicine 2009, 4, 99-105. (5) Wani, M. C.; Taylor, H. L.; Wall, M. E.; Coggon, P.; McPhail, A. T. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 1971, 93 (9), 2325-2327. (6) Gradishar, W. J. Albumin-bound paclitaxel: a next-generation taxane. Expert Opin Pharmacother 2006, 7 (8), 1041-1053. (7) Gianni, L.; Kearns, C. M.; Giani, A.; Capri, G.; Vigano, L.; Lacatelli, A.; Bonadonna, G.; Egorin, M. J. Nonlinear pharmacokinetics and metabolism of paclitaxel and its pharmacokinetic/pharmacodynamic relationships in humans. J Clin Oncol 1995, 13 (1), 180-190. (8) Ewertz, M.; Qvortrup, C.; Eckhoff, L. Chemotherapy-induced peripheral neuropathy in patients treated with taxanes and platinum derivatives. Acta Oncol 2015, 54 (5), 587-591. (9) Rimac, H.; Debeljak, Z.; Bojic, M.; Miller, L. Displacement of Drugs from Human Serum Albumin: From Molecular Interactions to Clinical Significance. Curr Med Chem 2017, 24 (18), 1930-1947. (10) Flenniken, M. L.; Uchida, M.; Liepold, L. O.; Kang, S.; Young, M. J.; Douglas, T. A library of protein cage architectures as nanomaterials. Curr Top Microbiol Immunol 2009, 327, 71-93. (11) Amenabar, I.; Poly, S.; Nuansing, W.; Hubrich, E. H.; Govyadinov, A. A.; Huth, F.; Krutokhvostov, R.; Zhang, L.; Knez, M.; Heberle, J.; Bittner, A. M.; Hillenbrand, R. Structural analysis and mapping of individual protein complexes by infrared nanospectroscopy. Nat Commun 2013, 4, 2890. (12) Chauhan, V. P.; Stylianopoulos, T.; Martin, J. D.; Popovic, Z.; Chen, O.; Kamoun, W. S.; Bawendi, M. G.; Fukumura, D.; Jain, R. K. Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner. Nat Nanotechnol 2012, 7 (6), 383-388. (13) Schoonen, L.; van Hest, J. C. Functionalization of protein-based nanocages for drug delivery applications. Nanoscale 2014, 6 (13), 7124-7141. (14) Mazur, A.; Litt, I.; Shorr, E. Chemical properties of ferritin and their relation to its vasodepressor activity. J Biol Chem 1950, 187 (2), 473-484. (15) Honarmand Ebrahimi, K.; Bill, E.; Hagedoorn, P. L.; Hagen, W. R. The catalytic center of ferritin regulates iron storage via Fe(II)-Fe(III) displacement. Nat Chem Biol 2012, 8 (11), 941-948. (16) Quail, D. F.; Joyce, J. A. Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013, 19 (11), 1423-1437. (17) Estrella, V.; Chen, T.; Lloyd, M.; Wojtkowiak, J.; Cornnell, H. H.; Ibrahim-Hashim, A.; Bailey, K.; Balagurunathan, Y.; Rothberg, J. M.; Sloane, B. F.; Johnson, J.; Gatenby, R. A.; Gillies, R. J. Acidity generated by the tumor microenvironment drives local invasion. Cancer Res 2013, 73 (5), 1524-1535. (18) Lin, C. Y.; Shieh, M. J. Near-Infrared Fluorescent Dye-Decorated Nanocages to Form Grenade-like Nanoparticles with Dual Control Release for Photothermal Theranostics and Chemotherapy. Bioconjug Chem 2018, 29 (4), 1384-1398. (19) Zhen, Z.; Tang, W.; Zhang, W.; Xie, J. Folic acid conjugated ferritins as photosensitizer carriers for photodynamic therapy. Nanoscale 2015, 7 (23), 10330-10333. (20) Lin, C. Y.; Yang, S. J.; Peng, C. L.; Shieh, M. J. Panitumumab-Conjugated and Platinum-Cored pH-Sensitive Apoferritin Nanocages for Colorectal Cancer-Targeted Therapy. ACS Appl Mater Interfaces 2018, 10 (7), 6096-6106. (21) Truffi, M.; Fiandra, L.; Sorrentino, L.; Monieri, M.; Corsi, F.; Mazzucchelli, S. Ferritin nanocages: A biological platform for drug delivery, imaging and theranostics in cancer. Pharmacol Res 2016, 107, 57-65. (22) Yang, Z.; Wang, X.; Diao, H.; Zhang, J.; Li, H.; Sun, H.; Guo, Z. Encapsulation of platinum anticancer drugs by apoferritin. Chem Commun (Camb) 2007, (33), 3453-3455. (23) Geninatti Crich, S.; Bussolati, B.; Tei, L.; Grange, C.; Esposito, G.; Lanzardo, S.; Camussi, G.; Aime, S. Magnetic resonance visualization of tumor angiogenesis by targeting neural cell adhesion molecules with the highly sensitive gadolinium-loaded apoferritin probe. Cancer Res 2006, 66 (18), 9196-9201. (24) Dominguez-Vera, J. M. Iron(III) complexation of Desferrioxamine B encapsulated in apoferritin. J Inorg Biochem 2004, 98 (3), 469-472. (25) Zhen, Z.; Tang, W.; Chen, H.; Lin, X.; Todd, T.; Wang, G.; Cowger, T.; Chen, X.; Xie, J. RGD-modified apoferritin nanoparticles for efficient drug delivery to tumors. ACS Nano 2013, 7 (6), 4830-4837. (26) Zhen, Z.; Tang, W.; Guo, C.; Chen, H.; Lin, X.; Liu, G.; Fei, B.; Chen, X.; Xu, B.; Xie, J. Ferritin nanocages to encapsulate and deliver photosensitizers for efficient photodynamic therapy against cancer. ACS Nano 2013, 7 (8), 6988-6996. (27) Jang, J. S.; Kim, S. J.; Choi, S. J.; Kim, N. H.; Hakim, M.; Rothschild, A.; Kim, I. D. Thin-walled SnO(2) nanotubes functionalized with Pt and Au catalysts via the protein templating route and their selective detection of acetone and hydrogen sulfide molecules. Nanoscale 2015, 7 (39), 16417-16426. (28) Qiu, H.; Dong, X.; Sana, B.; Peng, T.; Paramelle, D.; Chen, P.; Lim, S. Ferritin-templated synthesis and self-assembly of Pt nanoparticles on a monolithic porous graphene network for electrocatalysis in fuel cells. ACS Appl Mater Interfaces 2013, 5 (3), 782-787. (29) Sana, B.; Poh, C. L.; Lim, S. A manganese-ferritin nanocomposite as an ultrasensitive T2 contrast agent. Chem Commun (Camb) 2012, 48 (6), 862-864. (30) Haggar, F. A.; Boushey, R. P. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg 2009, 22 (4), 191-197. (31) Siegel, R. L.; Miller, K. D.; Jemal, A. Cancer Statistics, 2017. CA Cancer J Clin 2017, 67 (1), 7-30. (32) Hu, F.; Wei, F.; Wang, Y.; Wu, B.; Fang, Y.; Xiong, B. EGCG synergizes the therapeutic effect of cisplatin and oxaliplatin through autophagic pathway in human colorectal cancer cells. J Pharmacol Sci 2015, 128 (1), 27-34. (33) Focan, C.; Kreutz, F.; Focan-Henrard, D.; Moeneclaey, N. Chronotherapy with 5-fluorouracil, folinic acid and carboplatin for metastatic colorectal cancer; an interesting therapeutic index in a phase II trial. Eur J Cancer 2000, 36 (3), 341-347. (34) Carethers, J. M. Systemic treatment of advanced colorectal cancer: tailoring therapy to the tumor. Therap Adv Gastroenterol 2008, 1 (1), 33-42. (35) Vanneman, M.; Dranoff, G. Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer 2012, 12 (4), 237-251. (36) Tang, Y.; Lou, J.; Alpaugh, R. K.; Robinson, M. K.; Marks, J. D.; Weiner, L. M. Regulation of antibody-dependent cellular cytotoxicity by IgG intrinsic and apparent affinity for target antigen. J Immunol 2007, 179 (5), 2815-2823. (37) Michaelsen, T. E.; Aase, A.; Norderhaug, L.; Sandlie, I. Antibody dependent cell-mediated cytotoxicity induced by chimeric mouse-human IgG subclasses and IgG3 antibodies with altered hinge region. Mol Immunol 1992, 29 (3), 319-326. (38) Scott, A. M.; Wolchok, J. D.; Old, L. J. Antibody therapy of cancer. Nat Rev Cancer 2012, 12 (4), 278-287. (39) Hansel, T. T.; Kropshofer, H.; Singer, T.; Mitchell, J. A.; George, A. J. The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov 2010, 9 (4), 325-338. (40) Yaqub, F. Nivolumab for squamous-cell non-small-cell lung cancer. Lancet Oncol 2015, 16 (7), e319. (41) Robert, C.; Long, G. V.; Brady, B.; Dutriaux, C.; Maio, M.; Mortier, L.; Hassel, J. C.; Rutkowski, P.; McNeil, C.; Kalinka-Warzocha, E.; Savage, K. J.; Hernberg, M. M.; Lebbe, C.; Charles, J.; Mihalcioiu, C.; Chiarion-Sileni, V.; Mauch, C.; Cognetti, F.; Arance, A.; Schmidt, H.; Schadendorf, D.; Gogas, H.; Lundgren-Eriksson, L.; Horak, C.; Sharkey, B.; Waxman, I. M.; Atkinson, V.; Ascierto, P. A. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015, 372 (4), 320-330. (42) Larkin, J.; Chiarion-Sileni, V.; Gonzalez, R.; Grob, J. J.; Cowey, C. L.; Lao, C. D.; Schadendorf, D.; Dummer, R.; Smylie, M.; Rutkowski, P.; Ferrucci, P. F.; Hill, A.; Wagstaff, J.; Carlino, M. S.; Haanen, J. B.; Maio, M.; Marquez-Rodas, I.; McArthur, G. A.; Ascierto, P. A.; Long, G. V.; Callahan, M. K.; Postow, M. A.; Grossmann, K.; Sznol, M.; Dreno, B.; Bastholt, L.; Yang, A.; Rollin, L. M.; Horak, C.; Hodi, F. S.; Wolchok, J. D. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med 2015, 373 (1), 23-34. (43) Reck, M.; Rodriguez-Abreu, D.; Robinson, A. G.; Hui, R.; Csoszi, T.; Fulop, A.; Gottfried, M.; Peled, N.; Tafreshi, A.; Cuffe, S.; O'Brien, M.; Rao, S.; Hotta, K.; Leiby, M. A.; Lubiniecki, G. M.; Shentu, Y.; Rangwala, R.; Brahmer, J. R. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med 2016, 375 (19), 1823-1833. (44) Ferrara, N.; Hillan, K. J.; Gerber, H. P.; Novotny, W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 2004, 3 (5), 391-400. (45) Nahta, R.; Yu, D.; Hung, M. C.; Hortobagyi, G. N.; Esteva, F. J. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol 2006, 3 (5), 269-280. (46) Jonker, D. J.; O'Callaghan, C. J.; Karapetis, C. S.; Zalcberg, J. R.; Tu, D.; Au, H. J.; Berry, S. R.; Krahn, M.; Price, T.; Simes, R. J.; Tebbutt, N. C.; van Hazel, G.; Wierzbicki, R.; Langer, C.; Moore, M. J. Cetuximab for the treatment of colorectal cancer. N Engl J Med 2007, 357 (20), 2040-2048. (47) Price, T. J.; Peeters, M.; Kim, T. W.; Li, J.; Cascinu, S.; Ruff, P.; Suresh, A. S.; Thomas, A.; Tjulandin, S.; Zhang, K.; Murugappan, S.; Sidhu, R. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol 2014, 15 (6), 569-579. (48) Chaney, S. G.; Campbell, S. L.; Bassett, E.; Wu, Y. Recognition and processing of cisplatin- and oxaliplatin-DNA adducts. Crit Rev Oncol Hematol 2005, 53 (1), 3-11. (49) Pfeiffer, P.; Qvortrup, C.; Eriksen, J. G. Current role of antibody therapy in patients with metastatic colorectal cancer. Oncogene 2007, 26 (25), 3661-3678. (50) Weber, J.; McCormack, P. L. Panitumumab: in metastatic colorectal cancer with wild-type KRAS. BioDrugs 2008, 22 (6), 403-411. (51) Amado, R. G.; Wolf, M.; Peeters, M.; Van Cutsem, E.; Siena, S.; Freeman, D. J.; Juan, T.; Sikorski, R.; Suggs, S.; Radinsky, R.; Patterson, S. D.; Chang, D. D. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008, 26 (10), 1626-1634. (52) Thomas, A.; Teicher, B. A.; Hassan, R. Antibody-drug conjugates for cancer therapy. Lancet Oncol 2016, 17 (6), e254-e262. (53) Fang, J.; Nakamura, H.; Maeda, H. 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 2011, 63 (3), 136-151. (54) Chen, Y. I.; Peng, C. L.; Lee, P. C.; Tsai, M. H.; Lin, C. Y.; Shih, Y. H.; Wei, M. F.; Luo, T. Y.; Shieh, M. J. Traceable Self-Assembly of Laser-Triggered Cyanine-Based Micelle for Synergistic Therapeutic Effect. Adv Healthc Mater 2015, 4 (6), 892-902. (55) Mura, S.; Nicolas, J.; Couvreur, P. Stimuli-responsive nanocarriers for drug delivery. Nat Mater 2013, 12 (11), 991-1003. (56) Parveen, S.; Misra, R.; Sahoo, S. K. Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine : nanotechnology, biology, and medicine 2012, 8 (2), 147-166. (57) Murthy, S. K. Nanoparticles in modern medicine: state of the art and future challenges. Int J Nanomedicine 2007, 2 (2), 129-141. (58) Jeon, J. O.; Kim, S.; Choi, E.; Shin, K.; Cha, K.; So, I. S.; Kim, S. J.; Jun, E.; Kim, D.; Ahn, H. J.; Lee, B. H.; Lee, S. H.; Kim, I. S. Designed nanocage displaying ligand-specific Peptide bunches for high affinity and biological activity. ACS Nano 2013, 7 (9), 7462-7471. (59) Chen, J. L.; Tsai, Y. C.; Tsai, M. H.; Lee, S. Y.; Wei, M. F.; Kuo, S. H.; Shieh, M. J. Prominin-1-Specific Binding Peptide-Modified Apoferritin Nanoparticle Carrying Irinotecan as a Novel Radiosensitizer for Colorectal Cancer Stem-Like Cells. Particle & Particle Systems Characterization 2017, 34 (5), 1600424. (60) Desideri, A.; Stefanini, S.; Polizio, F.; Petruzzelli, R.; Chiancone, E. Iron entry route in horse spleen apoferritin. Involvement of the three-fold channels as probed by selective reaction of cysteine-126 with the spin label 4-maleimido-tempo. FEBS Lett 1991, 287 (1-2), 10-14. (61) Clegg, G. A.; Stansfield, R. F.; Bourne, P. E.; Harrison, P. M. The structure and heavy-metal-ion-binding sites of horse spleen apoferritin. Biochem Soc Trans 1980, 8 (5), 654-655. (62) William-Faltaos, S.; Rouillard, D.; Lechat, P.; Bastian, G. Cell cycle arrest and apoptosis induced by oxaliplatin (L-OHP) on four human cancer cell lines. Anticancer Res 2006, 26 (3A), 2093-2099. (63) Adams, P. C.; Powell, L. W.; Halliday, J. W. Isolation of a human hepatic ferritin receptor. Hepatology 1988, 8 (4), 719-721. (64) Huang, X.; El-Sayed, I. H.; Qian, W.; El-Sayed, M. A. Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J Am Chem Soc 2006, 128 (6), 2115-2120. (65) Kennedy, J. E. High-intensity focused ultrasound in the treatment of solid tumours. Nat Rev Cancer 2005, 5 (4), 321-327. (66) Oliveira, H.; Perez-Andres, E.; Thevenot, J.; Sandre, O.; Berra, E.; Lecommandoux, S. Magnetic field triggered drug release from polymersomes for cancer therapeutics. J Control Release 2013, 169 (3), 165-170. (67) Gao, L.; Zhuang, J.; Nie, L.; Zhang, J.; Zhang, Y.; Gu, N.; Wang, T.; Feng, J.; Yang, D.; Perrett, S.; Yan, X. Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nat Nanotechnol 2007, 2 (9), 577-583. (68) Zhen, Z.; Tang, W.; Chuang, Y. J.; Todd, T.; Zhang, W.; Lin, X.; Niu, G.; Liu, G.; Wang, L.; Pan, Z.; Chen, X.; Xie, J. Tumor vasculature targeted photodynamic therapy for enhanced delivery of nanoparticles. ACS Nano 2014, 8 (6), 6004-6013. (69) Joyce, J. A.; Fearon, D. T. T cell exclusion, immune privilege, and the tumor microenvironment. Science 2015, 348 (6230), 74-80. (70) Muhammad, F.; Guo, M.; Qi, W.; Sun, F.; Wang, A.; Guo, Y.; Zhu, G. pH-Triggered controlled drug release from mesoporous silica nanoparticles via intracelluar dissolution of ZnO nanolids. J Am Chem Soc 2011, 133 (23), 8778-8781. (71) Liu, J.; Pang, Y.; Zhu, Z.; Wang, D.; Li, C.; Huang, W.; Zhu, X.; Yan, D. Therapeutic nanocarriers with hydrogen peroxide-triggered drug release for cancer treatment. Biomacromolecules 2013, 14 (5), 1627-1636. (72) Andresen, T. L.; Thompson, D. H.; Kaasgaard, T. Enzyme-triggered nanomedicine: drug release strategies in cancer therapy. Mol Membr Biol 2010, 27 (7), 353-363. (73) Zhang, M.; Murakami, T.; Ajima, K.; Tsuchida, K.; Sandanayaka, A. S.; Ito, O.; Iijima, S.; Yudasaka, M. Fabrication of ZnPc/protein nanohorns for double photodynamic and hyperthermic cancer phototherapy. Proc Natl Acad Sci U S A 2008, 105 (39), 14773-14778. (74) Wu, D.; Huang, L.; Jiang, M. S.; Jiang, H. Contrast agents for photoacoustic and thermoacoustic imaging: a review. Int J Mol Sci 2014, 15 (12), 23616-23639. (75) Hwang, S.; Nam, J.; Jung, S.; Song, J.; Doh, H.; Kim, S. Gold nanoparticle-mediated photothermal therapy: current status and future perspective. Nanomedicine (Lond) 2014, 9 (13), 2003-2022. (76) Kuo, W. S.; Chang, Y. T.; Cho, K. C.; Chiu, K. C.; Lien, C. H.; Yeh, C. S.; Chen, S. J. Gold nanomaterials conjugated with indocyanine green for dual-modality photodynamic and photothermal therapy. Biomaterials 2012, 33 (11), 3270-3278. (77) Wang, Y.; Liu, T.; Zhang, E.; Luo, S.; Tan, X.; Shi, C. Preferential accumulation of the near infrared heptamethine dye IR-780 in the mitochondria of drug-resistant lung cancer cells. Biomaterials 2014, 35 (13), 4116-4124. (78) Yue, C.; Liu, P.; Zheng, M.; Zhao, P.; Wang, Y.; Ma, Y.; Cai, L. IR-780 dye loaded tumor targeting theranostic nanoparticles for NIR imaging and photothermal therapy. Biomaterials 2013, 34 (28), 6853-6861. (79) Zheng, C.; Zheng, M.; Gong, P.; Jia, D.; Zhang, P.; Shi, B.; Sheng, Z.; Ma, Y.; Cai, L. Indocyanine green-loaded biodegradable tumor targeting nanoprobes for in vitro and in vivo imaging. Biomaterials 2012, 33 (22), 5603-5609. (80) Zhang, Y.; He, L.; Wu, J.; Wang, K.; Wang, J.; Dai, W.; Yuan, A.; Hu, Y. Switchable PDT for reducing skin photosensitization by a NIR dye inducing self-assembled and photo-disassembled nanoparticles. Biomaterials 2016, 107, 23-32. (81) Huang, P.; Rong, P.; Jin, A.; Yan, X.; Zhang, M. G.; Lin, J.; Hu, H.; Wang, Z.; Yue, X.; Li, W.; Niu, G.; Zeng, W.; Wang, W.; Zhou, K.; Chen, X. Dye-loaded ferritin nanocages for multimodal imaging and photothermal therapy. Adv Mater 2014, 26 (37), 6401-6408. (82) Peng, C. L.; Shih, Y. H.; Lee, P. C.; Hsieh, T. M.; Luo, T. Y.; Shieh, M. J. Multimodal image-guided photothermal therapy mediated by 188Re-labeled micelles containing a cyanine-type photosensitizer. ACS Nano 2011, 5 (7), 5594-5607. (83) Zhang, C.; Wang, S.; Xiao, J.; Tan, X.; Zhu, Y.; Su, Y.; Cheng, T.; Shi, C. Sentinel lymph node mapping by a near-infrared fluorescent heptamethine dye. Biomaterials 2010, 31 (7), 1911-1917. (84) Bahmani, B.; Bacon, D.; Anvari, B. Erythrocyte-derived photo-theranostic agents: hybrid nano-vesicles containing indocyanine green for near infrared imaging and therapeutic applications. Sci Rep 2013, 3, 2180. (85) Ma, X.; Sreejith, S.; Zhao, Y. Spacer intercalated disassembly and photodynamic activity of zinc phthalocyanine inside nanochannels of mesoporous silica nanoparticles. ACS Appl Mater Interfaces 2013, 5 (24), 12860-12868. (86) Liu, Z.; Robinson, J. T.; Sun, X.; Dai, H. PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. J Am Chem Soc 2008, 130 (33), 10876-10877. (87) Hariri, G.; Edwards, A. D.; Merrill, T. B.; Greenbaum, J. M.; van der Ende, A. E.; Harth, E. Sequential targeted delivery of paclitaxel and camptothecin using a cross-linked 'nanosponge' network for lung cancer chemotherapy. Mol Pharm 2014, 11 (1), 265-275. (88) Aydin, O.; Youssef, I.; Yuksel Durmaz, Y.; Tiruchinapally, G.; ElSayed, M. E. Formulation of Acid-Sensitive Micelles for Delivery of Cabazitaxel into Prostate Cancer Cells. Mol Pharm 2016, 13 (4), 1413-1429. (89) De Jong, W. H.; Borm, P. J. Drug delivery and nanoparticles:applications and hazards. Int J Nanomedicine 2008, 3 (2), 133-149. (90) Shi, J.; Kantoff, P. W.; Wooster, R.; Farokhzad, O. C. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer 2017, 17 (1), 20-37. (91) Zolnik, B. S.; Gonzalez-Fernandez, A.; Sadrieh, N.; Dobrovolskaia, M. A. Nanoparticles and the immune system. Endocrinology 2010, 151 (2), 458-465. (92) Fracasso, G.; Falvo, E.; Colotti, G.; Fazi, F.; Ingegnere, T.; Amalfitano, A.; Doglietto, G. B.; Alfieri, S.; Boffi, A.; Morea, V.; Conti, G.; Tremante, E.; Giacomini, P.; Arcovito, A.; Ceci, P. Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness. J Control Release 2016, 239, 10-18. (93) Golla, K.; Bhaskar, C.; Ahmed, F.; Kondapi, A. K. A target-specific oral formulation of Doxorubicin-protein nanoparticles: efficacy and safety in hepatocellular cancer. J Cancer 2013, 4 (8), 644-652. (94) Galvez, N.; Sanchez, P.; Dominguez-Vera, J. M. Preparation of Cu and CuFe Prussian Blue derivative nanoparticles using the apoferritin cavity as nanoreactor. Dalton Trans 2005, (15), 2492-2494. (95) Ensign, D.; Young, M.; Douglas, T. Photocatalytic synthesis of copper colloids from CuII by the ferrihydrite core of ferritin. Inorg Chem 2004, 43 (11), 3441-3446. (96) Ueno, T.; Suzuki, M.; Goto, T.; Matsumoto, T.; Nagayama, K.; Watanabe, Y. Size-selective olefin hydrogenation by a Pd nanocluster provided in an apo-ferritin cage. Angew Chem Int Ed Engl 2004, 43 (19), 2527-2530. (97) Wang, Z.; Huang, P.; Jacobson, O.; Liu, Y.; Lin, L.; Lin, J.; Lu, N.; Zhang, H.; Tian, R.; Niu, G.; Liu, G.; Chen, X. Biomineralization-Inspired Synthesis of Copper Sulfide-Ferritin Nanocages as Cancer Theranostics. ACS Nano 2016, 10 (3), 3453-3460. (98) Liang, M.; Fan, K.; Zhou, M.; Duan, D.; Zheng, J.; Yang, D.; Feng, J.; Yan, X. H-ferritin-nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection. Proc Natl Acad Sci U S A 2014, 111 (41), 14900-14905. (99) Zhao, Y.; Liang, M.; Li, X.; Fan, K.; Xiao, J.; Li, Y.; Shi, H.; Wang, F.; Choi, H. S.; Cheng, D.; Yan, X. Bioengineered Magnetoferritin Nanoprobes for Single-Dose Nuclear-Magnetic Resonance Tumor Imaging. ACS Nano 2016, 10 (4), 4184-4191. (100) Li, L.; Fang, C. J.; Ryan, J. C.; Niemi, E. C.; Lebron, J. A.; Bjorkman, P. J.; Arase, H.; Torti, F. M.; Torti, S. V.; Nakamura, M. C.; Seaman, W. E. Binding and uptake of H-ferritin are mediated by human transferrin receptor-1. Proc Natl Acad Sci U S A 2010, 107 (8), 3505-3510. (101) Maeda, H.; Wu, J.; Sawa, T.; Matsumura, Y.; Hori, K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 2000, 65 (1-2), 271-284. (102) Lin, X.; Xie, J.; Niu, G.; Zhang, F.; Gao, H.; Yang, M.; Quan, Q.; Aronova, M. A.; Zhang, G.; Lee, S.; Leapman, R.; Chen, X. Chimeric ferritin nanocages for multiple function loading and multimodal imaging. Nano Lett 2011, 11 (2), 814-819. (103) Trott, O.; Olson, A. J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010, 31 (2), 455-461. (104) Granier, T.; Gallois, B.; Dautant, A.; Langlois d'Estaintot, B.; Precigoux, G. Comparison of the structures of the cubic and tetragonal forms of horse-spleen apoferritin. Acta Crystallogr D Biol Crystallogr 1997, 53 (Pt 5), 580-587. (105) Hu, B.; Cui, F.; Yin, F.; Zeng, X.; Sun, Y.; Li, Y. Caffeoylquinic acids competitively inhibit pancreatic lipase through binding to the catalytic triad. Int J Biol Macromol 2015, 80, 529-535. (106) Seeliger, D.; de Groot, B. L. Ligand docking and binding site analysis with PyMOL and Autodock/Vina. J Comput Aided Mol Des 2010, 24 (5), 417-422. (107) Liu, R.; Loll, P. J.; Eckenhoff, R. G. Structural basis for high-affinity volatile anesthetic binding in a natural 4-helix bundle protein. Faseb J 2005, 19 (6), 567-576. (108) Antosiewicz, J. M.; Shugar, D. UV-Vis spectroscopy of tyrosine side-groups in studies of protein structure. Part 2: selected applications. Biophys Rev 2016, 8 (2), 163-177. (109) Fornander, L. H.; Feng, B.; Beke-Somfai, T.; Norden, B. UV transition moments of tyrosine. J Phys Chem B 2014, 118 (31), 9247-9257. (110) Stone, A. L.; Beeler, D.; Oosta, G.; Rosenberg, R. D. Circular dichroism spectroscopy of heparin-antithrombin interactions. Proc Natl Acad Sci U S A 1982, 79 (23), 7190-7194. (111) Kelly, S. M.; Price, N. C. The use of circular dichroism in the investigation of protein structure and function. Curr Protein Pept Sci 2000, 1 (4), 349-384. (112) Lawson, D. M.; Artymiuk, P. J.; Yewdall, S. J.; Smith, J. M.; Livingstone, J. C.; Treffry, A.; Luzzago, A.; Levi, S.; Arosio, P.; Cesareni, G.; et al. Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts. Nature 1991, 349 (6309), 541-544. (113) Haldar, S.; Bevers, L. E.; Tosha, T.; Theil, E. C. Moving Iron through ferritin protein nanocages depends on residues throughout each four alpha-helix bundle subunit. J Biol Chem 2011, 286 (29), 25620-25627. (114) Chou, P. Y.; Fasman, G. D. Empirical predictions of protein conformation. Annu Rev Biochem 1978, 47, 251-276. (115) S Wang, H. D., P Huang, P Sun, X Huang, Y Su, X Zhu, J Shen, D Yan. Real-time self-tracking of an anticancer small molecule nanodrug based on colorful fluorescence variations. RSC Advances 2016, 6 (15), 12472-12478. (116) Skitzki, J. J.; Repasky, E. A.; Evans, S. S. Hyperthermia as an immunotherapy strategy for cancer. Curr Opin Investig Drugs 2009, 10 (6), 550-558. (117) Yang, R., Zhou, Z., Sun, G., Gao, Y., Xu, J., Strappe, P., Blanchard, C., Cheng, Y. and Ding, X. Synthesis of homogeneous protein-stabilized rutin nanodispersions by reversible assembly of soybean (Glycine max) seed ferritin. RSC Adv. 2015, 5 (40), 31533-31540. (118) Liu, T.; Luo, S.; Wang, Y.; Tan, X.; Qi, Q.; Shi, C. Synthesis and characterization of a glycine-modified heptamethine indocyanine dye for in vivo cancer-targeted near-infrared imaging. Drug Des Devel Ther 2014, 8, 1287-1297. (119) Zhang, C.; Liu, T.; Su, Y.; Luo, S.; Zhu, Y.; Tan, X.; Fan, S.; Zhang, L.; Zhou, Y.; Cheng, T.; Shi, C. A near-infrared fluorescent heptamethine indocyanine dye with preferential tumor accumulation for in vivo imaging. Biomaterials 2010, 31 (25), 6612-6617. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/20109 | - |
dc.description.abstract | 發展多功能奈米載體可應用於工程、材料、環境及醫學多方面領域上,尤其將奈米載體應用於癌症治療更是眾多研究學者所關注的議題。多功能性奈米載體可依照其製作的材料特性而賦予不同的功能性角色。現階段常用的多功能性奈米載體主要有微脂體、微胞、樹枝狀聚合物、金奈米粒子、碳管及蛋白質。其中蛋白質載體具有高穩定性、高生物相容性、可降解姓、低毒性及低免疫性的優點,是進一步應用於人體上相對好的奈體載體。
本論文共分成兩個部分進行研究,主要以去鐵鐵蛋白作為藥物運輸的載體,對於癌症的診斷或治療。第一部分為以去鐵鐵蛋白包覆鉑類金屬藥物益樂鉑(oxaliplatin),同時在去鐵鐵蛋白表面接上抗體維必施(panitumumab),用於大腸直腸癌的治療研究。益樂鉑及維必施為對抗轉移性大腸直腸癌病人的第一線用藥。維必施抗體可辨識癌細胞表面的表皮生長因子受體,達到準確的毒殺癌細胞及降低副作用的產生。當蛋白質載體在辨識癌細胞表面時,去鐵鐵蛋白會藉由受體媒介胞吞作用,吞噬入細胞內的溶酶體系統,當去鐵鐵蛋白遇酸性環境時會自然瓦解成次單元,使得鉑類藥物釋放出來。在實驗療效結果顯示,包覆益樂鉑的標靶蛋白質載體能有效的抑制腫瘤的生長並降低其副作用的產生。 第二部分為研究去鐵鐵蛋白結合化療藥物及光感藥物的合併治療。利用去鐵鐵蛋白包覆速溶艾黴素(doxorubicin)後,在其外圍搭載光感藥物ADS-780近紅外光染劑形成顆粒型奈米結構。此顆粒型奈米結構經由光照射後會瓦解進而釋放出蛋白質內部包覆的艾黴素,以此增加腫瘤細胞的毒殺。最後,若將此顆粒型結構藉由尾靜脈注射進入老鼠體內,待24小時腫瘤大量累積蛋白質顆粒後,藉由照射近紅外光可進行熱診斷及治療。實驗結果顯示,在有照光的區域下,腫瘤體積會有效地被抑制且縮小且不造成正常組織的損傷。 整體而言,我們希望建立一個以去鐵鐵蛋白為主,依其中空的特殊結構搭載藥物分子或修飾在其外圍修飾上抗體或胜肽片段作為標靶分子,甚至可以搭載光感藥物,完成後的多功能蛋白質奈米載體可應用於癌症的診斷及標靶治療。 | zh_TW |
dc.description.abstract | The development of multiple functional nanoparticles can be applied in engineering, materials, the environment and medical fields. In particular, nanomedicine has attracted many researchers focusing on cancer treatment. Versatile nanocarriers are given different functional roles depending on the properties of the materials. Commonly used multi-functional nanocarriers mainly include liposomes, micelles, dendrimers, gold nanoparticles, carbon nanotubes, and proteins. Protein carriers have the advantages of high stability, high biocompatibility, biodegradability, low cytotoxicity, and low immunogenicity. Therefore, protein carriers are valuable carriers for further applications in humans.
This dissertation is separated into two parts with the principal research focusing on a drug carrier based on an apoferritin nanocage for cancer diagnosis or treatment. The first part is apoferritin (AF) encapsulated with oxaliplatin and conjugated with panitumumab for the treatment of colorectal cancer. Oxaliplatin and panitumumab have been used as a first-line therapy for metastasis in the treatment of colorectal cancer. Panitumumab has the capability to recognize a tumor cell surface marker called epidermal growth factor receptor (EGFR) and can accurately kill tumor cells and reduce side effects. When protein nanocarriers were targeted the cell surface marker, AF was internalized into the endosome and lysosome through receptor-mediated endocytosis. Then, AF was disassembled into subunits, and the containing drugs were released into acidic environments. The results showed that the oxaliplatin-loaded AF conjugated with panitumumab (AFPO) could inhibit tumor growth and reduce side effects. The second part of the research examines the therapeutic efficacy of a nanocage loaded with a chemotherapy drug and photosensitizer. Apoferritin nanocages were loaded with doxorubicin (AF-DOX NCs), and the ADS-780 molecules were assembled on the surface of AF-DOX NCs to form a homogenously self-assembled structure, called “apoferritin loaded with doxorubicin (DOX) and ADS-780 near-infrared (NIR) fluorescent dye-decorated NPs (ADNIR NPs).” The ADNIR NPs were disrupted into AF-DOX NCs and increased the release of doxorubicin, which enhanced the cytotoxicity. Then, the photothermal theranostics was evaluated by injecting the ADNIR NPs into tumor-bearing mice and then exposing them to an NIR laser light after the nanoparticles substantially accumulated in the tumor site in 24 h. The results showed that the tumor growth was efficiently inhibited under the NIR light irradiation region, and the normal tissue had no obvious damage. In summary, we hope to establish a platform based on an apoferritin nanocage. It has a unique structure, wherein the inner cavity could be loaded with small molecules, and the outer surface could be modified with antibody- or peptide-targeting ligands for chemotherapy. Furthermore, the photosensitizer could also be loaded with nanocages for cancer diagnosis and photothermal therapy. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T02:40:15Z (GMT). No. of bitstreams: 1 ntu-107-D00548016-1.pdf: 5015809 bytes, checksum: 4829b9b7743669e6c59d2cca7c661c85 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 摘要 Ⅰ
Abstract Ⅱ Chapter 1. General introduction 1 Chapter 2. Part. Combination of targeting therapy and chemotherapy Topic: Panitumumab-Conjugated and Platinum-cored pH-sensitive Apoferritin Nanocages for Colorectal Cancer-targeted Therapy 5 Abstract 5 2.1 Introduction 6 2.2 Materials and methods 9 2.3 Results and discussion 18 2.4 Conclusion 27 Figures Figure 1. Schematic diagram of the AFPO nanocages for targeted delivery of chemotherapeutic agents to cancer cells 28 Figure 2. The formation of AFPO nanocages and the morphology of nanocages. (A) The AFPO synthesis links panitumumab on the NHS end, and maleimide derivatives at the other end react with the AFO cysteine group. (B) The morphology of the nanocages was examined and enlarged with zoomed images using TEM microscopy. The TEM image scale bars are 100 nm, and the TEM zoomed image (inset) scale bars are 25 nm 29 Figure 3. Characterization of the AF, AFO, and AFPO nanocages. (A) Size distribution values determined by using a Zetasizer instrument. The particle sizes of the AF, AFO, and AFPO nanocages were 18.12 nm (green line), 18.48 nm (red line), and 24.43 nm (blue line), respectively, and the polydispersity index (PDI) values were 0.227, 0.265, and 0.192, respectively (all < 0.3). (B) Gel-filtration chromatography analysis of AFO and AFPO nanocages. When panitumumab is conjugated to AFO, the gray solid line of the AFO peak is shifted to the left blue dotted line of the AFPO peak, reflecting the increased size of the nanocages 30 Figure 4. AFPO nanocages stability examined by DLS. (A) The size of AFPO nanocages over 24 days. (B) The zeta potential of AFPO nanocages over 24 days 31 Figure 5. The absorbance curve and drug cumulative release profile. (A) The absorbance spectra of AF, AFO, AFPO, and oxaliplatin. (B) The cumulative release of oxaliplatin at different time points under pH 5.0 and pH 7.4 conditions. The results are presented as the mean ± SD (n = 3) 32 Figure 6. EGFR expression in different cell lines and nanocage studies in vitro. (A) EGFR expression in the three cell lines examined by flow cytometry. (B) The ability of AFPO to bind to HT-29 cells was examined by confocal microscopy at 4°C. (C) AFPO labeled with rhodamine dye shows the quantitative cellular uptake at 24 and 48 h. Scale bars = 10 μm in the confocal microscopy images. Error bars represent the means ± SD (n = 3) 33 Figure 7. Cell targeting therapy and competitive cytotoxicity assay. (A) In the SW-620 cells, no significant difference is observed between the AFPO treatment and Pan + AFPO and AFO treatments at 24 or 48 h. (B) In the HCT-116 cells, cell viability was 28.1% in the AFPO group and 36.2% in the AFO group at 24 h; cell viability was 19.9% in the AFPO group and 33.2% in the APO group at 48 h. The difference became significant at 24 h and suppression of cell viability was sustained until 48 h because of slow drug release from the nanocages. In the competitive inhibition assay, only the HCT-116 cells with EGFR overexpression significantly blocked the AFPO targeting ability at 24 or 48 h. Bars represent the means ± SD (n = 3) 34 Figure 8. Apoptosis assay. The annexin V-FITC/PI staining assay of SW-620 and HCT-116 cells incubated with AFPO for 24 and 48 h, analyzed by flow cytometry. (A) The percentage of SW-620 cells showing early apoptosis from no treatment was 3.9% and slightly increased to 4.7% and 6.6% at 24 and 48 h, respectively. (B) The percentage of HCT-116 cells showing early apoptosis increased to 13.3% and 15.5% at 24 and 48 h, respectively 35 Figure 9. Intracellular uptake of rhodamine-labeled AFPO examined by confocal microscopy and quantified according to the fluorescence intensity of the confocal image to show the uptake of rhodamine-labeled AFPO. All cells were observed in a 37°C/5% CO2-incubated environment. The AFPO nanocages are labeled with rhodamine (red), the lysosomes are stained with lysotracker (green), and the nuclei are stained with DAPI (blue). Scale bars = 10 μm 36 Figure 10. Pharmacokinetics of nanocages after a single-dose injection 37 Figure 11. Tumor-targeted therapy in the control (PBS injection) group, free oxaliplatin group, AFO nanocage group, and AFPO nanocage group. The four different formulations were intravenously injected into female BALB/c nude mice bearing SW-620 or HCT-116 tumors. (A) Schedule of treatment. (B) Tumor growth of SW-620 and HCT-116 cells measured every 3 days. (C) Body weight measured every 3 days. The data are presented as the means ± SD (n = 5) 38 Figure 12. The biodistribution of AFPO in the heart, liver, spleen, lung, kidney, and tumor after injection of NIR-797-labeled AFPO into nude mice bearing HCT-116 tumors. (A) Ex vivo IVIS spectrum analysis for 24 h (H, heart; Lv, liver; S, spleen; Lu, lung; K, kidney; T, tumor). (B) NIR fluorescence intensities were quantified from the ex vivo images. (C) NIR-797-labeled AFPO concentration in tissue lysates, indicating the average uptake of nanocages by tumors and visceral organs for 24 h and 48 h. The data are presented as the means ± SD (n = 5) 39 Figure 13. Kaplan–Meier survival analysis and hematoxylin and eosin stain. (A) Survival time of mice bearing SW-620 tumors and HCT-116 tumors. (B) The mice organ tissue sections examined after H&E staining. Scale bars = 100 μm 40 Tables Table 1. Nanocage characteristics and oxaliplatin encapsulation efficiency 41 Table 2. Pharmacokinetics of nanocages 42 Chapter 3. Part. Combination of chemotherapy and photothermal theranostics Topic: Near-Infrared Fluorescent Dye-decorated Nanocages to Form Grenade-Like Nanoparticles with Dual Control Release for Photothermal Theranostics and Chemotherapy 43 Abstract 43 3.1 Introduction 44 3.2 Materials and methods 48 3.3 Results and discussion 57 3.4 Conclusion 68 Figures Figure 1. Schematic mechanism of dual drug controlled release and the cancer treatment process of apoferritin loaded with doxorubicin (DOX) and ADS-780 near infrared (NIR) fluorescent dye-decorated NPs (ADNIR NPs). (A) Loading procedures of doxorubicin (DOX) and ADS-780 NIR dye. (B) ADNIR NPs act as a grenade to detonate the targeted tumor site following laser irradiation (PTT) and explode into cluster warheads (apoferritin-loaded DOX nanocages, AF-DOX NCs) that further destroy the tumor cells (chemotherapy). (C) Illustration of the mechanism of dual drug controlled release and the cancer treatment process of ADNIR NPs 69 Figure 2. Characteristics of ADNIR NPs and morphology of AF NCs, AF-DOX NCs, ADNIR NPs, and ADNIR NPs plus laser light examined by transmission electron microscopy. (A) The size of the ADNIR NPs was measured using dynamic light scattering. (B) Transmission electron microscopy images of apoferritin nanocages (AF NCs), apoferritin-loaded doxorubicin (DOX) nanocages (AF-DOX NCs), apoferritin loaded with DOX and ADS-780 near infrared (NIR) fluorescent dye-decorated NPs (ADNIR NPs), and laser-irradiated ADNIR NPs. Yellow arrows indicate the location of ADNIR NPs. Scale bar = 100 nm 71 Figure 3. The docking image shows the binding of ADS-780 NIR dye (depicted in green) to horse spleen apoferritin 73 Figure 4. (A) Circular dichroism spectra of AF-DOX NCs and ADNIR NPs with different D/P ratios. (B) The NIR fluorescence of ADS-780 NIR dye in PBS, ADS-780 NIR dye in DMSO, ADNIR NPs in PBS, and laser-irradiated ADNIR NPs in PBS. (C) The DOX fluorescence of free DOX in PBS, AF-DOX NCs in PBS, ADNIR NPs in PBS, and laser-irradiated ADNIR NPs in PBS 74 Figure 5. The stability and absorbance status of ADNIR NPs. (A) Dynamic light scattering measurements showed no significant change in the size of ADNIR NPs over a period of 14 days. (B) The zeta potential of ADNIR NPs over a period of 14 days. (C) The zeta potentials of the synthesis steps of AF NCs, AF-DOX NCs, and ADNIR NPs. (D) The distribution of absorbance peaks of free DOX in PBS, free ADS-780 NIR dye in DMSO, AF NCs, AF-DOX NCs, and ADNIR NPs in PBS 75 Figure 6. The nanocages size and the mean of counting rate changed with the different pH conditions. (A) The nanocages were disassemble in lower pH value and reassemble in neutral pH conditions. (B) The mean of counting rate decreased when the pH changed from acid to neutral environments 76 Figure 7. Examination of AF structure in acidic conditions 77 Figure 8. Trends in photothermal temperatures and cumulative drug-release profiles under different conditions. (A) The ADNIR NPs had a high absorbance to NIR light that caused the medium temperature to increase from 25°C to 48.8°C. (B) The cumulative effect of pH and laser light (irradiation was performed for 3 min at 1.2 W/cm2 starting at 0.5 h [denoted by the red arrow]) on drug release. (C) The photothermal efficiency of different drug content of NIR dye. (D) The photothermal efficiency of laser dose. Bars represent the means ± SD (n = 3) 78 Figure 9. Transferrin receptor protein 1 (TfR1) expression level in HT-29 colorectal cancer cell line and examination of ADNIR NP-binding and uptake mechanisms. (A) TfR1 expression of HT-29 cells was measured using flow cytometry. (B) Binding ability of ADNIR NPs to HT-29 cells at 4°C for 1 h. The confocal microscopy images scale bar = 10 μm. (C) DOX was released from ADNIR NPs at 24 and 48 h in response to photoirradiation. (D) ADNIR NPs and apoferritin (AF) (10 mg/mL) cellular uptake competition test measured using a microplate reader. (E) ADNIR NPs and AF (10 mg/mL) cellular uptake competition assay determined using flow cytometry 79 Figure 10. Cytotoxicity of live and dead cells determined using MTT cell proliferation assay and fluorescence microscopy. (A) The optimal treatment concentration of each drug was determined. There were significant differences in apoferritin (AF) between the phosphate-buffered saline (PBS; control) group and the DOX or AF-DOX NCs groups. (B) ADNIR NPs in HT-29 cells were treated for different irradiation times. There were significant differences between without laser-irradiated ADNIR NPs group and laser-irradiated ADNIR NPs group. (C) Fluorescence of live HT-29 cells added with AF in the PBS (control), 808-nm laser irradiation alone, AF-DOX NCs, and laser-irradiated ADNIR NPs groups. The fluorescence microscopy images scale bars = 100 μm 80 Figure 11. Tracking ADNIR NPs using confocal microscopy. (A) Confocal fluorescence images of HT-29 cells to locate ADNIR NPs. (B) The average fluorescence intensity was quantified using ImageJ software. Bars represent the means ± SD (n = 3). The confocal microscopy images scale bar = 10 μm 81 Figure 12. Pharmacokinetic analysis after a single injection 82 Figure 13. Ex Vivo biodistribution of ADNIR NPs in the tissue lysates from tumors and visceral organs at 24 h after intravenous injection 83 Figure 14. In vivo tumor targeting with ADNIR NPs evaluated using IVIS spectrum imaging. (A) ADNIR NPs were intravenously injected for photothermal theranostics and chemotherapy. Scheme of the in vivo treatment schedule. (B) The tumor-targeting effect was observed using IVIS spectrum imaging (the measurement unit for the image display is p/s/cm2/sr) 84 Figure 15. The effect of PTT and monitored tumor temperature of treatment with ADNIR NPs or AF-DOX NCs with 808-nm laser irradiation in vivo. (A) HT-29 tumor growth was inhibited by 808-nm laser irradiation. (B) The highest temperature (62.8°C) of the tumor after the first treatment with ADNIR NPs plus 808-nm laser irradiated regions was compared with treatment with AF-DOX NCs with no obvious increase in temperature (41.8°C) 85 Figure 16. In vivo chemotherapy and PTT antitumor therapeutic efficacy. (A) The tumor inhibition efficacy of mice bearing HT-29 tumors after different treatments. Bars represent the means ± SD (n = 5). (B) Body weights of mice in different treatment groups. (C) Kaplan–Meier survival analysis of mice bearing HT-29 tumors in different treatment groups 86 Figure 17. Hematoxylin & eosin-stained images of major organs and tumor pathological regions. There was no significant change in damage to heart, liver, spleen, lung, and kidney tissues after treatment with ADNIR NPs with laser irradiation. Treatment of tumor tissues with ADNIR NPs with laser light caused significant PTT effects as observed using microscopy. Scale bars = 100 μm 87 Tables Table 1. Characteristics of AF NCs, AF-DOX NCs, ADNIR NPs, and laser-irradiated ADNIR NPs 88 Table 2. Pharmacokinetics of DOX in ADNIR NPs 89 Chapter 4. Conclusion 90 References 92 Appendix: Publications 107 | |
dc.language.iso | en | |
dc.title | 去鐵鐵蛋白奈米載體應用於癌症診斷與治療 | zh_TW |
dc.title | Apoferritin as Nanocarriers for Cancer Diagnosis and Treatment | en |
dc.type | Thesis | |
dc.date.schoolyear | 106-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 林文澧(Win-Li Lin),張富雄(Fu-Hsiung Chang),鍾次文(Tze-Wen Chung),宋信文(Hsing-Wen Sung),陳三元(San-Yuan Chen) | |
dc.subject.keyword | 去鐵鐵蛋白,益樂鉑,維必施,表皮生長因子受體,艾黴素,光感藥物,大腸直腸癌, | zh_TW |
dc.subject.keyword | apoferritin,oxaliplatin,panitumumab,EGFR,doxorubicin,photosensitizer,colorectal cancer, | en |
dc.relation.page | 107 | |
dc.identifier.doi | 10.6342/NTU201800780 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2018-05-07 | |
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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