Skip navigation

DSpace

機構典藏 DSpace 系統致力於保存各式數位資料(如:文字、圖片、PDF)並使其易於取用。

點此認識 DSpace
DSpace logo
English
中文
  • 瀏覽論文
    • 校院系所
    • 出版年
    • 作者
    • 標題
    • 關鍵字
    • 指導教授
  • 搜尋 TDR
  • 授權 Q&A
    • 我的頁面
    • 接受 E-mail 通知
    • 編輯個人資料
  1. NTU Theses and Dissertations Repository
  2. 生命科學院
  3. 生化科技學系
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76811
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor黃楓婷(Feng-Ting Huang)
dc.contributor.authorYan-Jun Chenen
dc.contributor.author陳彥君zh_TW
dc.date.accessioned2021-07-10T21:37:32Z-
dc.date.available2021-07-10T21:37:32Z-
dc.date.copyright2020-08-28
dc.date.issued2020
dc.date.submitted2020-08-19
dc.identifier.citationADAM DF, SARAH EC AND RIHE L. 2013. The Smart Targeting of Nanoparticles. Current Pharmaceutical Design 19: 6315-6329.
ADORNO-CRUZ V AND LIU H. 2019. Regulation and functions of integrin α2 in cell adhesion and disease. Genes Diseases 6: 16-24.
AHN B, LEE S-G, YOON HR, LEE JM, OH HJ, KIM HM AND JUNG Y. 2018. Four-fold Channel-Nicked Human Ferritin Nanocages for Active Drug Loading and pH-Responsive Drug Release. Angewandte Chemie International Edition 57: 2909-2913.
AISEN P AND LISTOWSKY I. 1980. Iron transport and storage proteins. Annual review of biochemistry 49: 357-393.
AKBARZADEH A, REZAEI-SADABADY R, DAVARAN S, JOO SW, ZARGHAMI N, HANIFEHPOUR Y, SAMIEI M, KOUHI M AND NEJATI-KOSHKI K. 2013. Liposome: classification, preparation, and applications. Nanoscale research letters 8: 102.
ARNAOUT MA, GOODMAN SL AND XIONG J-P. 2007. Structure and mechanics of integrin-based cell adhesion. Current Opinion in Cell Biology 19: 495-507.
ASKARI JA, BUCKLEY PA, MOULD AP AND HUMPHRIES MJ. 2009. Linking integrin conformation to function. Journal of Cell Science 122: 165.
ASZODI A, HUNZIKER EB, BRAKEBUSCH C AND FôSSLER R. 2003. β1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis. Genes development 17: 2465-2479.
AUGUSTIN HG AND KOH GY. 2017. Organotypic vasculature: From descriptive heterogeneity to functional pathophysiology. Science 357: eaal2379.
AVRAAMIDES CJ, GARMY-SUSINI B AND VARNER JA. 2008. Integrins in angiogenesis and lymphangiogenesis. Nature Reviews Cancer 8: 604.
AYALA F, CORRAL J, GONZñLEZ-CONEJERO R, SñNCHEZ I, MORALEDA JM AND VICENTE V. 2003. Genetic polymorphisms of platelet adhesive molecules: association with breast cancer risk and clinical presentation. Breast cancer research and treatment 80: 145-154.
BANGHAM AD AND HORNE R. 1964. Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope. Journal of molecular biology 8: 660-IN610.
BATES RC, LINCZ LF AND BURNS GF. 1995. Involvement of integrins in cell survival. Cancer and Metastasis Reviews 14: 191-203.
BEEKMAN KW, COLEVAS AD, COONEY K, DIPAOLA R, DUNN RL, GROSS M, KELLER ET, PIENTA KJ, RYAN CJ AND SMITH D. 2006. Phase II evaluations of cilengitide in asymptomatic patients with androgen-independent prostate cancer: scientific rationale and study design. Clinical genitourinary cancer 4: 299-302.
BELLINI M ET AL. 2014. Protein nanocages for self-triggered nuclear delivery of DNA-targeted chemotherapeutics in Cancer Cells. Journal of Controlled Release 196: 184-196.
BLEEKER FE, MOLENAAR RJ AND LEENSTRA S. 2012. Recent advances in the molecular understanding of glioblastoma. Journal of neuro-oncology 108: 11-27.
BORST AJ, JAMES ZM, ZAGOTTA WN, GINSBERG M, REY FA, DIMAIO F, BACKOVIC M AND VEESLER D. 2017. The therapeutic antibody LM609 selectively inhibits ligand binding to human αvβ3 integrin via steric hindrance. Structure 25: 1732-1739. e1735.
BOZZUTO G AND MOLINARI A. 2015. Liposomes as nanomedical devices. International journal of nanomedicine 10: 975.
BRAET F, WISSE E, BOMANS P, FREDERIK P, GEERTS W, KOSTER A, SOON L AND RINGER S. 2007. Contribution of high‐resolution correlative imaging techniques in the study of the liver sieve in three‐dimensions. Microscopy research and technique 70: 230-242.
CALDERWOOD DA. 2004. Integrin activation. Journal of Cell Science 117: 657.
CHEN L-T AND WEISS L. 1973. The role of the sinus wall in the passage of erythrocytes through the spleen. Blood 41: 529-537.
CHOI HS, LIU W, MISRA P, TANAKA E, ZIMMER JP, IPE BI, BAWENDI MG AND FRANGIONI JV. 2007. Renal clearance of quantum dots. Nature biotechnology 25: 1165-1170.
CHOI J-S, KIM CS AND BERDIS A. 2018. Inhibition of translesion DNA synthesis as a novel therapeutic strategy to treat brain cancer. Cancer research 78: 1083-1096.
CHOQUET D, FELSENFELD DP AND SHEETZ MP. 1997. Extracellular Matrix Rigidity Causes Strengthening of Integrin–Cytoskeleton Linkages. Cell 88: 39-48.
CHOU LYT, MING K AND CHAN WCW. 2011. Strategies for the intracellular delivery of nanoparticles. Chemical Society Reviews 40: 233-245.
DAMS ET, LAVERMAN P, OYEN WJ, STORM G, SCHERPHOF GL, VAN DER MEER JW, CORSTENS FH AND BOERMAN OC. 2000. Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes. Journal of Pharmacology and Experimental Therapeutics 292: 1071-1079.
DANIELS TR, DELGADO T, HELGUERA G AND PENICHET ML. 2006. The transferrin receptor part II: targeted delivery of therapeutic agents into cancer cells. Clinical immunology 121: 159-176.
DEFILLES C, LISSITZKY J-C, MONTERO M-P, ANDR¢ F, PR¢VOT C, DELAMARRE E, MARRAKCHI N, LUIS J AND RIGOT V. 2009. αvβ5/β6 integrin suppression leads to a stimulation of α2β1 dependent cell migration resistant to PI3K/Akt inhibition. Experimental cell research 315: 1840-1849.
DEMALI KA, WENNERBERG K AND BURRIDGE K. 2003. Integrin signaling to the actin cytoskeleton. Current Opinion in Cell Biology 15: 572-582.
DESGROSELLIER JS AND CHERESH DA. 2010a. Integrins in cancer: biological implications and therapeutic opportunities. Nature Reviews Cancer 10: 9.
DESGROSELLIER JS AND CHERESH DA. 2010b. Integrins in cancer: biological implications and therapeutic opportunities. Nature Reviews Cancer 10: 9.
DOSTALOVA S ET AL. 2016. Site-Directed Conjugation of Antibodies to Apoferritin Nanocarrier for Targeted Drug Delivery to Prostate Cancer Cells. ACS Applied Materials Interfaces 8: 14430-14441.
EISELE G, WICK A, EISELE A-C, CL¢MENT PM, TONN J, TABATABAI G, OCHSENBEIN A, SCHLEGEL U, NEYNS B AND KREX D. 2014. Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression. Journal of neuro-oncology 117: 141-145.
FALVO E ET AL. 2016. Improved Doxorubicin Encapsulation and Pharmacokinetics of Ferritin–Fusion Protein Nanocarriers Bearing Proline, Serine, and Alanine Elements. Biomacromolecules 17: 514-522.
FERLAY J, SHIN H AND BRAY F Cancer Incidence and Mortality. Worldwide International Agency for Research on Cancer 2010.
FINAZZI D AND AROSIO P. 2014. Biology of ferritin in mammals: an update on iron storage, oxidative damage and neurodegeneration. Archives of toxicology 88: 1787-1802.
GAHMBERG CG, FAGERHOLM SC, NURMI SM, CHAVAKIS T, MARCHESAN S AND GRGAO L, ZHUANG J, NIE L, ZHANG J, ZHANG Y, GU N, WANG T, FENG J, YANG D AND PERRETT S. 2007. Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nature nanotechnology 2: 577-583.
GARMY-SUSINI B AND VARNER JA. 2008. Roles of integrins in tumor angiogenesis and lymphangiogenesis. Lymphatic research and biology 6: 155-163.
GEIGER B, SPATZ JP AND BERSHADSKY AD. 2009. Environmental sensing through focal adhesions. Nature Reviews Molecular Cell Biology 10: 21-33.
GERGER A, HOFMANN G, LANGSENLEHNER U, RENNER W, WEITZER W, WEHRSCHGHOSH S, MOHAPATRA S, THOMAS A, BHUNIA D, SAHA A, DAS G, JANA B AND GHOSH S. 2016. Apoferritin Nanocage Delivers Combination of Microtubule and Nucleus Targeting Anticancer Drugs. ACS Applied Materials Interfaces 8: 30824-30832.
GOLDWIRT L, ZAHR N, FARINOTTI R AND FERNANDEZ C. 2013. Development of a new UPLC‐MSMS method for the determination of temozolomide in mice: application to plasma pharmacokinetics and brain distribution study. Biomedical Chromatography 27: 889-893.
GOREN D, HOROWITZ AT, TZEMACH D, TARSHISH M, ZALIPSKY S AND GABIZON A. 2000. Nuclear Delivery of Doxorubicin via Folate-targeted Liposomes with Bypass of Multidrug-resistance Efflux Pump. Clinical Cancer Research 6: 1949.
GURNEY H. 2002. How to calculate the dose of chemotherapy. British journal of cancer 86: 1297.
HALL CL, DUBYK CW, RIESENBERGER TA, SHEIN D, KELLER ET AND VAN GOLEN KL. 2008. Type I collagen receptor (α2β1) signaling promotes prostate cancer invasion through RhoC GTPase. Neoplasia (New York, NY) 10: 797.
HALL CL AND KELLER ET 2017. Analysis of Integrin Alpha2Beta1 (α2β1) Expression as a Biomarker of Skeletal Metastasis. In: PATEL, VB AND PREEDY, VR (Eds.) Biomarkers in Bone Disease, Dordrecht: Springer Netherlands, p. 487-506.
HARRISON PM AND AROSIO P. 1996. The ferritins: molecular properties, iron storage function and cellular regulation. Biochimica et Biophysica Acta (BBA) - Bioenergetics 1275: 161-203.
HIRASAWA M, SHIJUBO N, UEDE T AND ABE S. 1994. Integrin expression and ability to adhere to extracellular matrix proteins and endothelial cells in human lung cancer lines. British journal of cancer 70: 466-473.
HOBBS SK, MONSKY WL, YUAN F, ROBERTS WG, GRIFFITH L, TORCHILIN VP AND JAIN RK. 1998. Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proceedings of the National Academy of Sciences 95: 4607-4612.
HONDA S, SHIROTANI-IKEJIMA H, TADOKORO S, MAEDA Y, KINOSHITA T, TOMIYAMA Y AND MIYATA T. 2009. Integrin-linked kinase associated with integrin activation. Blood 113: 5304-5313.
HOOD JD, FRAUSTO R, KIOSSES WB, SCHWARTZ MA AND CHERESH DA. 2003. Differential αv integrin–mediated Ras-ERK signaling during two pathways of angiogenesis. The Journal of cell biology 162: 933-943.
HU P AND LUO B-H. 2013. Integrin bi-directional signaling across the plasma membrane. Journal of Cellular Physiology 228: 306-312.
HUA S AND WU SY. 2013. The use of lipid-based nanocarriers for targeted pain therapies. Frontiers in pharmacology 4: 143.
HUA S AND WU SY. 2018. Advances and challenges in nanomedicine. Frontiers in pharmacology 9: 1397.
HUDES GR, NATHAN F, KHATER C, HAAS N, CORNFIELD M, GIANTONIO B, GREENBERG R, GOMELLA L, LITWIN S AND ROSS E. 1997. Phase II trial of 96-hour paclitaxel plus oral estramustine phosphate in metastatic hormone-refractory prostate cancer. Journal of clinical oncology 15: 3156-3163.
HUMPHRIES JD, BYRON A AND HUMPHRIES MJ. 2006. Integrin ligands at a glance. Journal of Cell Science 119: 3901.
HUVENEERS S, VAN DEN BOUT I, SONNEVELD P, SANCHO A, SONNENBERG A AND DANEN EH. 2007. Integrin αvβ3 controls activity and oncogenic potential of primed c-Src. Cancer research 67: 2693-2700.
IVASKA J AND HEINO J. 2011. Cooperation between integrins and growth factor receptors in signaling and endocytosis. Annual review of cell and developmental biology 27: 291-320.
JEMAL A, SIEGEL R, XU J AND WARD E. 2010. Cancer statistics, 2010. CA: a cancer journal for clinicians 60: 277-300.
JIANG B, ZHANG R, ZHANG J, HOU Y, CHEN X, ZHOU M, TIAN X, HAO C, FAN K AND YAN X. 2019. GRP78-targeted ferritin nanocaged ultra-high dose of doxorubicin for hepatocellular carcinoma therapy. THERANOSTICS 9: 2167-2182.
JUTZ GN, VAN RIJN P, SANTOS MIRANDA B AND BÖKER A. 2015. Ferritin: a versatile building block for bionanotechnology. Chemical reviews 115: 1653-1701.
KAWABATA H. 2019. Transferrin and transferrin receptors update. Free Radical Biology and Medicine 133: 46-54.
KIM M, RHO Y, JIN K, AHN B, JUNG S, KIM H AND REE M. 2011. pH-Dependent Structures of Ferritin and Apoferritin in Solution: Disassembly and Reassembly. Biomacromolecules 12: 1629-1640.
KNIGHT CG, MORTON LF, ONLEY DJ, PEACHEY AR, MESSENT AJ, SMETHURST PA, TUCKWELL DS, FARNDALE RW AND BARNES MJ. 1998. Identification in collagen type I of an integrin α2β1-binding site containing an essential GER sequence. Journal of Biological Chemistry 273: 33287-33294.
KOBAYASHI H, WATANABE R AND CHOYKE PL. 2014. Improving conventional enhanced permeability and retention (EPR) effects; what is the appropriate target? Theranostics 4: 81.
KURUPPU AI, ZHANG L, COLLINS H, TURYANSKA L, THOMAS NR AND BRADSHAW TD. 2015. An apoferritin‐based drug delivery system for the tyrosine kinase inhibitor gefitinib. Advanced healthcare materials 4: 2816-2821.
LAVAN DA, MCGUIRE T AND LANGER R. 2003. Small-scale systems for in vivo drug delivery. Nature biotechnology 21: 1184.
LEE EJ ET AL. 2018. Nanocage-Therapeutics Prevailing Phagocytosis and Immunogenic Cell Death Awakens Immunity against Cancer. Advanced Materials 30: 1705581.
LEE J-O, BANKSTON LA AND ROBERT C LIDDINGTON MAAA. 1995. Two conformations of the integrin A-domain (I-domain): a pathway for activation? Structure 3: 1333-1340.
LI L, FANG CJ, RYAN JC, NIEMI EC, LEBRLI L ET AL. 2010b. Binding and uptake of H-ferritin are mediated by human transferrin receptor-1. Proceedings of the National Academy of Sciences 107: 3505.
LIANG M, FAN K, ZHOU M, DUAN D, ZHENG J, YANG D, FENG J AND YAN X. 2014. H-ferritin–nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection. Proceedings of the National Academy of Sciences 111: 14900.
LIN CY, YANG SJ, PENG CL AND SHIEH MJ. 2018. Panitumumab-Conjugated and Platinum-Cored pH-Sensitive Apoferritin Nanocages for Colorectal Cancer-Targeted Therapy. ACS Appl Mater Interfaces 10: 6096-6106.
LUO B-H, CARMAN CV AND SPRINGER TA. 2007. Structural Basis of Integrin Regulation and Signaling. Annual Review of Immunology 25: 619-647.
MACKENZIE EL, IWASAKI K AND TSUJI Y. 2008. Intracellular iron transport and storage: from molecular mechanisms to health implications. Antioxid Redox Signal 10: 997-1030.
MAEDA H, WU J, SAWA T, MATSUMURA Y AND HORI K. 2000. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. Journal of controlled release 65: 271-284.
MURPHY EA, MAJETI BK, BARNES LA, MAKALE M, WEIS SM, LUTU-FUGA K, WRASIDLO W AND CHERESH DA. 2008. Nanoparticle-mediated drug delivery to tumor vasculature suppresses metastasis. Proceedings of the National Academy of Sciences 105: 9343-9348.
MURTHY SK. 2007. Nanoparticles in modern medicine: state of the art and future challenges. International journal of nanomedicine 2: 129.
NECKERS LM AND TREPEL J. 1986. Transferrin receptor expression and the control of cell growth. Cancer investigation 4: 461-470.
NOTNI J, REICH D, MALTSEV OV, KAPP TG, STEIGER K, HOFFMANN F, ESPOSITO I, WEICHERT W, KESSLER H AND WESTER H-J. 2017. In vivo PET imaging of the cancer integrin αvβ6 using 68Ga-labeled cyclic RGD nonapeptides. Journal of Nuclear Medicine 58: 671-677.
NYKVIST P, TU H, IVASKA J, KôPYLô J, PIHLAJANIEMI T AND HEINO J. 2000. Distinct recognition of collagen subtypes by alpha (1) beta (1) and alpha (2) beta (1) integrins. Alpha (1) beta (1) mediates cell adhesion to type XIII collagen. The Journal of biological chemistry 275: 8255.
PATIL Y, SADHUKHA T, MA L AND PANYAM J. 2009. Nanoparticle-mediated simultaneous and targeted delivery of paclitaxel and tariquidar overcomes tumor drug resistance. Journal of Controlled Release 136: 21-29.
PATIL YB, SWAMINATHAN SK, SADHUKHA T, MA L AND PANYAM J. 2010. The use of nanoparticle-mediated targeted gene silencing and drug delivery to overcome tumor drug resistance. Biomaterials 31: 358-365.
PETROS RA AND DESIMONE JM. 2010. Strategies in the design of nanoparticles for therapeutic applications. Nature Reviews Drug Discovery 9: 615-627.
PINKEL D. 1958. The use of body surface area as a criterion of drug dosage in cancer chemotherapy. Cancer Research 18: 853-856.
PLOW EF, QIN J AND BYZOVA T. 2009. Kindling the flame of integrin activation and function with kindlins. Curr Opin Hematol 16: 323-328.
REYNOLDS LE, WYDER L, LIVELY JC, TAVERNA D, ROBINSON SD, HUANG X, SHEPPARD D, HYNES RO AND HODIVALA-DILKE KM. 2002. Enhanced pathological angiogenesis in mice lacking β 3 integrin or β 3 and β 5 integrins. Nature medicine 8: 27.
RUSTHOVEN CG, KOSHY M, SHER DJ, NEY DE, GASPAR LE, JONES BL, KARAM SD, AMINI A, ORMOND DR AND YOUSSEF AS. 2016. Combined-modality therapy with radiation and chemotherapy for elderly patients with glioblastoma in the temozolomide era: a national cancer database analysis. JAMA neurology 73: 821-828.
SAHOO SK, MISRA R AND PARVEEN S 2017. Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine in Cancer: Pan Stanford, p. 73-124.
SAN ANTONIO J ET AL. 2009. A Key Role for the Integrin α2β1 in Experimental and Developmental Angiogenesis. The American journal of pathology 175: 1338-1347.
SANTAMBROGIO P, LEVI S, AROSIO P, PALAGI L, VECCHIO G, LAWSON DM, YEWDALL SJ, ARTYMIUK PJ, HARRISON PM AND JAPPELLI R. 1992. Evidence that a salt bridge in the light chain contributes to the physical stability difference between heavy and light human ferritins. Journal of Biological Chemistry 267: 14077-14083.
SCHWENDENER RA. 2014. Liposomes as vaccine delivery systems: a review of the recent advances. Therapeutic advances in vaccines 2: 159-182.
SERCOMBE L, VEERATI T, MOHEIMANI F, WU SY, SOOD AK AND HUA S. 2015. Advances and Challenges of Liposome Assisted Drug Delivery. 6.
SOTTNIK JL, DAIGNAULT-NEWTON S, ZHANG X, COLM M, HUSSAIN MH, KELLER ET AND HALL CL 2013. Abstract B49: Integrin alpha2beta1 (α2β1) promotes prostate cancer skeletal metastasis. AACR.
STEICHEN SD, CALDORERA-MOORE M AND PEPPAS NA. 2013. A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics. European journal of pharmaceutical sciences 48: 416-427.
STREULI CH. 2009. Integrins and cell-fate determination. Journal of Cell Science 122: 171.
STUPP R, HEGI ME, GORLIA T, ERRIDGE SC, PERRY J, HONG Y-K, ALDAPE KD, LHERMITTE B, PIETSCH T AND GRUJICIC D. 2014. Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial. The lancet oncology 15: 1100-1108.
SUK JS, XU Q, KIM N, HANES J AND ENSIGN LM. 2016. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Advanced drug delivery reviews 99: 28-51.
SUN T, ZHANG YS, PANG B, HYUN DC, YANG M AND XIA Y. 2014. Engineered nanoparticles for drug delivery in cancer therapy. Angewandte Chemie International Edition 53: 12320-12364.
SZEBENI J AND MOGHIMI SM. 2009. Liposome triggering of innate immune responses: a perspective on benefits and adverse reactions: biological recognition and interactions of liposomes. Journal of liposome research 19: 85-90.
TADOKORO S, SHATTIL SJ, ETO K, TAI V, LIDDINGTON RC, DE PEREDA JM, GINSBERG MH AND CALDERWOOD DA. 2003. Talin Binding to Integrin ß Tails: A Final Common Step in Integrin Activation. Science 302: 103.
TAKADA Y, YE X AND SIMON S. 2007. The integrins. Genome Biology 8: 215.
TAKAHASHI T AND KUYUCAK S. 2003. Functional properties of threefold and fourfold channels in ferritin deduced from electrostatic calculations. Biophysical journal 84: 2256-2263.
THEIL EC. 1987. FERRITIN: STRUCTURE, GENE REGULATION, AND CELLULAR FUNCTION IN ANIMALS, PLANTS, AND MICROORGANISMS. Annual Review of Biochemistry 56: 289-315.
TRAN S, DEGIOVANNI P-J, PIEL B AND RAI P. 2017. Cancer nanomedicine: a review of recent success in drug delivery. Clinical and Translational Medicine 6: 44.
TRINH VA, PATEL SP AND HWU W-J. 2009. The safety of temozolomide in the treatment of malignancies. Expert opinion on drug safety 8: 493-499.
UCHIDA M, KANG S, REICHHARDT C, HARLEN K AND DOUGLAS T. 2010. The ferritin superfamily: Supramolecular templates for materials synthesis. Biochimica et Biophysica Acta (BBA) - General Subjects 1800: 834-845.
VAHED SZ, SALEHI R, DAVARAN S AND SHARIFI S. 2017. Liposome-based drug co-delivery systems in cancer cells. Materials Science and Engineering: C 71: 1327-1341.
VERMA D, GULATI N, KAUL S, MUKHERJEE S AND NAGAICH U. 2018. Protein based nanostructures for drug delivery. Journal of pharmaceutics 2018.
WANG C, ZHANG C, LI Z, YIN S, WANG Q, GUO F, ZHANG Y, YU R, LIU Y AND SU Z. 2018a. Extending Half Life of H-Ferritin Nanoparticle by Fusing Albumin Binding Domain for Doxorubicin Encapsulation. Biomacromolecules 19: 773-781.
WANG W, KNOVICH MA, COFFMAN LG, TORTI FM AND TORTI SV. 2010. Serum ferritin: Past, present and future. Biochimica et Biophysica Acta (BBA) - General Subjects 1800: 760-769.
WANG Z ET AL. 2018b. Metal ion assisted interface re-engineering of a ferritin nanocage for enhanced biofunctions and cancer therapy. Nanoscale 10: 1135-1144.
WELLER M, STEINBACH JP AND WICK W. 2005. Temozolomide: a milestone in the pharmacotherapy of brain tumors.
WEN PY AND KESARI S. 2008. Malignant gliomas in adults. New England Journal of Medicine 359: 492-507.
WHITESIDES GM. 2003. The'right'size in nanobiotechnology. Nature biotechnology 21: 1161.
WINTER PM, CARUTHERS SD, KASSNER A, HARRIS TD, CHINEN LK, ALLEN JS, LACY EK, ZHANG H, ROBERTSON JD AND WICKLINE SA. 2003. Molecular imaging of angiogenesis in nascent Vx-2 rabbit tumors using a novel ανβ3-targeted nanoparticle and 1.5 tesla magnetic resonance imaging. Cancer research 63: 5838-5843.
XU S, OLENYUK BZ, OKAMOTO CT AND HAMM-ALVAREZ SF. 2013. Targeting receptor-mediated endocytotic pathways with nanoparticles: Rationale and advances. Advanced Drug Delivery Reviews 65: 121-138.
YAMEEN B, CHOI WI, VILOS C, SWAMI A, SHI J AND FAROKHZAD OC. 2014. Insight into nanoparticle cellular uptake and intracellular targeting. Journal of Controlled Release 190: 485-499.
ZHEN Z, TANG W, CHEN H, LIN X, TODD T, WANG G, COWGER T, CHEN X AND XIE J. 2013. RGD-Modified Apoferritin Nanoparticles for Efficient Drug Delivery to Tumors. ACS Nano 7: 4830-4837.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76811-
dc.description.abstract近數十年來各式各樣的化學治療藥物已蓬勃被開發。其中,Doxorubicin (DOX) ,俗稱小紅莓,臨床上被應用在許多惡性腫瘤之治療。儘管其具有良好的治療功效,但DOX仍引起許多劑量限制性的副作用,而心臟毒性是主要的副作用,為了減緩副作用,可以透過奈米粒子將化學藥物包裹並專一性傳遞至腫瘤細胞。至今已有多種材料組成的奈米粒子被陸續開發出來。然而,這些奈米粒子的生物相容性和代謝機制限制了它們的臨床應用。最近,因ferritin (鐵蛋白) 的特性而被提出其為奈米粒子的可能性,ferritin是鐵轉運蛋白,由24個單體組成,可以自組裝成球體。由於鐵蛋白具有精確的奈米形狀,高生物安全性,高生物相容性,並且可以包覆多種類型的藥物,因此鐵蛋白具有應用於分子影像和治療的潛力。在本篇研究中,具標靶integrin α2β1的鐵蛋白被生產出來,用於增強其和高表現integrin α2β1的癌細胞的結合能力,而integrin α2β1主要是collagen I (膠原) 的受體,在各種腫瘤細胞中高度表達出來。與未修飾的鐵蛋白相比,具標靶integrin α2β1的鐵蛋白作為奈米載體更有潛力用於腫瘤治療。具標靶integrin 的鐵蛋白顯示出比鐵蛋白有更好的DOX包覆效率和產量。透過共軛焦顯微鏡觀察,具標靶integrin的鐵蛋白在兩株具高integrin α2β1表現量的細胞株-U-87 MG和PC3細胞上顯示出較好的細胞結合力,另外,在U-87 MG和PC3細胞中,具標靶integrin的鐵蛋白包覆DOX比鐵蛋白包覆DOX和DOX相比,具有較高的細胞毒性。在小鼠腫瘤模式實驗中,包覆著DOX的標靶integrin的鐵蛋白明顯地能抑制腫瘤生長以及具有標的腫瘤的能力。根據我們的研究結果,顯現具標靶integrin的鐵蛋白具有成為新型的抗癌奈米載體的潛力。zh_TW
dc.description.abstractVarious potent chemotherapeutic drugs have been developed over decades. Doxorubicin (DOX) has clinically usage in a wide range of malignancies. Despite its profound therapeutic efficacy, DOX causes numerous dose-limiting side effects and cardiotoxicity is the main one. To eliminate side effects, targeted delivery of chemo-drugs to tumor cells can be achieved via nanoparticles. Many promising nanoparticles consisted of various materials have been developed. However, biocompatibility and metabolism issues related to these nanoparticles have limited their clinical applications. Recently, ferritin which is iron-transport protein consisting of 24 subunits that could self-assemble into a shell-like sphere, have been investigated. Because ferritin have the precisely nanoscale shape, high biosafety, high biocompatibility, and could encapsulate many types of drugs, ferritin has the potential for in vivo imaging and therapeutic agent. In this study, integrin-targeted ferritin with the integrin α2β1-targeting peptide on the ferritin surface was produced to enhance and specifically target cancer cells with high expression of integrin α2β1, a major collagen receptor that highly expresses on various tumor cells. In comparison with unmodified ferritin, integrin-targeted ferritin has enhanced potential as nanoveichle for tumor therapy. Integrin-targeted ferritin showed higher DOX loading efficiency and yield than ferritin. Integrin-targeted ferritin showed strong cellular binding on U-87 MG and PC3 cells by confocal microscopy. Moreover, DOX-encapsulated integrin-targeted ferritin showed higher cytotoxicity effects than DOX-encapsulated ferritin and free DOX in U-87 MG and PC3 cells. Furthermore, DOX-encapsulated integrin-targeted ferritin showed significant inhibition of tumor growth and accumulation in tumors in vivo. All of our findings supported that integrin α2β1-targeted ferritin has the potential to be a novel anticancer nanomedicine.
en
dc.description.provenanceMade available in DSpace on 2021-07-10T21:37:32Z (GMT). No. of bitstreams: 1
U0001-1708202014150200.pdf: 4326489 bytes, checksum: 11a5a7191db07d691379c5fae49a1438 (MD5)
Previous issue date: 2020
en
dc.description.tableofcontents口試委員審定書 1
致謝 2
中文摘要 3
Abstract 4
Abbreviations 5
Content 6
Chapter 1 Introduction 9
1.1 Chemotherapy for cancer treatment 9
1.2 Nanoparticle design for drug delivery in cancer treatment 11
1.3 Clinical application of liposome: advantage and disadvantage 14
1.4 Ferritin 17
1.4.1 Characteristics and function of ferritin 17
1.4.2 Transferrin and Transferrin receptor 18
1.4.3 The potential of ferritin as carriers for biomedical application 19
1.5 Integrin 20
1.5.1 Characteristics and function of integrin 20
1.5.2 Integrin in cancer 22
1.5.3 Integrin a2b1 and the role of integrin a2b1 in cancer progression 24
1.5.4 Target integrin as cancer therapy 25
1.6 Research purpose 27
Chapter 2 Materials and Methods 29
2.1 Recombinant protein preparation 29
2.1.1 BL21(DE3) expression system 29
2.1.2 Protein induction 29
2.1.3 Protein purification 29
2.2 Protein analysis 30
2.2.1 Gel electrophoresis 30
2.2.2 CBR staining 31
2.3 Protein properties analysis (Self-assembly test) 31
2.4 Protein application 31
2.4.1 Labeling of protein 31
2.4.2 Formation of protein-DOX 32
2.4.2.1 Cu2+-DOX complex formation 32
2.4.2.2 Cu2+-DOX complex encapsulation into protein 33
2.4.2.3 DOX encapsulation into protein through assembly and disassembly 33
2.4.2.4 Encapsulation efficiency and yield 34
2.4.3 Drug release test 34
2.5 Cell culture 34
2.6 Cellular protein extraction 35
2.7 Immunoblotting 35
2.8 Cell viability analysis 36
2.9 Cellular uptake of DOX in cancer cells 37
2.10 Flow cytometry analysis of protein binding on cancer cells 38
2.11 Confocal imaging analysis of protein binding on cancer cells 38
2.12 Confocal imaging analysis of DOX uptake on cancer cells 39
2.13 Establishing animal models 39
2.14 Biodistribution and tumor-targeting ability of protein 39
2.15 In vivo tumor therapy study 40
2.16 Histological Analysis 40
Chapter 3 Results 41
3.1 Ferritin (FRT) and 2DGEA-modified ferritin (2DFRT) preparation 41
3.2 Disassembly and reassembly of 2DFRT by pH alteraction 41
3.3 Comparison of transferrin receptor 1 (TfR1) and integrin α2β1 expression in various cancer cells and normal cells 42
3.4 Receptor-mediated cellular binding of 2DFRT on cancer cells 43
3.5 Quantification of 2DFRT binding on cancer cells 43
3.6 2DFRT translocated into nucleus on cancer cells 45
3.7 Generation of FRT-DOX and 2DFRT-DOX 45
3.8 In vitro drug release profiles of 2DFRT-DOX 46
3.9 Internalization of 2DFRT-FITC-DOX and nuclear translocation of DOX on cancer cells 46
3.10 Quantification of cellular uptake of cancer cells 49
3.11 Cell cytotoxicity of 2DFRT-DOX on cancer cells 50
3.12 In vivo tumor binding and biodistribution of 2DFRT 51
3.13 In vivo therapy studies of 2DFRT-DOX 52
Chapter 4 Discussion 54
4.1 The rational design of nanoparticle for drug delivery: Is ferritin an ideal nanoparticle for tumor-targeted therapy 54
4.2 Dilemma for using metal ions to encapsulate DOX into ferritin 55
4.3 The comparison of the cytotoxicity effect of drug loaded particle with free drug 57
4.4 Unexpected results of cell cytotoxicity and drug uptake in the normal cell line(RWPE1 cells) 58
Chapter 5 Summary and Future Prospects 60
Chapter 6 References 62
Figures 72
Figure 1. The purified recombinant FRT and 2DFRT from E. coli BL21(DE3) expression system 73
Figure 2. The pH-dependent disassembly and reassembly of 2DFRT 74
Figure 3. The Eexpression levels of transferrin receptor 1 (TfR1), integrin α2 and β1 in different cell lines
integrin α2β1 in different cell lines 75
Figure 4. Binding of 2DFRT-FITC and FRT-FITC on cancer cells 77
Figure 5. 2DFRT and FRT bound to the cell surface of various cancer cells 80
Figure 6. 2DFRT translocated into nucleus 82
Figure 7. The optimization of drug encapsulation 84
Figure 8. The drug cumulative release profile under different pH conditions 85
Figure 9. Internalization of 2DFRT-FITC-DOX and nuclear translocation of DOX in cancer cells 86
Figure 10. Quantification of DOX cellular uptake on cancer cells 91
Figure 11. Cell cytotoxicity of 2DFRT-DOX on various cancer cells 94
Figure 12. In vivo tumor binding and biodistribution of 2DFRT 97
Figure 13. The therapeutic studies of 2DFRT-DOX on glioblastoma mouse models 100
Appendixes 103
dc.language.isoen
dc.subject鐵蛋白zh_TW
dc.subject阿黴素zh_TW
dc.subject具標靶integrin的鐵蛋白zh_TW
dc.subjectferritinen
dc.subjectintegrin-targeted ferritinen
dc.subjectdoxorubicinen
dc.title可標靶integrin的鐵蛋白奈米載體於癌症治療之研究zh_TW
dc.titleStudies of integrin-targeting ferritin nanocages for cancer therapyen
dc.typeThesis
dc.date.schoolyear108-2
dc.description.degree碩士
dc.contributor.oralexamcommittee張世宗 (Shih-Chung Chang),廖憶純(Yi-Chun Liao),林晉玄 (Ching-Hsuan Lin),吳亘承 (Hsuan-Chen Wu)
dc.subject.keyword鐵蛋白,具標靶integrin的鐵蛋白,阿黴素,zh_TW
dc.subject.keywordferritin,integrin-targeted ferritin,doxorubicin,en
dc.relation.page103
dc.identifier.doi10.6342/NTU202003741
dc.rights.note未授權
dc.date.accepted2020-08-20
dc.contributor.author-college生命科學院zh_TW
dc.contributor.author-dept生化科技學系zh_TW
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 
U0001-1708202014150200.pdf
  未授權公開取用
4.23 MBAdobe PDF
顯示文件簡單紀錄


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。

社群連結
聯絡資訊
10617臺北市大安區羅斯福路四段1號
No.1 Sec.4, Roosevelt Rd., Taipei, Taiwan, R.O.C. 106
Tel: (02)33662353
Email: ntuetds@ntu.edu.tw
意見箱
相關連結
館藏目錄
國內圖書館整合查詢 MetaCat
臺大學術典藏 NTU Scholars
臺大圖書館數位典藏館
本站聲明
© NTU Library All Rights Reserved