( 您好!臺灣時間:2024/05/20 14:34
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::


研究生(外文):Lin, Xiao-Zhen
論文名稱(外文):The fabrication and characterization of fucoidan-cisplatin conjugate nanoparticles
指導教授(外文):Hsu, Fu-Yin
口試委員(外文):Tsai, Shiao-WenHawng, Pei-An
  • 被引用被引用:0
  • 點閱點閱:400
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
褐藻醣膠是一種硫酸化的多醣並且被證實有許多的免疫調節功能,如:促進T細胞活化,增強抗腫瘤反應,誘導癌細胞走向凋亡路徑等,更可以抑制使癌細胞的藥物外排幫浦進而減少癌細胞的多重抗藥性。順鉑為一種臨床腫瘤治療中廣泛使用的化療藥物。Thakral等人研究指出,鉑(II)原子與陰離子聚合物的負電荷相互作用可能會導致自發性的摺疊,以形成奈米複合物。因此,本研究的目的為製備褐藻醣膠結合順鉑的奈米粒子。所合成的褐藻醣膠-順鉑奈米粒子(FuCis)的粒徑大小介於150到600 nm之間。並且體外細胞實驗顯示FuCis奈米粒子能夠增強免疫細胞活性並且具有良好的化療效果。
Fucoidan is a sulfated polysaccharide and has been demonstrated having a variety of immunomodulatory effects, such as promoting activation of T cells and enhancing anti-tumor responses, inhibit cancer cell drug efflux pump of multidrug resistance. Cisplatin is a widely used as chemotherapy drug in the treatment of human solid tumors. Thakral et al. showed that the interaction of the platinum (II) atom with the negative charge of the anion polymer could cause spontaneous folding to form a nano-conjugate. Hence, the aim of this study was to fabricate the fucoidan-cisplatin conjugate nanoparticles. The diameter of fucoidan-cisplatin conjugate nanoparticles (FuCis) was between 150 and 600 nm. Moreover, the FuCis could enhance the immune activity and reveal a better chemotherapeutic efficiencies in vitro.
1 前言 - 1 -
1.1 Cisplatin順鉑 - 2 -
1.2 EPR效應(Enhanced Permeability and Retention, EPR Effect) - 3 -
1.3 藥物運送系統(Drug-delivery systems, DDS) - 4 -
1.4 多醣藥物載體 - 4 -
1.5 褐藻醣膠 (Fucoidan) - 5 -
1.6 多重抗藥性 (Multidrug resistance, MDR) - 6 -
2 研究動機與目的 - 7 -
3 材料與方法 - 8 -
3.1 材料 - 8 -
3.1.1 藥品 - 8 -
3.1.2 耗材與儀器 - 9 -
3.1.3 細胞株 - 10 -
3.2 方法 - 11 -
3.2.1 FuCis奈米粒子製備 - 12 -
3.2.2 Cisplatin濃度分析 - 12 -
3.2.3 細胞實驗 - 13 -
3.2.4 統計分析方法 - 13 -
4 結果與討論 - 14 -
4.1 FuCis奈米粒子之大小分析 - 14 -
4.2 Cisplatin 濃度分析 - 22 -
4.3 細胞實驗 - 28 -
5 結論 - 34 -
參考文獻: - 35 -

[1] Perez-Herrero E, Fernandez-Medarde A. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. European journal of pharmaceutics and biopharmaceutics. 2015;93:52-79.
[2] van den Eertwegh AJM, Baars A, Pinedo HM. Adjuvant treatment of colorectal cancer: Towards tumor-specific immunotherapies. Cancer metastasis review. 2001;20:101-8.
[3] Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nature medicine. 2004;10:909-15.
[4] McNeel DG. Cellular immunotherapies for prostate cancer. Biomedicine &; pharmacotherapy. 2007;61:315-22.
[5] Lee KW, Jeong D, Na K. Doxorubicin loading fucoidan acetate nanoparticles for immune and chemotherapy in cancer treatment. Carbohydrate polymers. 2013;94:850-6.
[6] Lake RA, Robinson BWS. Opinion - Immunotherapy and chemotherapy - a practical partnership. Nature reviews cancer. 2005;5:397-405.
[7] Shen DW, Pouliot LM, Hall MD, Gottesman MM. Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes. Pharmacological reviews. 2012;64:706-21.
[8] Tsai SW, Yu DS, Tsao SW, Hsu FY. Hyaluronan-cisplatin conjugate nanoparticles embedded in Eudragit S100-coated pectin/alginate microbeads for colon drug delivery. International journal of nanomedicine. 2013;8:2399-407.
[9] Nishiyama N, Okazaki S, Cabral H, Miyamoto M, Kato Y, Sugiyama Y, et al. Novel cisplatin-incorporated polymeric micelles can eradicate solid tumors in mice. Cancer research. 2003;63:8977-83.
[10] Thakral NK, Ray AR, Majumdar DK. Eudragit S-100 entrapped chitosan microspheres of valdecoxib for colon cancer. Journal of materials science-materials in medicine. 2010;21:2691-9.
[11] Al-Malki AL, Sayed AAR. Thymoquinone attenuates cisplatin-induced hepatotoxicity via nuclear factor kappa- beta. BMC complementary and alternative medicine. 2014;14:8.
[12] Uehara T, Horinouchi A, Morikawa Y, Tonomura Y, Minami K, Ono A, et al. Identification of metabolomic biomarkers for drug-induced acute kidney injury in rats. Journal of applied toxicology. 2014;34:1087-95.
[13] Morral-Ruiz G, Melgar-Lesmes P, Solans C, Garcia-Celma MJ. Multifunctional polyurethane-urea nanoparticles to target and arrest inflamed vascular environment: A potential tool for cancer therapy and diagnosis. Journal of controlled release. 2013;171:163-71.
[14] Peer D, Karp JM, Hong S, FaroKhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nature nanotechnology. 2007;2:751-60.
[15] Kibria G, Hatakeyama H, Ohga N, Hida K, Harashima H. The effect of liposomal size on the targeted delivery of doxorubicin to Integrin alpha v beta 3-expressing tumor endothelial cells. Biomaterials. 2013;34:5617-27.
[16] Yang Y, Zhang YM, Chen Y, Chen JT, Liu y. Targeted polysaccharide nanoparticle for adamplatin prodrug delivery. Journal of medicinal chemistry. 2013;56:9725-36.
[17] Al-Jamal WT, Kostarelos K. Liposomes: from a clinically established drug delivery system to a nanoparticle platform for theranostic nanomedicine. Accounts of chemical research. 2011;44:1094-104.
[18] Vallet-Regi M, Colilla M, Gonzalez B. Medical applications of organic-inorganic hybrid materials within the field of silica-based bioceramics. Chemical society reviews. 2011;40:596-607.
[19] Du JZ, Sun TM, Song WJ, Wu J, Wang J. A tumor-acidity-activated charge-conversional nanogel as an intelligent vehicle for promoted tumoral-cell uptake and drug delivery. Angewandte chemie-international edition. 2010;49:3621-6.
[20] Dhar S, Liu Z, Thomale J, Dai HJ, Lippard SJ. Targeted single-wall carbon nanotube-mediated Pt(IV) prodrug delivery using folate as a homing device. Journal of the american chemical society. 2008;130:11467-76.
[21] Li F, Zhang HT, Gu CH, Fan L, Qiao YB, Tao YC, et al. Self-assembled nanoparticles from folate-decorated maleilated pullulan-doxorubicin conjugate for improved drug delivery to cancer cells. Polymer international. 2013;62:165-71.
[22] Cao Y, Gu Y, Ma H, Bai J, Liu LN, Zhao PG, et al. Self-assembled nanoparticle drug delivery systems from galactosylated polysaccharide-doxorubicin conjugate loaded doxorubicin. International journal of biological macromolecules. 2010;46:245-9.
[23] Huang YC, Lam UI. Chitosan/fucoidan ph sensitive nanoparticles for oral delivery system. Journal of the chinese chemical society. 2011;58:779-85.
[24] Huang YC, Chen JK, Lam UI, Chen SY. Preparing, characterizing, and evaluating chitosan/fucoidan nanoparticles as oral delivery carriers. Journal of polymer research. 2014;21.
[25] Liu Z, Tabakman S, Welsher K, Dai H. Carbon nanotubes in biology and medicine: in vitro and in vivo detection, imaging and drug delivery. Nano research. 2009;2:85-120.
[26] Ghaderi S, Ramesh B, Seifalian AM. Fluorescence nanoparticles "quantum dots" as drug delivery system and their toxicity: a review. Journal of drug targeting. 2011;19:475-86.
[27] Li B, Lu F, Wei XJ, Zhao RX. Fucoidan: structure and bioactivity. Molecules. 2008;13:1671-95.
[28] Park SB, Chun KR, Kim JK, Suk K, Jung YM, Lee WH. The differential effect of high and low molecular weight fucoidans on the severity of collagen-induced arthritis in mice. Phytotherapy research. 2010;24:1384-91.
[29] Thinh PD, Menshova RV, Ermakova SP, Anastyuk SD, Ly BM, Zvyagintseva TN. Structural characteristics and anticancer activity of fucoidan from the brown alga sargassum mcclurei. Marine drugs. 2013;11:1456-76.
[30] Nishiguchi T, Jiang Z, Ueno M, Takeshita S, Cho K, Roh S, et al. Reevaluation of bactericidal, cytotoxic, and macrophage-stimulating activities of commercially available Fucus vesiculosus fucoidan. Algae. 2014;29:237-47.
[31] Takai M, Miyazaki Y, Tachibana H, Yamada K. The enhancing effect of fucoidan derived from Undaria pinnatifida on immunoglobulin production by mouse spleen lymphocytes. Bioscience biotechnology and biochemistry. 2014;78:1743-7.
[32] Wu SJ, Don TM, Lin CW, Mi FL. Delivery of berberine using chitosan/fucoidan-taurine conjugate nanoparticles for treatment of defective intestinal epithelial tight junction barrier. Marine drugs. 2014;12:5677-97.
[33] Yang M, Ma C, Sun J, Shao Q, Gao W, Zhang Y, et al. Fucoidan stimulation induces a functional maturation of human monocyte-derived dendritic cells. International immunopharmacology. 2008;8:1754-60.
[34] Jin JO, Zhang W, Du JY, Wong KW, Oda T, Yu Q. Fucoidan can function as an adjuvant in vivo to enhance dendritic cell maturation and function and promote antigen-specific t cell immune responses. Plos one. 2014;9.
[35] Kwak JY. Fucoidan as a marine anticancer agent in preclinical development. Marine drugs. 2014;12:851-70.
[36] Yang M, Ma CH, Sun JT, Shao QQ, Gao WJ, Zhang Y, et al. Fucoidan stimulation induces a functional maturation of human monocyte-derived dendritic cells. International immunopharmacology. 2008;8:1754-60.
[37] Aisa Y, Miyakawa Y, Nakazato T, Shibata H, Saito K, Ikeda Y, et al. Fucoidan induces apoptosis of human HS-Sultan cells accompanied by activation of caspase-3 and down-regulation of ERK pathways. American journal of hematology. 2005;78:7-14.
[38] Choi EM, Kim AJ, Kim YO, Hwang JK. Immunomodulating activity of arabinogalactan and fucoidan in vitro. Journal of medicinal food. 2005;8:446-53.
[39] Zhang W, Du JY, Jiang ZD, Okimura T, Oda T, Yu Q, et al. Ascophyllan purified from ascophyllum nodosum induces th1 and tc1 immune responses by promoting dendritic cell maturation. Marine drugs. 2014;12:4148-64.
[40] Takeda K, Tomimori K, Kimura R, Ishikawa C, Nowling TK, Mori N. Anti-tumor activity of fucoidan is mediated by nitric oxide released from macrophages. International journal of oncology. 2012;40:251-60.
[41] Kimura R, Rokkaku T, Takeda S, Senba M, Mori N. Cytotoxic effects of fucoidan nanoparticles against osteosarcoma. Marine drugs. 2013;11:4267-78.
[42] Hsu HY, Lin TY, Wu YC, Tsao SM, Hwang PA, Shih YW, et al. Fucoidan inhibition of lung cancer in vivo and in vitro: role of the Smurf2-dependent ubiquitin proteasome pathway in TGF beta receptor degradation. Oncotarget. 2014;5:7870-85.
[43] Ahn G, Lee W, Kim KN, Lee JH, Heo SJ, Kang N, et al. A sulfated polysaccharide of ecklonia cava inhibits the growth of colon cancer cells by inducing apoptosis. Excli journal. 2015;14:294-306.
[44] Han YS, Lee JH, Lee SH. Antitumor effects of fucoidan on human colon cancer cells via activation of akt signaling. Biomolecules &; therapeutics. 2015;23:225-32.
[45] Maruyama H, Tamauchi H, Hashimoto M, Nakano T. Antitumor activity and immune response of Mekabu fucoidan extracted from Sporophyll of Undaria pinnatifida. In vivo. 2003;17:245-9.
[46] Masters JRW, Koberle B. Curing metastatic cancer: Lessons from testicular germ-cell tumours. Nature reviews cancer. 2003;3:517-25.
[47] van Wijngaarden J, van Beek E, van Rossum G, van der Bent C, Hoekman K, van der Pluijm G, et al. Celecoxib enhances doxorubicin-induced cytotoxicity in MDA-MB231 cells by NF-kappa B-mediated increase of intracellular doxorubicin accumulation. European journal of cancer. 2007;43:433-42.
[48] Fan L, Li F, Zhang H, Wang Y, Cheng C, Li X, et al. Co-delivery of PDTC and doxorubicin by multifunctional micellar nanoparticles to achieve active targeted drug delivery and overcome multidrug resistance. Biomaterials. 2010;31:5634-42.
[49] Golla ED, Ayres GH. Spectrophotometric determination of platinum with o-phenylenediamine. Talanta. 1973;20:199-210.
[50] Jiang Z, Okimura T, Yamaguchi K, Oda T. The potent activity of sulfated polysaccharide, ascophyllan, isolated from Ascophyllum nodosum to induce nitric oxide and cytokine production from mouse macrophage RAW264.7 cells: Comparison between ascophyllan and fucoidan. Nitric oxide-biology and chemistry. 2011;25:407-15.

註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
第一頁 上一頁 下一頁 最後一頁 top