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Title: 以幾丁聚醣/褐藻醣膠奈米粒攜帶5-氟尿嘧啶結合免疫和化學療法治療癌症
5-FU-Loaded Chitosan/Fucoidan Nanoparticles for Immune and Chemotherapy in Cancer Treatment
Authors: Chen, Shu-Jyun
Contributors: NTOU:Department of Food Science
Keywords: 幾丁聚醣/褐藻醣膠奈米粒;5-氟尿嘧啶;化療;免疫治療;癌症
Chitosan/fucoidan nanoparticals;5-fluorouracil;chemotherapy;Immunotherapy;cancer
Date: 2015
Issue Date: 2018-08-22T06:39:42Z
Abstract: 5-氟尿嘧啶 (5-FU) 是治療癌症的藥物之一;褐藻醣膠具有調節免疫細胞的功能。本研究使用幾丁聚醣/褐藻醣膠功能性奈米粒,包覆 5-FU,期望結合免疫治療和化學療法來治療癌症。以幾丁聚醣與褐藻醣膠重量比 = 5:1 製備奈米粒,以幾丁聚醣/褐藻醣膠奈米粒包覆 5-氟尿嘧啶,奈米粒粒徑為 151.19±9.06 nm、表面電位為 28.11±3.01 mV 以及 PDI 值為 0.22±0.03;使用 HPLC 檢測到包覆率為 73.84±0.83 %、裝載量為 5.03±0.05 %。將幾丁聚醣/褐藻醣膠聚合物與 5-FU 的比例改變,進行體外藥物釋放實驗,結果顯示:聚合物比例變大,則藥物的釋放量較少、釋放較緩慢;藥物比例增大,突釋較快,無法保持長時間釋放。細胞實驗結果顯示,包覆 5-FU 之奈米粒對人類結腸癌細胞株 (HT-29) 有較強的毒殺效果、顯著增加癌細胞的凋亡程度,透過雷射共軛焦掃描電子顯微鏡亦可觀察到奈米粒被 HT-29 細胞攝取;然而此奈米粒對小鼠纖維母細胞 (L929) 並無增強其毒殺效果。此外,包覆 5-FU之奈米粒亦能誘導巨噬細胞 (RAW264.7) 分泌 TNF-α、GM-CSF,進一步調節免疫系統活化。根據上述實驗結果顯示包覆 5-FU 之幾丁聚醣/褐藻醣膠奈米粒系統可經化學和免疫活化來治療癌症,為有潛力的治療癌症藥劑。
5-Fluorouracil (5-FU) is widely used in the treatment of cancer, and fucoidan can function as an adjuvant to regulate immune cells such as enhancing cell maturation and inducing immune responses. In this study, we developed 5-FU coated chitosan/fucoidan (CS/F) functional nanoparticles (NPs), which are expected as a desired treatment to combine immunotherapy with chemotherapy for cancer treatment. As the CS to F weight ratio was 5:1, the NP shows the best performance. Its diameter was 151.19 ± 9.06 nm, the zeta potential was 28.11 ± 3.01 mV and PDI was 0.22 ± 0.03. The encapsulation efficiency of 5-FU in CS/F NPs was 73.84 ± 0.83%, the loading capacity was 5.03 ± 0.05%. We observe in vitro drug release by modifying the weight ratio of polymer (CS and F) to 5-FU. As the polymer ratio increases, the release rate and amount of 5-FU are decreased; as 5-FU ratio increases, 5-FU is burst released from NPs and unable to maintain a long time. The 5-FU coated CF/S NPs have a strong toxic effect on colon carcinoma cell line HT-29 cells and can inducing HT-29 cells apoptosis. Furthermore, HT-29 cellular uptake of NPs was observed by confocal laser scanning transmission electron microscope. However, The 5-FU coated CF/S NPs showed no toxic effects on mouse fibroblasts cell line L929. In addition, the 5-FU coated CF/S NPs can induce TNF-α and GM-CSF secretion of macrophage (RAW264.7), and regulate the immune response promptly. According to the results, the 5-FU coated CF/S NPs are potential cancer therapy agents and expected as a desired treatment combining immunotherapy with chemotherapy to treat cancer.
URI: http://ethesys.lib.ntou.edu.tw/cgi-bin/gs32/gsweb.cgi?o=dstdcdr&s=G0010232064.id
Appears in Collections:[食品科學系] 博碩士論文

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