研究生: |
李奕楠 Li, Yi-Nan |
---|---|
論文名稱: |
以單核球細胞膜包覆奈米粒子之合成與鑑定 Synthesis and characterization of monocyte membrane-coated nanoparticle |
指導教授: |
江啟勳
Chiang, Chi-Shiun |
口試委員: |
陳芳馨
Chen, Fang-Hsin 張建文 Chang, Chien-Wen |
學位類別: |
碩士 Master |
系所名稱: |
原子科學院 - 生醫工程與環境科學系 Department of Biomedical Engineering and Environmental Sciences |
論文出版年: | 2016 |
畢業學年度: | 104 |
語文別: | 英文 |
論文頁數: | 47 |
中文關鍵詞: | 奈米粒子 、藥物載體 、單核球 、細胞膜 |
外文關鍵詞: | Nanoparticle, Drug delivery, Bone-marrow derived monocyte, Cell membrane |
相關次數: | 點閱:2 下載:0 |
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近年來,以奈米粒子作為藥物載體是一個十分熱門的研究課題。 由於在腫瘤位置的高滲透長滯留(EPR)效應,奈米粒子藉由自身的特性而能夠累積在腫瘤處。除此之外,奈米粒子能夠提高疏水性藥物的溶解度並能夠藉由不同的設計改變藥物釋放的模式,這些特性使得奈米粒子特別適合作為癌症治療的藥物載體。但是外來的奈米粒子容易被單核吞噬細胞系統(RES)所辨識並清除。在奈米粒子表面修飾上聚乙二醇(PEG)能透提高奈米粒子在生物體內的循環時間並在細胞與奈米粒子間產生一個排斥力量,使奈米粒子較不易被RES所清除,但同時也使奈米粒子較不易被腫瘤細胞攝取。不少奈米粒子載體修飾上腫瘤標靶配體像是葉酸,抗體,肽鏈,配體等等以提高奈米粒子在腫瘤處的累積量。近年來,由天然細胞膜所包覆的奈米粒子載體被發展出來,在生物體內產生極低的免疫反應,其在體內循環時間能夠比修飾上PEG的奈米粒子還長。在本論文中,我們建立了一個由具有腫瘤趨向性的單核球細胞膜包覆生物可降解的聚乳酸-甘醇酸(PLGA)高分子核心所製成的奈米藥物載體。我們的結果顯示出單核球所包覆的奈米粒子較不易被巨噬細胞所吞噬,並同時具有腫瘤趨向性。綜合以上成果,由單核球細胞膜所包覆的奈米粒子在腫瘤治療上具有潛力,並值得更深入的研究。
Nanoparticle-based drug delivery system has been intensively studied in recent years. Due to the enhanced permeability and retention (EPR) effect at the tumor region, nanoparticles can accumulate at tumor intrinsically. Additionally, nanoparticles are able to increase the solubility of hydrophobic drug and change the drug release profile depending on the design of the nanoparticle. These characteristics make nanoparticles attractive drug carriers for cancer therapy. However, the extrinsic nanoparticles can be recognized and eliminated by the reticuloendothelial system (RES). In order to prolong the circulation time of nanoparticles, surface modification of polyethylene glycol (PEG) on the nanoparticles can provide a repulsive force against cells resulting in reduced level of the RES recognition. The modification of PEG (PEGylation) also reduces the nanoparticle uptaken by tumor cells. Several nanoparticles with the conjugation of targeting ligands, such as folate, antibodies, peptides, and aptamers, have been developed to enhance the accumulation at tumor site. Recently, cell membrane-coated nanoparticles were developed by coating natural cell membrane on the nanoparticle. The cell membrane-coated nanoparticles exhibit minimum immunogenicity and show a longer circulation time than PEGylated nanoparticles. In this study, we established a monocyte membrane-coated nanoparticle delivery system, coating the cell membrane extracted from tumor-tropic bone marrow-derived monocyte (BMDM) on a biodegradable poly lactic-co-glycolic acid (PLGA) polymeric core. We demonstrate that a reduced engulfment of macrophage in monocyte membrane-coated nanoparticle compared to the bare nanoparticle. At the meantime, the monocyte membrane-coated nanoparticle shows the capability of tumor-tropism. These results indicate that the monocyte membrane-coated nanoparticle has the therapeutic potential in cancer therapy, and it is worthwhile to further investigate on it.
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