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Title: 製備矽藻土二氧化矽奈米粒子並具備雙重靶向及控制釋放之藥物遞送系統
Preparation of Diatomite Silica Nanoparticles with Dual-Target and Control Release for the Drug Delivery System
Authors: Lee, Hsing-Chun
Contributors: 國立臺灣海洋大學:生命科學暨生物科技學系
Keywords: 矽藻土;矽藻土二氧化矽奈米粒子;雙標靶分子;藥物控制釋放
diatomite;diatomite silica nanoparticles;dual-target;drug control release system
Date: 2017
Issue Date: 2018-08-22T06:31:27Z
Abstract: 近年來,來自海洋資源再利用的矽藻土可說是現今熱門的研究指標。矽藻土(diatomite)為一種天然沉積的多孔性二氧化矽,由於它是天然且環保,以及具有良好的生物相容性,因此很有潛力被能當成一種新穎的藥物載體DSN(diatomite silica nanoparticles)。本研究是以物理研磨的方式將矽藻土奈米化,並將奈米化的矽藻土進行熱酸處理,去除掉表面的有機無機雜質。接著透過化學修飾的方式在DSN表面嫁接上雙重標靶分子葉酸及葡萄糖分子,讓具有雙重靶向的DSN能對癌細胞更具專一性,達到增強藥物遞送的效果。 本篇的藥物釋放機制是使用雙硫鍵(disulfide bond)作為控制藥物釋放的開關,並且把抗癌藥物喜樹鹼(CPT)嫁接在雙硫鍵上。透過細胞內外穀胱甘肽(Glutathione)的濃度差異讓雙硫鍵在細胞內容易因為高濃度的穀胱甘肽而讓雙硫鍵斷鍵,進而釋放藥物;而在細胞外穀胱甘肽濃度低時雙硫鍵不易斷鍵,讓藥物不會提前從載體上釋放,進而達到可控制的藥物釋放。 最後,本研究將雙硫鍵控制藥物釋放開關和雙標靶藥物遞送系統結合在新穎的材料DSN上並嫁接上螢光分子FITC,利用雷射共軛焦顯微鏡觀察材料進入到細胞的情況。綜合以上,期望DSN能成為另一種節能且環保的二氧化矽藥物載體。
In recent years, diatomite from ocean resources reuse can be a hot research index. Diatomite is a natural porous biomaterial of sedimentary origin. Due to its good Biocompatibility and non-toxicity, thus suggesting their potentiality as nanocarriers for drug delivery, DSN (diatomite silica nanoparticles). In this study, we preparation DSN by physical grinding, and DSN was subjected to thermal acid treatment to remove the organic and inorganic impurities on the surface. Then we functionalized of grafted double-labeled molecules, folic acid and glucose targeted molecules on DSN surface. So that a dual-targeting DSN can be more specific combination of cancer cells, to enhance the effectiveness of drug delivery. In this study we use the disulfide bonds as a switch to control drug release, and to graft the anticancer drug camptothecin (CPT) on a disulfide bond. Then use Intracellular and extracellular glutathione different concentration to controlled drug release, in the intracellular, a high concentration of glutathione disulfide bond environment will stimulate the bond cleaves, the drug molecules release; extracellular glutathione concentration than the low, disulfide bond wont early broken. So that the drug is not released from the carrier in advance, the achieving controlled drug release. At last, the drug-releasing switch and double-target drug delivery system were combined with the novel material DSN and grafted with fluorescent molecules FITC, then we use confocal to observed DSN into cell, we hope DSN can be another Substitute nanocarriers of silica drug delivery system.
URI: http://ethesys.lib.ntou.edu.tw/cgi-bin/gs32/gsweb.cgi?o=dstdcdr&s=G001043B016.id
Appears in Collections:[生命科學暨生物科技學系] 博碩士論文

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