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標題: | 氧化鐵奈米粒子之生物醫學效應以及應用 Application and biomedical effects of iron oxide nanoparticles |
作者: | Jong-Kai Hsiao 蕭仲凱 |
指導教授: | 王兆麟(Jaw-Lin Wang) |
關鍵字: | 超順磁氧化鐵,奈米粒子,幹細胞,巨噬細胞,磁振造影, superparamagnetic iron oxide,nanoparticle,magnetic resonance imaging,stem cells,macrophage, |
出版年 : | 2008 |
學位: | 博士 |
摘要: | 氧化鐵奈米粒子是最近十幾年開發出來的磁振造影對比劑,具有超順磁以及奈米的物理特性,其化學組成為氧化鐵的核心加上外層包覆可分解的高分子用來增加水溶性以及懸浮性.在臨床的使用上可以用來標示肝臟內的網狀內皮細胞以及身體其他部位的巨噬細胞,作為肝臟腫瘤的偵測以及鑑別診斷的工具.由於氧化鐵奈米粒子是少數可以應用於臨床的奈米粒子,因此其生物特性特別令人感到好奇.因此我們對於氧化鐵奈米粒子與巨噬細胞的交互作用,細胞激素,吞噬能力等進行了一系列的分析以及探討.
當巨噬細胞將氧化鐵奈米粒子吞噬之後,我們在光學顯微鏡以及電子顯微鏡下發現,這些氧化鐵奈米粒子分布在細胞質的溶小體中,這個發現與其他研究的結果相符.同時巨噬細胞在吞噬大量的氧化鐵奈米粒子之後,其吞噬作用的能力有下降的情形產生,同時其分泌腫瘤壞死因子,一氧化氮的能力上升,這些現象代表了氧化鐵奈米粒子會影響到巨噬細胞的生理功能,我們並且發現了這些生理功能的變化,都是在巨噬細胞培養在濃度為一百微克�毫升的氧化鐵奈米粒子溶液中,由於巨噬細胞同時在冠狀動脈硬化,腫瘤的轉移等疾病現象中扮演重要的角色,因此是否可利用我們發現的現象,進行巨噬細胞的調節,則有待更進一步的探討. 幹細胞在組織工程上扮演舉足輕重的角色,因為其具有分化以及增生的能力,因此被認為具有修補受傷組織,作為器官移植等醫療用途.在文獻上也有許多的報告將幹細胞用於治療心肌梗塞,腦部疾病等.由於直接將幹細胞植入生物體內,我們無法清楚的了解這些幹細胞是否停留在原先的組織上,或是經由循環等路徑到達其他器官,因此有些研究學者利用氧化鐵奈米粒子將幹細胞進行標示,在磁振造影上用來追蹤幹細胞在生物體內的分布. 我們利用臨床上之氧化鐵奈米粒子Ferucarbotran 來進行幹細胞標示,發現Ferucarbotran可以直接用來標示幹細胞,不需要加入其他的藥物,並且這種標示方法可以達到相當高的細胞內氧化鐵濃度,在這種標示狀況下,幹細胞並沒有活性上的改變,粒線體的電位差也沒有變化,同時幹細胞的骨骼以及脂肪組織的分化能力都沒有受到改變.藉由我們的標示方法,我們順利的在臨床使用的磁振造影儀下進行掃描,可以清晰的看到單一細胞的影像.因此我們相信這種幹細胞標示的方式將可以用來進行幹細胞的活體追蹤. Superparamagnetic iron oxide nanoparticles have been used as clinical magnetic resonance imaging contrast agents. They are composed of iron oxide core coated with biodegradable polymers such as dextran or carboxydextran for improving solubility and suspensibility. Once if they are delivered into human body, most of them will be ingested by circulating macrophages and reticulo-endothelial system that mostly resides in the liver. Clinically, they are used for detecting and differentiating hepatic tumors. Although certain percentages of these particles are ingested by macrophages, little is known about the physiological influence of these particles after ingested into cells. We evaluated the physiological functions of macrophages including phagocytic activity, cellular migration, tumor necrosis factor-alpha(TNF-α) secretion, interleukin-1 beta (IL-1β) and nitric oxide excretions. There is decreased phagocytic activity but increased cell migration ability. The cytokine assays showed increased TNF-αand IL-1β secretion. There is also increase in nitric oxide secretion after nanoparticles ingestion. We conclude that macrophage physiological functions are altered after magnetic iron oxide nanoparticles ingestion. The impact on the whole living organism should be further investigated. Stem cells play important roles in the development of tissue engineering. It is proposed that stem cells could be used for tissue repair and organ transplantation. The magnetic iron oxide nanoparticles have been used for labeling of stem cells for visualizing the fate of the cells in living organisms. Most of the labeling techniques are achieved by incorporation with transfecting agents such as protamine sulfate. We developed a simple method by choosing one kind of magnetic iron oxide nanoparticles, Ferucarbotran that has carboxydextran coating instead of dextran coating. This method is simple and the viability, mitochondrial membrane potential, and reactive oxygen species are not altered. Moreover, the capacity of osteocyte and adipocyte differentiation is preserved. We evaluated the efficacy of labeling ability by visualizing the cells at 1.5 Tesla clinical magnetic resonance imaging system and up to single cells could be resolved. We conclude that this labeling method is efficacious and could be applied in the stem cell technology. In summery, the superparamagnetic iron oxide nanoparticles have different biological and medical application than materials at different size. Further evaluation of the impact of these particles on the biomedical science is beneficial in the development of nanotechnology and stem cell therapy. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37261 |
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顯示於系所單位: | 醫學工程學研究所 |
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