量子點奈米粒子具有穩定的螢光性質，因此許多量子點(quantum dots, QDs) 被研究如何應用在藥物運輸和生物醫學影像上，未來可進一步探討量子點應用於肺部的藥物運輸或肺部顯影之可能性，但是必須先評估其安全性及生物相容性。QD705是ㄧ種以金屬鎘為主要成分的量子點，本論文目的是評估QD705對小鼠肺臟的生物反應(包括生物相容度和分解情形)，探討修飾聚乙二醇(PEG, Polyethylene Glycols)是否能降低QD705所引起之生物反應；再進一步利用細胞株探討QD705造成之生物效應的機制。首先，在小鼠實驗部分，經由氣管灌注60 g QD705-COOH一次，不論是在17和90天後，都會持續誘發大量嗜中性球累積於肺組織，進而伴隨肺泡間質發生淋巴球浸潤和肉芽腫(granuloma)等病變。小鼠暴露QD705-COOH 17天後，其肺組織中多種細胞激素、化學激素和金屬蛋白酶12 表現增加，小鼠的肺功能變差:而暴露QD705-PEG 17天的小鼠肺臟也發生類似病變及生物反應，不同的是在暴露90天之後，雖然發炎反應持續發生，但肉芽腫大部分已消失。以上結果顯示，QD705s會造成肺部嚴重的發炎反應且修飾聚乙二醇的量子點無法防止發炎反應。不論暴露QD705-COOH或 QD705-PEG，在90天內都仍以螢光顯微鏡觀察到量子點的螢光，顯示量子點未完全消失；進一步定量組織內量子點主要金屬成份鎘與銻，發現肺組織內鎘與銻濃度隨時間而下降，而鎘與銻濃度比例隨時間而上升，暗示量子點在肺組織逐漸被排除且已發生解離。
接著，我們以在小鼠巨噬細胞(RAW264.7)為模式，探討量子點引起肺臟急性發炎之機轉。在小鼠巨噬細胞(RAW264.7)中QD705-COOH和QD705-PEG會經由MyD88 dependent Toll-like receptor (TLR)訊息路徑活化NF¬-B增加 monocyte chemotactic protein-1 (MCP-1)的表現量。MCP-1是一種化學激素，會誘發大量的巨噬細胞和單核球到發炎的部位。MyD88是大部分Toll-like receptors (TLRs)的訊息銜接子(adaptors)，能進一步活化NF¬-B。以siRNA方式抑制MyD88和p65的表現，或共同處理NF¬-B抑制劑，都會抑制量子點(QD705s)活化NF¬-B和誘發MCP-1表現。TLRs分為兩大類: ㄧ類是分佈在細胞表面(例如TLR4)；另一類則是分佈於細胞內的胞器上。共同處理TLR4抑制劑完全抑制QD705-PEG所誘發MCP-1的表現；但相反地，卻只抑制少部分QD705-COOH所誘發MCP-1的表現。進一步我們觀察到QD705-COOH會進入到細胞中，而共同處理內吞作用(endocytosis)或細胞內胞器上TLRs的抑制劑後，可以抑制QD705-COOH所誘發MCP-1的表現。根據上述結果得知，QD705s依據不同的表現修飾，會在細胞表面或細胞內活化MyD88 dependent Toll-like receptor (TLR)訊息路徑，其訊息路徑是量子點奈米粒子誘發發炎反應的主要機制。
從本篇研究得知，氣管罐注量子點會使小鼠肺組織產生嚴重的發炎反應，大量巨噬細胞在肺組織浸潤，進而誘發許多與發炎相關基因增加，造成肉芽腫形成；可能因為量子點在巨噬細胞會經由活化MyD88 dependent Toll-like receptor (TLR)訊息路徑，活化NF¬-B進而，增加促進發炎的基因表現。因此QD705無法應用於肺部顯影或作為吸入性藥物之載體。這本篇研究中我們建立 奈米醫藥相關產品安全性評估的模式，包含奈米粒子在物理化學特性品質控制(Quality Control, QC)的分析檢測項目，以及未來能提供經由肺部暴露奈米粒子安全評估的方法建立，而協助將來奈米醫學產業發展。

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