第五章 結果與討論
5.7 PLGNP-TPP 活化細胞自噬
細胞中針對粒線體受損有一套處理的機制，受損的粒線體會被細胞自噬清除 以維持細胞內整體粒線體的正常功能。69因此接下來我們觀察細胞自噬活化的現象 是否會在和PLGNP-TPP 共培養後的 A549 細胞中產生。我們以兩種方法觀察細胞 自噬是否增加，第一種是酸性胞器染色，第二種是觀察細胞自噬的marker ，即 LC3 的表現。酸性胞器的染劑使用的是 acridine orange，在酸性胞器內會呈現紅色，
在細胞質呈現綠色。這是一個初步判別細胞自噬產生的autophagosome 有沒有增加 的方法，但無法排除其他酸性胞器如lysosome 的影響，結果如圖十九(a)。結果顯 示PLGNP-TPP 1nM 共培養 12 小時候 A549 細胞中的酸性胞器似乎有增多。以西 方點墨法觀察LC3 的表現，我們發現，與 PLGNP-TPP 共培養後的細胞有活化細 胞自噬的現象。LC3 在正常情況下在細胞質內，但細胞自噬被活化後會和
autophagosome 上的 phosphatidylethanolamine conjugate 在一起93，即圖十九(b) 中 標示的LC3II。觀察細胞自噬的 marker LC3 的表現後我們發現，與 PLGNP-TPP 共 培養後的細胞有活化細胞自噬的現象。
56
圖 十九：PLGNP-TPP 活化細胞自噬(a)酸性胞器染色結果，(b)細胞自噬 maker LC3 western blot 結果
(a)
(b)
57 實驗的PLGNP-TPP。下一步將會使癌細胞與 PLGNP-TPP 共培養後，分離出粒線 體並用ICP-MS 評估其進入到粒線體的效率。若 ICP-MS 測得的數據證明
PLGNP-TPP 可以有效地進入到粒線體，則此修飾策略將可應用到其他不同種類的 奈米藥物載體上。
本研究也嘗試利用有無粒線體標靶分子修飾之PLGNP 來闡明金奈米粒子對粒
線體功能的影響。在細胞存活率試驗(MTT assay)發現 PLGNP-TPP 會影響 A549 肺 癌細胞的存活率，進一步測試和粒線體活性有關的指標，發現細胞中的ATP level
58
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