氧化石墨烯奈米載體結合pH敏感探針以進行同步感測與pH應答之寡核苷酸藥物釋放模型

Abstract

氧化石墨烯 (graphene oxide, GO) 是一種二維的碳奈米材料，廣泛地運用在生物應用，例如：生物偵測器、組織工程、生物影像、以及藥物載體。在本論文中，我們設計一種利用GO當作藥物載體，並結合pH-sensitive的螢光染劑 (rhodamine dye)來當作追蹤藥物的藥物釋放模型。我們合成出一系列不同氧化程度的GO，將模擬藥物－poly-dT30修飾在GO上，並評估其在不同pH值的環境下的穩定度以及poly-dT30與pH-sensitive的rhodamine dye競爭吸附GO的反應。所合成之rhodamine dye在酸性環境下會發出紅色螢光 (ex= 561 nm, em= 588 nm)，然而一旦吸附在GO上，其螢光會淬息 (quench)，同時poly-dT30也會被競爭下來。我們發現氧化程度較高的GO較適合作為此模型之藥物載體。目前的研究結果顯示，我們建立的藥物釋放模型在未來應具潛力運用在癌組織等較酸環境中RNAi的傳送及釋放。

Graphene oxide (GO), 2-D structure of carbon nanomaterial, has been used in several bio-applications, such as biosensor, tissue engineering, bio-imaging, and drug delivery. Herein, we constructed a GO-based nanocarrier combined with the pH sensitive fluorescence tracer for both pH sensing and drug delivery. A series of GOs with different degree of oxidation were investigated to optimize the adsorption of model drug—poly-dT30. In our scheme, the pH-sensitive rhodamine dye was first applied for cellular pH monitoring. Under acidic environment, protonated rhodamine dye emits fluorescence at 588 nm (ex= 561 nm). The rhodamine dye-triggerd competition reaction occurred when the dT30-GO nanocarrier was introduced, leading to the release of oligonucleotide and quench the fluorescence of rhodamine dye by GO. We found more oxidized GO is better candidate for drug carrier in vitro. Current results have indicated its potential for targeted RNAi delivery in acidic tumor milieu.