†Department of Applied Chemistry, ‡Center for Interdisciplinary Science (CIS), and §Institute of Molecular Science, National Chiao-Tung University, No. 1001 Ta-Hsueh Road, Hsinchu 30010, Taiwan.
ACS Appl Mater Interfaces. 2015 Jun 3;7(21):11467-75. doi: 10.1021/acsami.5b02397. Epub 2015 May 18.
We chemically tuned the oxidation status of graphene oxide (GO) and constructed a GO-based nanoplatform combined with a pH-sensitive fluorescence tracer that is designed for both pH sensing and pH-responsive drug delivery. A series of GOs oxidized to distinct degrees were examined to optimize the adsorption of the model drug, poly dT30. We determined that highly oxidized GO was a superior drug-carrier candidate in vitro when compared to GOs oxidized to lesser degrees. In the cell experiment, the synthesized pH-sensitive rhodamine dye was first applied to monitor cellular pH; under acidic conditions, protonated rhodamine fluoresces at 588 nm (λex=561 nm). When the dT30-GO nanocarrier was introduced into cells, a rhodamine-triggered competition reaction occurred, and this led to the release of the oligonucleotides and the quenching of rhodamine fluorescence by GO. Our results indicate high drug loading (FAM-dT30/GO=25/50 μg/mL) and rapid cellular uptake (<0.5 h) of the nanocarrier which can potentially be used for targeted RNAi delivery to the acidic milieu of tumors.
我们通过化学方法调节氧化石墨烯（GO）的氧化状态，并构建了一个基于 GO 的纳米平台，结合了一种 pH 敏感的荧光示踪剂，用于 pH 传感和 pH 响应药物输送。我们考察了一系列氧化程度不同的 GO，以优化模型药物聚 dT30 的吸附。与氧化程度较低的 GO 相比，我们发现高度氧化的 GO 是体外更优的药物载体候选物。在细胞实验中，我们首先将合成的 pH 敏感的罗丹明染料用于监测细胞 pH；在酸性条件下，质子化的罗丹明在 588nm 处发荧光（λex=561nm）。当 dT30-GO 纳米载体被引入细胞时，罗丹明引发竞争反应，导致寡核苷酸的释放和 GO 对罗丹明荧光的猝灭。我们的结果表明，纳米载体具有高药物载量（FAM-dT30/GO=25/50μg/mL）和快速的细胞摄取（<0.5h），可用于靶向 RNAi 递送到肿瘤的酸性环境中。
