Reversible Targeting and controlled release delivery of daunorubicin to cancer cells by aptamer-wrapped carbon nanotubes
Reversible Targeting and controlled release delivery of daunorubicin to cancer cells by aptamer-wrapped carbon nanotubes
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DOI：
10.1016/j.ejpb.2010.12.005
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发表时间：
2011-02-01
影响因子：
4.9
通讯作者：
Abnous, Khalil
中科院分区：
文献类型：
--
作者：
Taghdisi, Seyed Mohammad;Lavaee, Parirokh;Abnous, Khalil
目的：单壁碳纳米管（SWNT）已被用作药物载体。在本研究中，我们将 sgc8c 适体（该适体靶向白血病生物标志物蛋白酪氨酸激酶 7）引入 Dau（柔红霉素）和 SWNT 之间的复合物，以增强 Dau 向急性淋巴细胞白血病 T 细胞（Molt-4）的靶向递送。材料和方法：通过可见光谱和荧光分光光度分析分析 Dau-适体-SWNT 三级复合物的形成。在 pH 7.4 和 5.5 条件下研究了复合物的 Dau 释放曲线。对于细胞毒性研究（MTT 测定），Molt-4（靶标）和 U266（B 淋巴细胞人骨髓瘤，非靶标）细胞用 Dau、Dau-适体-SWNT 三级复合物处理。通过流式细胞术分析内化。使用适体反义来拮抗 Dau 的靶向递送。结果：Dau 被有效负载到 SWNT 上（效率类似于 157%）。 Dau 以 pH 依赖性方式从 Daauaptamer-SWNTs 三级复合物中释放（pH 5.5 时释放速率较高）。流式细胞分析表明，三级复合物被 Molt-4 细胞有效内化，但 U266 细胞则不然。 Dau-适体-SWNT 三级复合物的细胞毒性也证实了内化数据。与单独的 Dau 相比，Dau-适体-SWNT 三级复合物在 U266 细胞中的细胞毒性较低。未观察到 Dau 和复合物处理的 Molt-4 细胞的活力发生显着变化。在Molt-4细胞中使用反义核酸可以有效、快速地逆转Dau-适体-SWNTs复合物的细胞毒性。结论：Dau-适体-SWNTs复合物能够选择性地靶向Molt-4细胞。该系统的其他优点是 Dau 从其复合物中的可逆性和 pH 依赖性释放。 (C) 2010 Elsevier B.V. 保留所有权利。
Aim: Single-walled carbon nanotubes (SWNTs) have been already used as drug carriers. In this study, we introduced sgc8c aptamer (this aptamer targets leukemia biomarker protein tyrosine kinase-7) to complex between Dau (daunorubicin) and SWNT to enhance targeted delivery of Dau to acute lymphoblastic leukemia T-cells (Molt-4).Material and methods: Dau-aptamer-SWNTs tertiary complex formation was analyzed by visible spectroscopy and spectrofluorophotometric analysis. Dau release profiles from the complex were investigated in pH 7.4 and 5.5. For cytotoxic studies (MTT assay), Molt-4 (target) and U266 (B lymphocyte human myeloma, non-target) cells were treated with Dau, Dau-aptamer-SWNTs tertiary complex. Internalization was analyzed by flow cytometry. Targeted delivery of Dau was antagonized using antisense of aptamer.Results : Dau was efficiently loaded onto SWNTs (efficiency similar to 157%). Dau was released from Dauaptamer-SWNTs tertiary complex in a pH-dependent manner (higher release rate at pH 5.5). Flow cytometric analysis showed that the tertiary complex was internalized effectively to Molt-4 cells, but not to U266 cells. Cytotoxicity of Dau-aptamer-SWNTs tertiary complex also confirmed internalization data. Dau-aptamer-SWNTs tertiary complex was less cytotoxic in U266 cells when compared to Dau alone. No significant change in viability between Dau- and complex-treated Molt-4 cells was observed. Cytotoxicity of Dau-aptamer-SWNTs complex was efficiently and quickly reversed using antisense in Molt-4 cells.Conclusion: Dau-aptamer-SWNTs complex is able to selectively target Molt-4 cells. The other advantages of this system are reversibility and pH-dependant release of Dau from its complex. (C) 2010 Elsevier B.V. All rights reserved.